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  • 301.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, s. E18-E18Artikel i tidskrift (Övrigt vetenskapligt)
  • 302.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    van Bavel, Bert
    Salihovic, Samira
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating Levels of Persistent Organic Pollutants (POPs) and Carotid Atherosclerosis in the Elderly2012Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 120, nr 1, s. 38-43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective:

    Increased circulating levels of persistent organic pollutants (POPs) have been associated with myocardial infarction. Because myocardial infarction is an atherosclerotic disease, we investigated, in a cross-sectional study, whether POP levels are related to atherosclerosis.

    Methods:

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1,016 participants 70 years of age), the prevalence of carotid artery plaques was determined by ultrasound. The number of carotid arteries with plaques (0, 1, or 2) was recorded. Also, the intima-media thickness (IMT) and gray scale median of the intima-media complex (IM-GSM) were measured. Twenty-three POPs, comprising 16 polychlorinated biphenyls (PCBs), 5 pesticides, 1 dioxin, and 1 brominated compound (brominated diphenyl ether congener BDE-47), were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry.

    Results:

    Seven of the POPs (PCB congeners 153, 156, 157, 170, 180, 206, and 209) were significantly associated with the number of carotid arteries with plaques even after adjusting for multiple risk factors (sex, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, high-density lipoprotein and low-density lipoprotein cholesterol, serum triglycerides, smoking, antihypertensive treatment, and statin use; p = 0.002-0.0001). Highly chlorinated PCBs (congeners 194, 206, and 209) were associated with an echolucent IM-GSM (p < 0.0001 after adjustment), whereas associations between POPs and IMT were modest.

    Conclusions:

    Circulating levels of PCBs were associated with atherosclerotic plaques and echogenicity of the intima-media complex independent of cardiovascular risk factors, including lipids. This suggests that POPs may be a risk factor for myocardial infarction, but associations need to be confirmed in prospective studies.

  • 303. Lind, Monica
    et al.
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Edlund, Ulla-Britt
    Sjöblom, Linnea
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    The dioxin-like pollutant PCB 126 (3,3',4,4',5-pentachlorobiphenyl) affects risk factors for cardiovascular disease in female rats2004Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 150, nr 3, s. 293-299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies suggest that exposure to persistent organic pollutants such as organochlorines might induce cardiovascular disorders and diabetes. Some of these organochlorines, such as dioxins and some dioxin-like PCBs, have been characterised as anti-estrogenic due to their inhibition of estrogenic-induced responses. In the present pilot study, 40 female rats were subjected to either exposure to the dioxin-like 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or vehicle, as well as ovariectomy (OVX) or sham operation in a 2 x 2 factorial design over 12 weeks to explore potential interactions between estrogen status and PCB 126 exposure on cardiovascular risk factors. PCB 126 increased heart weight and serum cholesterol levels in both groups. PCB 126 increased blood pressure in the sham-operated animals only. In conclusion, PCB 126 exposure in female rats resulted in effects on cardiovascular risk factors, such as serum cholesterol, blood pressure, and heart weight. Of these effects of PCB 126, the increase in blood pressure was dependent on estrogen status.

  • 304.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 7, s. 1495-1502Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The purpose of this study was to review the epidemiological and experimental evidence linking background exposure to a selection of environmental endocrine-disrupting chemicals (EDCs) with diabetes and impaired glucose metabolism. The review summarises the literature on both cross-sectional and prospective studies in humans, as well as experimental in vivo and in vitro studies. The findings were subjected to evidence grading according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. We found > 40 cross-sectional and seven prospective studies regarding EDCs and risk of diabetes. Taken together, there is moderate evidence for a relationship between exposure to dichlorodiphenyldichloroethylene (p,p'-DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane, and diabetes development. Regarding polychlorinated biphenyls (PCBs), it is likely that the rodent models used are not appropriate, and therefore the evidence is poorer than for p,p'-DDE. For other EDCs, such as bisphenol A, phthalates and perfluorinated chemicals, the evidence is scarce, since very few prospective studies exist. Brominated flame retardants do not seem to be associated with a disturbed glucose tolerance. Thus, evidence is accumulating that EDCs might be involved in diabetes development. Best evidence exists for p,p'-DDE. For other chemicals, both prospective studies and supporting animal data are still lacking.

  • 305.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    An environmental wide association study (EWAS) approach to the metabolic syndrome2013Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 55, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Environmental contaminants have previously been linked to components of the Metabolic Syndrome (MetS). However, exposure to environmental contaminants is in part determined by various lifestyle factors. Objective: Using an "Environmental Wide Association Study" (ELWAS) integrating environmental contaminants and lifestyle factors, we aimed to evaluate a possible additive role of both contaminants and lifestyle factors regarding MetS. Methods: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. 43 environmental contaminants were measured in the circulation. Dietary records were used to evaluate 21 nutrients and the proportions of 13 fatty acids were determined in serum cholesterol esters to further quantify fat quality intake. Adding 5 other important lifestyle factors yielded together 76 environmental and lifestyle factors. MetS was defined by the NCEP/ATPIII-criteria. Results: 23% had MetS. Using cross-validation within the sample, fourteen environmental contaminants or lifestyle factors consistently showed a false discovery rate <0.05. When the major variables entered a multiple model, only p,p'-DDE levels (positive), PCB209 (inverse) and exercise habits (inverse) were together with a fatty acid pattern, with high levels of palmitic acid and oleic acid and low levels of linoleic acid, related to MetS (p<0.002 for all variables). Conclusion: Using a cross-sectional EWAS approach, certain environmental contaminants and lifestyle factors were found to be associated with prevalent metabolic syndrome in an additive fashion in an elderly population. 

  • 306.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Roos, Vendela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women2012Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 11, nr 1, s. 21-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.

    METHODS:

    1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.

    RESULTS:

    In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.

    CONCLUSIONS:

    The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

  • 307.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. MTM Research Center, School of Science and Technology, Örebro University, Örebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis2018Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, s. 109-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

    OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

    RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

    CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

  • 308.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Orebro Univ, Sch Med Sci, Inflammatory Response & Infect Susceptibil Ctr, Orebro, Sweden;Orebro Univ, Sch Sci & Technol, Man Technol Environm MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, Man Technol Environm MTM Res Ctr, Orebro, Sweden;Wellington Labs Inc, Guelph, ON, Canada.
    Karrman, Anna
    Orebro Univ, Sch Sci & Technol, Man Technol Environm MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study2019Ingår i: JAMA NETWORK OPEN, ISSN 2574-3805, Vol. 2, nr 4, artikel-id e193070Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE It has been suggested that persistent organic pollutants (POPs) are harmful to human health.

    OBJECTIVE To investigate if POP levels in plasma are associated with future mortality.

    DESIGN, SETTING, AND PARTICIPANTS Cohort study using data from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, collected between May 2001 and June 2004 when participants reached age 70 years. Participants were followed up for 5 years after the first examination. Mortality was tracked from age 70 to 80 years. Data analysis was conducted in January and February 2018.

    EXPOSURES Eighteen POPs identified by the Stockholm Convention, including polychlorinated biphenyls (PCBs), organochlorine pesticides, and a brominated flame retardant, were measured in plasma levels by gas chromatography-mass spectrometry.

    MAIN OUTCOMES AND MEASURES All-cause mortality.

    RESULTS The study sample initially included 992 individuals (497 [50.1%] men) aged 70 years, who were examined between 2001 and 2004. At the second examination 5 years later, 814 individuals (82.1%; 412 [50.7%] women) completed follow-up. During a follow-up period of 10.0 years, 158 deaths occurred. When updated information on POP levels at ages 70 and 75 years was associated with all-cause mortality using Cox proportional hazard analyses, a significant association was found between hexa-chloro-through octa-chloro-substituted (highly chlorinated) PCBs and all-cause mortality (except PCB 194). The most significant association was observed for PCB 206 (hazard ratio [HR] for 1-SD higher natural log-transformed circulating PCB 206 levels, 1.55; 95% CI, 1.26-1.91; P < .001). Following adjustment for hypertension, diabetes, smoking, body mass index, and cardiovascular disease at baseline, most associations were no longer statistically significant, but PCBs 206, 189, 170, and 209 were still significantly associated with all-cause mortality (PCB 206: adjusted HR, 1.47; 95% CI, 1.19-1.81; PCB 189: adjusted HR, 1.29; 95% CI, 1.08-1.55; PCB 170: adjusted HR, 1.24; 95% CI, 1.02-1.52; PCB 209: adjusted HR, 1.29; 95% CI, 1.04-1.60). In a secondary analysis, these associations were mainly because of death from cardiovascular diseases rather than noncardiovascular diseases. Three organochlorine pesticides, including dichlorodiphenyldichloroethylene, and the brominated flame retardant diphenyl ether 47 were also evaluated but did not show any significant associations with all-cause mortality.

    CONCLUSIONS AND RELEVANCE Higher levels of highly chlorinated PCBs were associated with an increased mortality risk, especially from cardiovascular diseases. These results suggest that public health actions should be undertaken to minimize exposure to highly chlorinated PCBs.

  • 309.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study2018Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, artikel-id 59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

    Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

    Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

  • 310.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis2017Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 152, s. 157-164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: During recent years, some persistent organic pollutants (POPs) have been linked to atherosclerosis. One group of POPs, the poly- and perfluoroalkyl substances (PFASs) have not been investigated with regard to atherosclerotic plaques.

    METHODS: Carotid artery atherosclerosis was assessed by ultrasound in 1016 subjects aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants' plasma by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    RESULTS: No significant linear associations were observed between the PFASs and intima-media thickness (IMT), or the echogenicity in the intima-media complex (IM-GSM, a marker of lipid infiltration in the artery) when men and women were analyzed together. Neither was occurrence of carotid plaques related to PFASs levels. However, highly significant interactions were observed between some PFASs and sex regarding both IM-GSM and plaque prevalence. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were all related to IM-GSM in a positive fashion in women (p=0.002-0.003), while these relationships were negative in men. The levels of PFUnDA were significantly related to carotid plaque in women (OR 1.59, 95%CI 1.03-2.43, p=0.03), but not in men (OR 0.93, 95%CI 0.62-1.42, p=0.75).

    CONCLUSIONS: In this cross-sectional study, a pronounced gender difference was observed regarding associations between some PFASs, especially the long-chain PFUnDA, and markers of atherosclerosis, with more pronounced relationships found in women. These findings suggest a sex-specific role for PFASs in atherosclerosis.

  • 311.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly2012Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, nr 7, s. 1519-1524Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE-Phthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator activated receptors (PPARs). Because PPAR-gamma agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L. RESULTS-A total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin to insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance. CONCLUSIONS-The findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.

  • 312. Lind, Ylva Sjoberg
    et al.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly2013Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 123, s. 39-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: Major risk factors for congestive heart failure (CHF) are myocardial infarction, hypertension, diabetes, atrial fibrillation, smoking, left ventricular hypertrophy (LVH) and obesity. However, since these risk factors only explain part of the risk of CHF, we investigated whether persistent organic pollutants (POPs) might also play a role. Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, left ventricular ejection fraction, (EF), E/A-ratio and isovolumic relaxation time (IVRT), were determined by echocardiography and serum samples of 21 POPs were analyzed in serum measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 998 subjects all aged 70 years. Results: In this cross-sectional analysis, high levels of several of the polychlorinated biphenyls (PCB congeners 99, 118, 105, 138, 153, and 180) and octachlorodibenzo-p-dioxin (OCDD) were significantly related to a decreased EF. Some POPs were also related to a decreased E/A-ratio (PCBs 206 and 209). All the results were adjusted for gender, hypertension, diabetes, smoking, LVH and BMI, and subjects with myocardial infarction or atrial fibrillation were excluded from the analysis. Conclusions: Circulating levels of POPs were related to impairments in both left ventricular systolic and diastolic function independently of major congestive heart failure risk factors, suggesting a possible role of POPs in heart failure.

  • 313. Lind, Ylva Sjoeberg
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    van Bavel, Bert
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Persistent organic pollutants and abnormal geometry of the left ventricle in the elderly2013Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 8, s. 1547-1553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    Established risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes, and obesity. However, as these risk factors explain only part of the variation in left ventricular mass, we investigated whether persistent organic pollutants (POPs) might also play a role in LVH, because exposure to polychlorinated biphenyl 126 induced cardiac growth in rats.

    Methods:

    In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), left ventricular mass index (LVMI), relative wall thickness (RWT), and geometric groups of LVH, were determined by echocardiography and 21 POPs were measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 1016 individuals aged 70 years. All individuals with a history of myocardial infarction were excluded from analysis (n=72).

    Results:

    Several of the POPs were related to abnormal left ventricular geometry before adjustment for established risk factors, but lost in significance following adjustment. However, the pesticide hexachlorobenzene (HCB) levels were significantly related to RWT, and concentric left ventricular remodeling, also following adjustment for sex, blood pressure, antihypertensive treatment, diabetes, and BMI (P<0.0001).

    Conclusion:

    In this cross-sectional study, circulating levels of HCB were related to increased wall thickness of the left ventricle and concentric left ventricular remodeling, independently of LVH risk factors, suggesting a role of this environmental contaminant in abnormal growth of the left ventricle.

  • 314. Lindgren, Karin
    et al.
    Hagelin, Elin
    Hansen, Niclas
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance.2006Ingår i: J Hypertens: Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance, ISSN 0263-6352, Vol. 24, nr 1, s. 143-50Artikel i tidskrift (Övrigt vetenskapligt)
  • 315. Liu, C
    et al.
    Marioni, R E
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pfeiffer, L
    Tsai, P-C
    Reynolds, L M
    Just, A C
    Duan, Q
    Boer, C G
    Tanaka, T
    Elks, C E
    Aslibekyan, S
    Brody, J A
    Kühnel, B
    Herder, C
    Almli, L M
    Zhi, D
    Wang, Y
    Huan, T
    Yao, C
    Mendelson, M M
    Joehanes, R
    Liang, L
    Love, S-A
    Guan, W
    Shah, S
    McRae, A F
    Kretschmer, A
    Prokisch, H
    Strauch, K
    Peters, A
    Visscher, P M
    Wray, N R
    Guo, X
    Wiggins, K L
    Smith, A K
    Binder, E B
    Ressler, K J
    Irvin, M R
    Absher, D M
    Hernandez, D
    Ferrucci, L
    Bandinelli, S
    Lohman, K
    Ding, J
    Trevisi, L
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Stolk, L
    Uitterlinden, A G
    Yet, I
    Castillo-Fernandez, J E
    Spector, T D
    Schwartz, J D
    Vokonas, P
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Li, Y
    Fornage, M
    Arnett, D K
    Wareham, N J
    Sotoodehnia, N
    Ong, K K
    van Meurs, J B J
    Conneely, K N
    Baccarelli, A A
    Deary, I J
    Bell, J T
    North, K E
    Liu, Y
    Waldenberger, M
    London, S J
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Levy, D
    A DNA methylation biomarker of alcohol consumption.2018Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, s. 422-433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

  • 316.
    Ljunggren, S. A.
    et al.
    Linkoping Univ, Occupat & Environm Med Ctr, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Iggland, M.
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Karlsson, H.
    Linkoping Univ, Occupat & Environm Med Ctr, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Altered heart proteome in fructose-fed Fisher 344 rats exposed to bisphenol A2016Ingår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 347-349, s. 6-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bisphenol A (BPA), is an artificial estrogen initially produced for medical purposes but is today widely used in polycarbonate plastics and epoxy resins. Exposure-related reproductive disorders have been found, but recently it has also been suggested that BPA may be involved in obesity, diabetes, myocardial hypertrophy and myocardial infarction in humans. To mimic a modern lifestyle, female rats were fed with fructose or fructose plus BPA (0.25 mg/L drinking water). The myocardial left ventricle proteome of water controls, fructose-fed and fructose-fed plus BPA supplemented rats was explored. The proteome was investigated using nano-liquid chromatography tandem mass spectrometry and two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization mass spectrometry identification. In total, 41 proteins were significantly altered by BPA exposure compared to water or fructose controls. Principal component analysis and cellular process enrichment analysis of altered proteins suggested increased fatty acid transport and oxidation, increased ROS generation and altered structural integrity of the myocardial left ventricle in the fructose-fed BPA-exposed rats, indicating unfavorable effects on the myocardium. In conclusion, BPA exposure in the rats induces major alterations in the myocardial proteome.

  • 317. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L
    Yang, Jian
    Croteau-Chonka, Damien C
    Esko, Tonu
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ferreira, Teresa
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Mägi, Reedik
    Randall, Joshua C
    Winkler, Thomas W
    Wood, Andrew R
    Workalemahu, Tsegaselassie
    Faul, Jessica D
    Smith, Jennifer A
    Hua Zhao, Jing
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Karjalainen, Juha
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Medland, Sarah E
    Nalls, Michael A
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Shungin, Dmitry
    Stančáková, Alena
    Strawbridge, Rona J
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Attwood, Antony P
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Blagieva, Roza
    Blüher, Matthias
    Böhringer, Stefan
    Bonnycastle, Lori L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Caspersen, Ida H
    Ida Chen, Yii-Der
    Clarke, Robert
    Warwick Daw, E
    de Craen, Anton J M
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S F
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Goodall, Alison H
    Gordon, Scott D
    Gorski, Mathias
    Grabe, Hans-Jörgen
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    Groves, Christopher J
    Gusto, Gaëlle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L
    Jeff, Janina M
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindström, Jaana
    Sin Lo, Ken
    Lobbens, Stéphane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Nagaraja, Ramaiah
    Nöthen, Markus M
    Nolte, Ilja M
    Pilz, Stefan
    Rayner, Nigel W
    Renstrom, Frida
    Rettig, Rainer
    Ried, Janina S
    Ripke, Stephan
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Scott, William R
    Seufferlein, Thomas
    Shi, Jianxin
    Vernon Smith, Albert
    Smolonska, Joanna
    Stanton, Alice V
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tan, Sian-Tsung
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Warren, Helen R
    Waterworth, Dawn
    Weedon, Michael N
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Brennan, Eoin P
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W
    Eriksson, Per
    Franco-Cereceda, Anders
    Gådin, Jesper R
    Gharavi, Ali G
    Goddard, Michael E
    Handsaker, Robert E
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McCarroll, Steven A
    McKnight, Amy J
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Okada, Yukinori
    Perry, John R B
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Scott, Robert A
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    Van't Hooft, Ferdinand M
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T
    Heath, Andrew C
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I
    Chines, Peter S
    Collins, Francis S
    Crawford, Dana C
    Adrienne Cupples, L
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Dominiczak, Anna F
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Felix, Stephan B
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Homuth, Georg
    Kees Hovingh, G
    Humphries, Steve E
    Hunt, Steven C
    Hyppönen, Elina
    Illig, Thomas
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jöckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Wouter Jukema, J
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Knekt, Paul
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Moll, Frans L
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Madden, Pamela A F
    Pasterkamp, Gerard
    Peden, John F
    Peters, Annette
    Postma, Dirkje S
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Rioux, John D
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schunkert, Heribert
    Schwarz, Peter E H
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Trégouët, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Willemsen, Gonneke
    Witteman, Jacqueline C
    Zillikens, M Carola
    Adair, Linda S
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E
    Schlessinger, David
    Eline Slagboom, P
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Weir, David R
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Heid, Iris M
    O'Connell, Jeffrey R
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    Franke, Lude
    Frayling, Timothy M
    McCarthy, Mark I
    Visscher, Peter M
    Scherag, André
    Willer, Cristen J
    Boehnke, Michael
    Mohlke, Karen L
    Lindgren, Cecilia M
    Beckmann, Jacques S
    Barroso, Inês
    North, Kari E
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hirschhorn, Joel N
    Loos, Ruth J F
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 197-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 318.
    Lorenz, Matthias W.
    et al.
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Gao, Lu
    Univ Forvie Site, MRC, Biostat Unit, Inst Publ Hlth, Cambridge, England..
    Ziegelbauer, Kathrin
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Norata, Giuseppe Danilo
    Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.;Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy..
    Empana, Jean Philippe
    Univ Paris 05, Sorbonne Paris Cite, UMR, Paris Cardiovasc Res Ctr PARCC, Paris, France..
    Schmidtmann, Irene
    Univ Med Mainz, IMBEI, Mainz, Germany..
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    McLachlan, Stela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Bokemark, Lena
    Gothenburg Univ, Sahlgrenska Acad, Dept Mol & Clin Med, Wallenberg Lab Cardiovasc Res,Inst Medicin, Gothenburg, Sweden..
    Ronkainen, Kimmo
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Amato, Mauro
    IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Schminke, Ulf
    Greifswald Univ Clin, Dept Neurol, Greifswald, Germany..
    Srinivasan, Sathanur R.
    Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Cardiovasc Hlth, Dept Epidemiol,Biochem, New Orleans, LA USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Okazaki, Shuhei
    Osaka Univ, Grad Sch Med, Dept Neurol, Osaka, Japan..
    Stehouwer, Coen D. A.
    Maastricht Univ, Med Ctr, Dept Internal Med, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands..
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.;Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Steinmetz, Helmuth
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Sander, Dirk
    Benedictus Hosp Tutzing & Feldafing, Dept Neurol, Feldafing, Germany..
    Poppert, Holger
    Tech Univ Munich, Dept Neurol, Munich, Germany..
    Desvarieux, Moise
    Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA..
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands..
    Johnsen, Stein Harald
    Uit, Dept Clin Med, Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol, Tromso, Norway..
    Staub, Daniel
    Univ Basel Hosp, Dept Angiol, Basel, Switzerland..
    Sirtori, Cesare R.
    Osped Niguarda Ca Granda, Ctr Dyslipidemias, Milan, Italy..
    Igiseder, Bernhard
    Parcelsus Med Univ, Salzburg, Austria.;Gemeinnutzige Salzburger Landeskliniken Betriebsg, Doppler Klin, Dept Geriatr Med, Salzburg, Austria..
    Beloqui, Oscar
    Univ Navarra Clin, Dept Internal Med, Navarra, Spain..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Friera, Alfonso
    Univ Autonoma Madrid, Hosp Univ La Princesa, Dept Radiol, Madrid, Spain..
    Rozza, Francesco
    Univ Naples Federico II, Sch Med, Naples, Italy..
    Xie, Wuxiang
    Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Parraga, Grace
    Western Univ, Roberts Res Inst, London, ON, Canada..
    Grigore, Liliana
    Bassini Hosp, Ctr Sisa Studio Aterosclerosi, Cinisello Balsamo, Italy..
    Plichart, Matthieu
    Hop Broca, AP HP, Paris, France..
    Blankenberg, Stefan
    Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.;Univ Hosp Hamburg Eppendorf, Dept Cardiol, Hamburg, Germany..
    Su, Ta-Chen
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    Schmidt, Caroline
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Voelzke, Henry
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Inst Community Med, SHIP Clin Epidemiol Res, Greifswald, Germany..
    Nijpels, Giel
    Vrije Univ Amsterdam, Dept Gen Practice, Medial Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Uthoff, Heiko
    Univ Basel Hosp, Dept Angiol, Basel, Switzerland..
    Hedblad, Bo
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Suarez, Carmen
    Univ Autonoma Madrid, Hosp Univ La Princesa, Dept Internal Med, Madrid, Spain..
    Izzo, Raffaele
    Univ Naples Federico II, Sch Med, Naples, Italy..
    Zhao, Dong
    Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Wannarong, Thapat
    Western Univ, Stroke Prevent & Atherosclerosis Res Ctr, Roberts Res Inst, London, ON, Canada.;Mahidol Univ, Dept Internal Med, Fac Med, Siriraj Hosp, Bangkok, Thailand..
    Catapano, Alberico
    IRCSS Multimed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Ducimetiere, Pierre
    Univ Paris Sud Xi, Le Kremlin Bicetre, France..
    Espinola-Klein, Christine
    Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany..
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan..
    Price, Jackie F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Bergstrom, Goren
    Gothenburg Univ, Wallenberg Lab Cardiovasc Res, Sahlgrenska Acad, Gotheborg, Sweden..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Tremoli, Elena
    Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany..
    Berenson, Gerald
    Tulane Univ, Sch Med, Dept Med, Pediat,Biochem,Epidemiol, 1430 Tulane Ave, New Orleans, LA 70112 USA.;Sch Publ Hlth & Trop Med, New Orleans, LA USA..
    Kitagawa, Kazuo
    Tokyo Womens Med Univ, Dept Neurol, Tokyo, Japan..
    Dekker, Jacqueline M.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Sitzer, Matthias
    Klinikum Herford, Dept Neuol, Herford, Germany..
    Bickel, Horst
    Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Mathiesen, Ellisiv B.
    Uit, Dept Clin Med, Tromso, Norway..
    Castelnuovo, Samuela
    Osped Niguarda Ca Granda, Ctr Dyslipidemias, Milan, Italy..
    Landecho, Manuel F.
    Univ Navarra Clin, Dept Internal Med, Navarra, Spain..
    Rosvall, Maria
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Gabriel, Rafael
    Inst Salud Carlos III, Escuela Natl Sanidad, Madrid, Spain..
    de Luca, Nicola
    Univ Naples Federico II, Sch Med, Naples, Italy..
    Liu, Jing
    Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands..
    de Groot, Eric
    Imagelabonline & Cardiovasc, Eindhoven, Netherlands.;Imagelabonline & Cardiovasc, Lunteren, Netherlands.;Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Yanez, David N.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Thompson, Simon G.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0191172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

    Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.

    Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

  • 319. Lorenz, Matthias W.
    et al.
    Polak, Joseph F.
    Kavousi, Maryam
    Mathiesen, Ellisiv B.
    Voelzke, Henry
    Tuomainen, Tomi-Pekka
    Sander, Dirk
    Plichart, Matthieu
    Catapano, Alberico L.
    Robertson, Christine M.
    Kiechl, Stefan
    Rundek, Tatjana
    Desvarieux, Moise
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Schmid, Caroline
    DasMahapatra, Pronabesh
    Gao, Lu
    Ziegelbauer, Kathrin
    Bots, Michiel L.
    Thompson, Simon G.
    Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data2012Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 379, nr 9831, s. 2053-2062Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association.

    Methods: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis.

    Findings: Of 21 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7.0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0.97 (95% CI 0.94-1.00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0.98 (0.95-1.01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1.16, 95% CI 1.10-1.22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0.06 and r=-0.02).

    Interpretation: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.

  • 320.
    Lorenz, Matthias W.
    et al.
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Price, Jackie F.
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Robertson, Christine
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Poppert, Holger
    Tech Univ Munich, Univ Hosp, Dept Neurol, D-80290 Munich, Germany..
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Doerr, Marcus
    Greifswald Univ Clin, Dept Internal Med Cardiol B, Greifswald, Germany..
    Stensland, Eva
    Univ Tromso, Dept Clin Med, Tromso, Norway..
    Ducimetiere, Pierre
    Univ Paris 11, Paris, France..
    Ronkainen, Kimmo
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria..
    Sitzer, Matthias
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany.;Klinikum Herford, Dept Neurol, Herford, Germany..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Jing
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Bergstrom, Goran
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Grigore, Liliana
    Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy.;IRCCS MultiMed, Milan, Italy..
    Bokemark, Lena
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Friera, Alfonsa
    Univ Autonoma Madrid, Hosp Univ la Princesa, Dept Radiol, Madrid, Spain..
    Yanez, David
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Bickel, Horst
    Tech Univ Munich, Univ Hosp, Dept Psychiat, D-80290 Munich, Germany..
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Voelzke, Henry
    Ernst Moritz Arndt Univ Greifswald, SHIP Clin Epidemiol Res, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res, Greifswald, Germany..
    Johnsen, Stein Harald
    Univ Tromso, Dept Clin Med, Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol & Neurophysiol, Tromso, Norway..
    Empana, Jean Philippe
    INSERM U970, Paris, France..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Steinmetz, Helmuth
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Desvarieux, Moise
    Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.;Ecole Hautes Etud Sante Publ, Paris, France.;INSERM U738, Paris, France..
    Xie, Wuxiang
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Schmidt, Caroline
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Norata, Giuseppe D.
    Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Suarez, Carmen
    Univ Autonoma Madrid, Hosp Univ la Princesa, Dept Internal Med, Madrid, Spain..
    Sander, Dirk
    Tech Univ Munich, Univ Hosp, Dept Neurol, D-80290 Munich, Germany.;Benedictus Hosp Tutzing & Feldafing, Dept Neurol, Feldafing, Germany..
    Hofman, Albert
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Schminke, Ulf
    Greifswald Univ Clin, Dept Neurol, Greifswald, Germany..
    Mathiesen, Ellisiv
    Univ Tromso, Dept Clin Med, Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol & Neurophysiol, Tromso, Norway..
    Plichart, Matthieu
    INSERM U970, Paris, France.;Broca Hosp, Gerontol Dept, Paris, France..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    McLachlan, Stela
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Zhao, Dong
    Inst Heart Lung & Blood Vessel Dis, Dept Epidemiol, Beijing, Peoples R China..
    Fagerberg, Bjorn
    Univ Gothenburg, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden..
    Catapano, Alberico L.
    IRCCS MultiMed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Gabriel, Rafael
    Univ Autonoma Madrid, Hosp Univ La Paz, Inst Invest IdiPAZ, Madrid, Spain..
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Buelbuel, Alpaslan
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Scheckenbach, Frank
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Pflug, Anja
    Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany..
    Gao, Lu
    Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England..
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration2015Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, nr 10, s. 1921-1929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

  • 321. Loth, Daan W
    et al.
    Artigas, María Soler
    Gharib, Sina A
    Wain, Louise V
    Franceschini, Nora
    Koch, Beate
    Pottinger, Tess D
    Smith, Albert Vernon
    Duan, Qing
    Oldmeadow, Chris
    Lee, Mi Kyeong
    Strachan, David P
    James, Alan L
    Huffman, Jennifer E
    Vitart, Veronique
    Ramasamy, Adaikalavan
    Wareham, Nicholas J
    Kaprio, Jaakko
    Wang, Xin-Qun
    Trochet, Holly
    Kähönen, Mika
    Flexeder, Claudia
    Albrecht, Eva
    Lopez, Lorna M
    de Jong, Kim
    Thyagarajan, Bharat
    Alves, Alexessander Couto
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Omenaas, Ernst
    Joshi, Peter K
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Viñuela, Ana
    Launer, Lenore J
    Loehr, Laura R
    Fornage, Myriam
    Li, Guo
    Wilk, Jemma B
    Tang, Wenbo
    Manichaikul, Ani
    Lahousse, Lies
    Harris, Tamara B
    North, Kari E
    Rudnicka, Alicja R
    Hui, Jennie
    Gu, Xiangjun
    Lumley, Thomas
    Wright, Alan F
    Hastie, Nicholas D
    Campbell, Susan
    Kumar, Rajesh
    Pin, Isabelle
    Scott, Robert A
    Pietiläinen, Kirsi H
    Surakka, Ida
    Liu, Yongmei
    Holliday, Elizabeth G
    Schulz, Holger
    Heinrich, Joachim
    Davies, Gail
    Vonk, Judith M
    Wojczynski, Mary
    Pouta, Anneli
    Johansson, Åsa
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wild, Sarah H
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rivadeneira, Fernando
    Völzke, Henry
    Hysi, Pirro G
    Eiriksdottir, Gudny
    Morrison, Alanna C
    Rotter, Jerome I
    Gao, Wei
    Postma, Dirkje S
    White, Wendy B
    Rich, Stephen S
    Hofman, Albert
    Aspelund, Thor
    Couper, David
    Smith, Lewis J
    Psaty, Bruce M
    Lohman, Kurt
    Burchard, Esteban G
    Uitterlinden, André G
    Garcia, Melissa
    Joubert, Bonnie R
    McArdle, Wendy L
    Musk, A Bill
    Hansel, Nadia
    Heckbert, Susan R
    Zgaga, Lina
    van Meurs, Joyce B J
    Navarro, Pau
    Rudan, Igor
    Oh, Yeon-Mok
    Redline, Susan
    Jarvis, Deborah L
    Zhao, Jing Hua
    Rantanen, Taina
    O'Connor, George T
    Ripatti, Samuli
    Scott, Rodney J
    Karrasch, Stefan
    Grallert, Harald
    Gaddis, Nathan C
    Starr, John M
    Wijmenga, Cisca
    Minster, Ryan L
    Lederer, David J
    Pekkanen, Juha
    Gyllensten, Ulf
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Campbell, Harry
    Morris, Andrew P
    Gläser, Sven
    Hammond, Christopher J
    Burkart, Kristin M
    Beilby, John
    Kritchevsky, Stephen B
    Gudnason, Vilmundur
    Hancock, Dana B
    Williams, O Dale
    Polasek, Ozren
    Zemunik, Tatijana
    Kolcic, Ivana
    Petrini, Marcy F
    Wjst, Matthias
    Kim, Woo Jin
    Porteous, David J
    Scotland, Generation
    Smith, Blair H
    Viljanen, Anne
    Heliövaara, Markku
    Attia, John R
    Sayers, Ian
    Hampel, Regina
    Gieger, Christian
    Deary, Ian J
    Boezen, H Marike
    Newman, Anne
    Jarvelin, Marjo-Riitta
    Wilson, James F
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Stricker, Bruno H
    Teumer, Alexander
    Spector, Timothy D
    Melén, Erik
    Peters, Marjolein J
    Lange, Leslie A
    Barr, R Graham
    Bracke, Ken R
    Verhamme, Fien M
    Sung, Joohon
    Hiemstra, Pieter S
    Cassano, Patricia A
    Sood, Akshay
    Hayward, Caroline
    Dupuis, Josée
    Hall, Ian P
    Brusselle, Guy G
    Tobin, Martin D
    London, Stephanie J
    Genome-wide association analysis identifies six new loci associated with forced vital capacity2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, s. 669-677Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

  • 322. Lu, Yingchang
    et al.
    Day, Felix R
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Buchkovich, Martin L
    Na, Jianbo
    Bataille, Veronique
    Cousminer, Diana L
    Dastani, Zari
    Drong, Alexander W
    Esko, Tõnu
    Evans, David M
    Falchi, Mario
    Feitosa, Mary F
    Ferreira, Teresa
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Haring, Robin
    Hysi, Pirro G
    Iles, Mark M
    Justice, Anne E
    Kanoni, Stavroula
    Lagou, Vasiliki
    Li, Rui
    Li, Xin
    Locke, Adam
    Lu, Chen
    Mägi, Reedik
    Perry, John R B
    Pers, Tune H
    Qi, Qibin
    Sanna, Marianna
    Schmidt, Ellen M
    Scott, William R
    Shungin, Dmitry
    Teumer, Alexander
    Vinkhuyzen, Anna A E
    Walker, Ryan W
    Westra, Harm-Jan
    Zhang, Mingfeng
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Zhihong
    Afzal, Uzma
    Ahluwalia, Tarunveer Singh
    Bakker, Stephan J L
    Bellis, Claire
    Bonnefond, Amélie
    Borodulin, Katja
    Buchman, Aron S
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Choh, Audrey C
    Choi, Hyung Jin
    Curran, Joanne E
    de Groot, Lisette C P G M
    De Jager, Philip L
    Dhonukshe-Rutten, Rosalie A M
    Enneman, Anke W
    Eury, Elodie
    Evans, Daniel S
    Forsen, Tom
    Friedrich, Nele
    Fumeron, Frédéric
    Garcia, Melissa E
    Gärtner, Simone
    Han, Bok-Ghee
    Havulinna, Aki S
    Hayward, Caroline
    Hernandez, Dena
    Hillege, Hans
    Ittermann, Till
    Kent, Jack W
    Kolcic, Ivana
    Laatikainen, Tiina
    Lahti, Jari
    Mateo Leach, Irene
    Lee, Christine G
    Lee, Jong-Young
    Liu, Tian
    Liu, Youfang
    Lobbens, Stéphane
    Loh, Marie
    Lyytikäinen, Leo-Pekka
    Medina-Gomez, Carolina
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nalls, Mike A
    Nielson, Carrie M
    Oozageer, Laticia
    Pascoe, Laura
    Paternoster, Lavinia
    Polašek, Ozren
    Ripatti, Samuli
    Sarzynski, Mark A
    Shin, Chan Soo
    Narančić, Nina Smolej
    Spira, Dominik
    Srikanth, Priya
    Steinhagen-Thiessen, Elisabeth
    Sung, Yun Ju
    Swart, Karin M A
    Taittonen, Leena
    Tanaka, Toshiko
    Tikkanen, Emmi
    van der Velde, Nathalie
    van Schoor, Natasja M
    Verweij, Niek
    Wright, Alan F
    Yu, Lei
    Zmuda, Joseph M
    Eklund, Niina
    Forrester, Terrence
    Grarup, Niels
    Jackson, Anne U
    Kristiansson, Kati
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Lichtner, Peter
    Luan, Jian'an
    Mahajan, Anubha
    Männistö, Satu
    Palmer, Cameron D
    Ried, Janina S
    Scott, Robert A
    Stancáková, Alena
    Wagner, Peter J
    Demirkan, Ayse
    Döring, Angela
    Gudnason, Vilmundur
    Kiel, Douglas P
    Kühnel, Brigitte
    Mangino, Massimo
    Mcknight, Barbara
    Menni, Cristina
    O'Connell, Jeffrey R
    Oostra, Ben A
    Shuldiner, Alan R
    Song, Kijoung
    Vandenput, Liesbeth
    van Duijn, Cornelia M
    Vollenweider, Peter
    White, Charles C
    Boehnke, Michael
    Boettcher, Yvonne
    Cooper, Richard S
    Forouhi, Nita G
    Gieger, Christian
    Grallert, Harald
    Hingorani, Aroon
    Jørgensen, Torben
    Jousilahti, Pekka
    Kivimaki, Mika
    Kumari, Meena
    Laakso, Markku
    Langenberg, Claudia
    Linneberg, Allan
    Luke, Amy
    Mckenzie, Colin A
    Palotie, Aarno
    Pedersen, Oluf
    Peters, Annette
    Strauch, Konstantin
    Tayo, Bamidele O
    Wareham, Nicholas J
    Bennett, David A
    Bertram, Lars
    Blangero, John
    Blüher, Matthias
    Bouchard, Claude
    Campbell, Harry
    Cho, Nam H
    Cummings, Steven R
    Czerwinski, Stefan A
    Demuth, Ilja
    Eckardt, Rahel
    Eriksson, Johan G
    Ferrucci, Luigi
    Franco, Oscar H
    Froguel, Philippe
    Gansevoort, Ron T
    Hansen, Torben
    Harris, Tamara B
    Hastie, Nicholas
    Heliövaara, Markku
    Hofman, Albert
    Jordan, Joanne M
    Jula, Antti
    Kähönen, Mika
    Kajantie, Eero
    Knekt, Paul B
    Koskinen, Seppo
    Kovacs, Peter
    Lehtimäki, Terho
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Yongmei
    Orwoll, Eric S
    Osmond, Clive
    Perola, Markus
    Pérusse, Louis
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Rivadeneira, Fernando
    Rudan, Igor
    Salomaa, Veikko
    Sørensen, Thorkild I A
    Stumvoll, Michael
    Tönjes, Anke
    Towne, Bradford
    Tranah, Gregory J
    Tremblay, Angelo
    Uitterlinden, André G
    van der Harst, Pim
    Vartiainen, Erkki
    Viikari, Jorma S
    Vitart, Veronique
    Vohl, Marie-Claude
    Völzke, Henry
    Walker, Mark
    Wallaschofski, Henri
    Wild, Sarah
    Wilson, James F
    Yengo, Loïc
    Bishop, D Timothy
    Borecki, Ingrid B
    Chambers, John C
    Cupples, L Adrienne
    Dehghan, Abbas
    Deloukas, Panos
    Fatemifar, Ghazaleh
    Fox, Caroline
    Furey, Terrence S
    Franke, Lude
    Han, Jiali
    Hunter, David J
    Karjalainen, Juha
    Karpe, Fredrik
    Kaplan, Robert C
    Kooner, Jaspal S
    McCarthy, Mark I
    Murabito, Joanne M
    Morris, Andrew P
    Bishop, Julia A N
    North, Kari E
    Ohlsson, Claes
    Ong, Ken K
    Prokopenko, Inga
    Richards, J Brent
    Schadt, Eric E
    Spector, Tim D
    Widén, Elisabeth
    Willer, Cristen J
    Yang, Jian
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Mohlke, Karen L
    Hirschhorn, Joel N
    Pospisilik, John Andrew
    Zillikens, M Carola
    Lindgren, Cecilia
    Kilpeläinen, Tuomas Oskari
    Loos, Ruth J F
    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk2016Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikel-id 10495Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

  • 323.
    Lundberg, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    A comparison between different indices of carotid artery atherosclerosis at ultrasound regarding risk of incident myocardial infarction and stroke2015Artikel i tidskrift (Övrigt vetenskapligt)
  • 324.
    Lundberg, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi. AstraZeneca R&D, Mölndal, Sweden.
    The relationship between carotid intima-media thickness and global atherosclerosis2014Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, nr 6, s. 457-462Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to investigate the relationship between (i) carotid intima-media thickness (CIMT) at baseline as well as (ii) change in CIMT over 5 years (ΔCIMT) and atherosclerotically induced luminal narrowing in non-coronary arterial territories assessed by whole-body magnetic resonance angiography (WBMRA).

    METHODS AND RESULTS:

    In subgroups of the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) study, US measurements of CIMT in the common carotid arteries were analysed at 70 and 75 years and ΔCIMT was calculated (n = 272). WBMRA, assessing arterial stenosis in five different territories by which also a total atherosclerotic score (TAS) was calculated, was performed at 70 years (n = 306).

    RESULTS:

    Carotid intima-media thickness in the carotid artery at baseline was correlated with TAS (P = 0·0001) when adjusted to a set of traditional risk factors for atherosclerosis, as well as to stenosis in two of the different investigated territories (aorta and lower leg, P = 0·013 and P = 0·004), but there was no significant correlation between ΔCIMT and TAS (P = 0·41).

    CONCLUSIONS:

    In the present study, CIMT, but not ΔCIMT over 5 years, in the carotid artery was related to overall stenoses in the body, as assessed by WBMRA. These findings support CIMT as a general marker for atherosclerosis.

  • 325.
    Lundberg, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ebeling Barbier, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, nr 1, s. 148-152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE.

    METHODS AND RESULTS:

    305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421).

    CONCLUSION:

    In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

  • 326.
    Lundgren, E
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lind, L
    Institutionen för medicinska vetenskaper.
    Palmer, M
    Jakobsson, S
    Ljunghall, S
    Institutionen för medicinska vetenskaper.
    Rastad, J
    Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years.2001Ingår i: Surgery, ISSN 0039-6060, Vol. 130, nr 6, s. 978-85Artikel i tidskrift (Refereegranskat)
  • 327. Luttropp, Karin
    et al.
    Nordfors, Louise
    Ekstrom, Tomas J.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Physical activity is associated with decreased global DNA methylation in Swedish older individuals2013Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, nr 2, s. 184-185Artikel i tidskrift (Refereegranskat)
  • 328.
    Lytsy, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Interplay of overweight and insulin resistance on hypertension development2014Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, nr 4, s. 834-839Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Obesity and hypertension are associated, possibly through causal pathways involving insulin resistance and metabolic derangements. We aimed to investigate in a whites sample if overweight or obese persons without insulin resistance are at risk of developing hypertension or blood pressure progression. Methods: In a meta-analysis, using multivariable-adjusted mixed-effects logistic regression models, we investigated the risks of hypertension development and blood pressure progression by combinations of relative weight classes and presence or absence of insulin resistance (defined as highest vs. lower three quartiles using the homeostatic model assessment method) in the Uppsala Longitudinal Study of Adult Men (n = 2322) and the Prospective Investigation of the Vasculature in Uppsala Seniors studies (n = 1066). These two samples, consisting mainly of middle-aged and elderly men, provided 1846 observations for the development of hypertension in normotensive individuals and 4223 observations for progressing to a higher blood pressure stage. Results: During a median of 10 years of follow-up, 884 (47.9%) developed hypertension and 1639 (38.8%) progressed to a higher blood pressure stage. Overweight or obese persons without insulin resistance had an increased risk of hypertension development [odds ratio (OR) 1.46, 95% confidence interval 1.14-1.88] and blood pressure progression (OR 1.32, 1.10-1.59) compared with normal-weight persons without insulin resistance. Conclusion: According to this study, being overweight or obese without insulin resistance increases the risk of hypertension and blood pressure progression. This adds to the evidence that overweight and obesity may be harmful per se, and that overweight and obesity without glucometabolic derangements are not benign conditions.

  • 329.
    Lytsy, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Endothelial function and risk of hypertension and blood pressure progression: the prospective investigation of the vasculature in Uppsala seniors2013Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 5, s. 936-939Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES

    Impaired endothelial function is associated with risk of cardiovascular events, possibly via increased blood pressure. We aimed to investigate if impaired endothelial function is associated with risk of hypertension and blood pressure progression in a large community-based sample.

    METHODS

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, endothelium-dependent vasodilation (EDV) was measured in resistance arteries using the invasive forearm technique and in conduit arteries using the flow-mediated vasodilation technique (FMD) at age 70, and participants were re-examined after 5 years. We investigated risk of developing hypertension or blood pressure progression in multivariable-adjusted logistic regression models.

    RESULTS

    In 201 out of 506 untreated persons, blood pressure progressed to a higher stage, and among 197 normotensive persons, 87 developed hypertension. Endothelial function, measured with the invasive forearm technique and the brachial ultrasound technique, did not predict either the development of hypertension [EDV: odds ratio (OR) per SD 1.16, 95% confidence interval (CI) 0.84-1.59; FMD: OR per SD 1.00, 95% CI 0.76-1.33) or blood pressure progression (EDV: OR per SD 0.90, 95% CI 0.73-1.11; FMD: OR per SD 1.01, 95% CI 0.84-1.21).

    CONCLUSION

    In this large community-based sample of elderly, impaired endothelial function measured with the invasive forearm technique did not play a major role in the development of hypertension or blood pressure progression. Observed associations between endothelial dysfunction and risk of cardiovascular events are likely mediated through other pathways than hypertension.

  • 330. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 13230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

  • 331. Maggio, Marcello
    et al.
    Cattabiani, Chiara
    Lauretani, Fulvio
    Mantovani, Marco
    Butto, Valeria
    De Vita, Francesca
    Volpi, Riccardo
    Artoni, Andrea
    Giallauria, Francesco
    Zuliani, Giovanni
    Aloe, Rosalia
    Lippi, Giuseppe
    Ceresini, Graziano
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ceda, Gian Paolo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    SHBG and endothelial function in older subjects2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, nr 3, s. 2825-2830Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Endothelial dysfunction is predictor of cardiovascular diseases that have different prevalence in men and women before menopause. Sex hormones and sex hormone binding globulin (SHBG), novel risk factors for diabetes and cardiovascular diseases even in older individuals, might explain this difference. However, the relationship between these hormones and endothelial function has never been addressed in the elderly. Methods and results: 430 men and, 424 women 70 years older of Prospective Study of the Vasculature in Uppsala Seniors study, with complete data on SHBG, testosterone(T), estradiol(E2), endothelium-independent vasodilation (EIDV), endothelium-dependent vasodilation(EDV), flow-mediated vasodilation (FMD) and the pulse wave analysis (reflection index, RI) were evaluated. Multivariate regression analysis adjusted for confounders was used to assess the relationship between T, E2, SHBG and endothelial function. In men we found a positive relationship between SHBG and EDV (beta +/- SE 3.60 +/- 0.83, p < 0.0001), EIDV (2.42 +/- 0.58, p < 0.0001) but not with FMD. The relationship between SHBG and EDV and EIDV was maintained after adjustment for sex (1.64 +/- 0.47, p < 0.001 and 1.79 +/- 0.35, p < 0.0006, respectively). After adjustment for confounders, the relationship between SHBG and EDV and EIDV was still statistically significant (2.63 +/- 0.90 and 1.86 +/- 0.63, p = 0.004 for both). In women SHBG and EIDV were positively associated (1.58 +/- 0.46; p = 0.0007), and this relationship was independent of sex (1.79 +/- 0.35; p < 0.001). No significant interaction SHBG * SEX was found for EIDV (p = 0.72). In a combined analysis in two sexes, SHBG and EIDV were positively associated (1.13 +/- 0.45; p = 0.01). SHBG was not associated with EDV, FMD and RI. No significant relationship was found between T or E2 and EDV, EIDV, FMD or RI in both sexes. Conclusions: In older men SHBG, but not T and E2, is positively and independently associated with EDV in resistance arteries. In both sexes, SHBG was positively and independently associated with EIDV.

  • 332. Maggio, Marcello
    et al.
    De Vita, Francesca
    Lauretani, Fulvio
    Ceda, Gian Paolo
    Volpi, Elena
    Giallauria, Francesco
    De Cicco, Giuseppe
    Cattabiani, Chiara
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Vitamin D and Endothelial Vasodilation in Older Individuals: Data From the PIVUS Study2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 9, s. 3382-3389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT:

    Vitamin D plays a role in a wide range of extraskeletal processes, including vascular function. Endothelial dysfunction is a predictor of cardiovascular disease, especially in older subjects. However, the relationship between vitamin D levels and indexes of endothelial vasodilation has never been fully addressed in older individuals.

    OBJECTIVE:

    The objective of this study was to examine the association between vitamin D and endothelial function in a large community-based sample of older subjects.

    METHODS:

    This cross-sectional study involved 852 community-dwelling men and women aged 70 years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), with complete data on vascular function and 25-hydroxyvitamin D. We evaluated endothelium-dependent vasodilation by an invasive forearm technique with acetylcholine, endothelium-independent vasodilation by sodium nitroprussiate, flow-mediated vasodilation, and the pulse wave analysis (reflectance index). Vitamin D levels were measured by chemiluminescence. We used multivariate regression models adjusted for body mass index (model 1) and for multiple confounders (high-sensitivity C-reactive protein, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, smoking, sex hormones, season of blood collection, hypertension, diabetes, cardiovascular medications and diseases, statin usage, plasma calcium and calcium intake, PTH, physical exercise, liver and kidney function tests, albumin; model 2).

    RESULTS:

    In women, but not in men, vitamin D levels were positively associated with endothelium-independent vasodilation in both model 1 (β ± SE = 1.41 ± 0.54; P = .001), and model 2 (β ± SE = 2.01 ± 0.68; P = .003).We found no significant relationship between vitamin D levels and endothelium-dependent vasodilation, flow-mediated vasodilation, and reflectance index in both sexes.

    CONCLUSIONS:

    In older women, but not in men, vitamin D is positively and independently associated with EIDV.

  • 333. Mahajan, Anubha
    et al.
    Go, Min Jin
    Zhang, Weihua
    Below, Jennifer E
    Gaulton, Kyle J
    Ferreira, Teresa
    Horikoshi, Momoko
    Johnson, Andrew D
    Ng, Maggie C Y
    Prokopenko, Inga
    Saleheen, Danish
    Wang, Xu
    Zeggini, Eleftheria
    Abecasis, Goncalo R
    Adair, Linda S
    Almgren, Peter
    Atalay, Mustafa
    Aung, Tin
    Baldassarre, Damiano
    Balkau, Beverley
    Bao, Yuqian
    Barnett, Anthony H
    Barroso, Ines
    Basit, Abdul
    Been, Latonya F
    Beilby, John
    Bell, Graeme I
    Benediktsson, Rafn
    Bergman, Richard N
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Burtt, Noel
    Cai, Qiuyin
    Campbell, Harry
    Carey, Jason
    Cauchi, Stephane
    Caulfield, Mark
    Chan, Juliana C N
    Chang, Li-Ching
    Chang, Tien-Jyun
    Chang, Yi-Cheng
    Charpentier, Guillaume
    Chen, Chien-Hsiun
    Chen, Han
    Chen, Yuan-Tsong
    Chia, Kee-Seng
    Chidambaram, Manickam
    Chines, Peter S
    Cho, Nam H
    Cho, Young Min
    Chuang, Lee-Ming
    Collins, Francis S
    Cornelis, Marilyn C
    Couper, David J
    Crenshaw, Andrew T
    van Dam, Rob M
    Danesh, John
    Das, Debashish
    de Faire, Ulf
    Dedoussis, George
    Deloukas, Panos
    Dimas, Antigone S
    Dina, Christian
    Doney, Alex S F
    Donnelly, Peter J
    Dorkhan, Mozhgan
    van Duijn, Cornelia
    Dupuis, Josee
    Edkins, Sarah
    Elliott, Paul
    Emilsson, Valur
    Erbel, Raimund
    Eriksson, Johan G
    Escobedo, Jorge
    Esko, Tonu
    Eury, Elodie
    Florez, Jose C
    Fontanillas, Pierre
    Forouhi, Nita G
    Forsen, Tom
    Fox, Caroline
    Fraser, Ross M
    Frayling, Timothy M
    Froguel, Philippe
    Frossard, Philippe
    Gao, Yutang
    Gertow, Karl
    Gieger, Christian
    Gigante, Bruna
    Grallert, Harald
    Grant, George B
    Groop, Leif C
    Groves, Christopher J
    Grundberg, Elin
    Guiducci, Candace
    Hamsten, Anders
    Han, Bok-Ghee
    Hara, Kazuo
    Hassanali, Neelam
    Hattersley, Andrew T
    Hayward, Caroline
    Hedman, Asa K
    Herder, Christian
    Hofman, Albert
    Holmen, Oddgeir L
    Hovingh, Kees
    Hreidarsson, Astradur B
    Hu, Cheng
    Hu, Frank B
    Hui, Jennie
    Humphries, Steve E
    Hunt, Sarah E
    Hunter, David J
    Hveem, Kristian
    Hydrie, Zafar I
    Ikegami, Hiroshi
    Illig, Thomas
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Islam, Muhammed
    Isomaa, Bo
    Jackson, Anne U
    Jafar, Tazeen
    James, Alan
    Jia, Weiping
    Jockel, Karl-Heinz
    Jonsson, Anna
    Jowett, Jeremy B M
    Kadowaki, Takashi
    Kang, Hyun Min
    Kanoni, Stavroula
    Kao, Wen Hong L
    Kathiresan, Sekar
    Kato, Norihiro
    Katulanda, Prasad
    Keinanen-Kiukaanniemi, Sirkka M
    Kelly, Ann M
    Khan, Hassan
    Khaw, Kay-Tee
    Khor, Chiea-Chuen
    Kim, Hyung-Lae
    Kim, Sangsoo
    Kim, Young Jin
    Kinnunen, Leena
    Klopp, Norman
    Kong, Augustine
    Korpi-Hyovalti, Eeva
    Kowlessur, Sudhir
    Kraft, Peter
    Kravic, Jasmina
    Kristensen, Malene M
    Krithika, S
    Kumar, Ashish
    Kumate, Jesus
    Kuusisto, Johanna
    Kwak, Soo Heon
    Laakso, Markku
    Lagou, Vasiliki
    Lakka, Timo A
    Langenberg, Claudia
    Langford, Cordelia
    Lawrence, Robert
    Leander, Karin
    Lee, Jen-Mai
    Lee, Nanette R
    Li, Man
    Li, Xinzhong
    Li, Yun
    Liang, Junbin
    Liju, Samuel
    Lim, Wei-Yen
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M
    Lindholm, Eero
    Liu, Ching-Ti
    Liu, Jian Jun
    Lobbens, Stephane
    Long, Jirong
    Loos, Ruth J F
    Lu, Wei
    Luan, Jian'an
    Lyssenko, Valeriya
    Ma, Ronald C W
    Maeda, Shiro
    Magi, Reedik
    Mannisto, Satu
    Matthews, David R
    Meigs, James B
    Melander, Olle
    Metspalu, Andres
    Meyer, Julia
    Mirza, Ghazala
    Mihailov, Evelin
    Moebus, Susanne
    Mohan, Viswanathan
    Mohlke, Karen L
    Morris, Andrew D
    Muhleisen, Thomas W
    Muller-Nurasyid, Martina
    Musk, Bill
    Nakamura, Jiro
    Nakashima, Eitaro
    Navarro, Pau
    Ng, Peng-Keat
    Nica, Alexandra C
    Nilsson, Peter M
    Njolstad, Inger
    Nothen, Markus M
    Ohnaka, Keizo
    Ong, Twee Hee
    Owen, Katharine R
    Palmer, Colin N A
    Pankow, James S
    Park, Kyong Soo
    Parkin, Melissa
    Pechlivanis, Sonali
    Pedersen, Nancy L
    Peltonen, Leena
    Perry, John R B
    Peters, Annette
    Pinidiyapathirage, Janani M
    Platou, Carl G P
    Potter, Simon
    Price, Jackie F
    Qi, Lu
    Radha, Venkatesan
    Rallidis, Loukianos
    Rasheed, Asif
    Rathmann, Wolfgang
    Rauramaa, Rainer
    Raychaudhuri, Soumya
    Rayner, N William
    Rees, Simon D
    Rehnberg, Emil
    Ripatti, Samuli
    Robertson, Neil
    Roden, Michael
    Rossin, Elizabeth J
    Rudan, Igor
    Rybin, Denis
    Saaristo, Timo E
    Salomaa, Veikko
    Saltevo, Juha
    Samuel, Maria
    Sanghera, Dharambir K
    Saramies, Jouko
    Scott, James
    Scott, Laura J
    Scott, Robert A
    Segre, Ayellet V
    Sehmi, Joban
    Sennblad, Bengt
    Shah, Nabi
    Shah, Sonia
    Shera, A Samad
    Shu, Xiao Ou
    Shuldiner, Alan R
    Sigurðsson, Gunnar
    Sijbrands, Eric
    Silveira, Angela
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S
    So, Wing Yee
    Stancakova, Alena
    Stefansson, Kari
    Steinbach, Gerald
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Strawbridge, Rona J
    Stringham, Heather M
    Sun, Qi
    Suo, Chen
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Takayanagi, Ryoichi
    Takeuchi, Fumihiko
    Tay, Wan Ting
    Teslovich, Tanya M
    Thorand, Barbara
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Tikkanen, Emmi
    Trakalo, Joseph
    Tremoli, Elena
    Trip, Mieke D
    Tsai, Fuu Jen
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Valladares-Salgado, Adan
    Vedantam, Sailaja
    Veglia, Fabrizio
    Voight, Benjamin F
    Wang, Congrong
    Wareham, Nicholas J
    Wennauer, Roman
    Wickremasinghe, Ananda R
    Wilsgaard, Tom
    Wilson, James F
    Wiltshire, Steven
    Winckler, Wendy
    Wong, Tien Yin
    Wood, Andrew R
    Wu, Jer-Yuarn
    Wu, Ying
    Yamamoto, Ken
    Yamauchi, Toshimasa
    Yang, Mingyu
    Yengo, Loic
    Yokota, Mitsuhiro
    Young, Robin
    Zabaneh, Delilah
    Zhang, Fan
    Zhang, Rong
    Zheng, Wei
    Zimmet, Paul Z
    Altshuler, David
    Bowden, Donald W
    Cho, Yoon Shin
    Cox, Nancy J
    Cruz, Miguel
    Hanis, Craig L
    Kooner, Jaspal
    Lee, Jong-Young
    Seielstad, Mark
    Teo, Yik Ying
    Boehnke, Michael
    Parra, Esteban J
    Chambers, John C
    Tai, E Shyong
    McCarthy, Mark I
    Morris, Andrew P
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 3, s. 234-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

  • 334.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Rodan, Aylin R.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Le, Thu H.
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Gaulton, Kyle J.
    Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
    Haessler, Jeffrey
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Stilp, Adrienne M.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Kamatani, Yoichiro
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Zhu, Gu
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Sofer, Tamar
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Puri, Sanjana
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Schellinger, Jeffrey N.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Chu, Pei-Lun
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Cechova, Sylvia
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    van Zuydam, Natalie
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. School of Health and Social Studies, Dalarna University, Falun 791 88, Sweden.
    Flessner, Michael F.
    National Institute of Diabetes, Digestive, and Kidney Disease, NIH, Bethesda, MD 20892, USA.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Heath, Andrew C.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Kubo, Michiaki
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK.
    Madden, Pamela A. F.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Montgomery, Grant W.
    Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Papanicolaou, George J.
    Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
    Reiner, Alex P.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Thornton, Timothy A.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
    Cai, Jianwen
    Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
    Martin, Nicholas G.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Kooperberg, Charles
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Matsuda, Koichi
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
    Whitfield, John B.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Okada, Yukinori
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
    Laurie, Cathy C.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
    Franceschini, Nora
    Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
    Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity2016Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, nr 3, s. 636-646Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

  • 335. Mahajan, Anubha
    et al.
    Sim, Xueling
    Ng, Hui Jin
    Manning, Alisa
    Rivas, Manuel A
    Highland, Heather M
    Locke, Adam E
    Grarup, Niels
    Im, Hae Kyung
    Cingolani, Pablo
    Flannick, Jason
    Fontanillas, Pierre
    Fuchsberger, Christian
    Gaulton, Kyle J
    Teslovich, Tanya M
    Rayner, N William
    Robertson, Neil R
    Beer, Nicola L
    Rundle, Jana K
    Bork-Jensen, Jette
    Ladenvall, Claes
    Blancher, Christine
    Buck, David
    Buck, Gemma
    Burtt, Noël P
    Gabriel, Stacey
    Gjesing, Anette P
    Groves, Christopher J
    Hollensted, Mette
    Huyghe, Jeroen R
    Jackson, Anne U
    Jun, Goo
    Justesen, Johanne Marie
    Mangino, Massimo
    Murphy, Jacquelyn
    Neville, Matt
    Onofrio, Robert
    Small, Kerrin S
    Stringham, Heather M
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Trakalo, Joseph
    Abecasis, Goncalo
    Bell, Graeme I
    Blangero, John
    Cox, Nancy J
    Duggirala, Ravindranath
    Hanis, Craig L
    Seielstad, Mark
    Wilson, James G
    Christensen, Cramer
    Brandslund, Ivan
    Rauramaa, Rainer
    Surdulescu, Gabriela L
    Doney, Alex S F
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Linneberg, Allan
    Isomaa, Bo
    Tuomi, Tiinamaija
    Jørgensen, Marit E
    Jørgensen, Torben
    Kuusisto, Johanna
    Uusitupa, Matti
    Salomaa, Veikko
    Spector, Timothy D
    Morris, Andrew D
    Palmer, Colin N A
    Collins, Francis S
    Mohlke, Karen L
    Bergman, Richard N
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Tuomilehto, Jaakko
    Hansen, Torben
    Watanabe, Richard M
    Prokopenko, Inga
    Dupuis, Josee
    Karpe, Fredrik
    Groop, Leif
    Laakso, Markku
    Pedersen, Oluf
    Florez, Jose C
    Morris, Andrew P
    Altshuler, David
    Meigs, James B
    Boehnke, Michael
    McCarthy, Mark I
    Lindgren, Cecilia M
    Gloyn, Anna L
    Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus2015Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, nr 1, artikel-id e1004876Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  • 336.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thurner, Matthias
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Robertson, Neil R.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Torres, Jason M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Rayner, N. William
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Payne, Anthony J.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Steinthorsdottir, Valgerdur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Grarup, Niels
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Schmidt, Ellen M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Sarnowski, Chloe
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Magill, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Nano, Jana
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Gieger, Christian
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Trompet, Stella
    Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Below, Jennifer E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Div Genome Res, Chungcheongbuk Do, South Korea.
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Petty, Lauren E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England.
    Bennett, Amanda J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Bork-Jensen, Jette
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Med Sch, Ann Arbor, MI 48109 USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Kardt, Kai-Uwe Ec
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany;Charite Univ Med Berlin, German Chron Kidney Dis Study, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Math & Stat, Tartu, Estonia.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Locke, Adam E.
    Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA;Washington Univ, Sch Med, Dept Med, Div Genom & Bioinformat, St Louis, MO 63110 USA.
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Ntalla, Loanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
    Nylander, Vibe
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Schoenherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Florez, Jose C.
    Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Diabet Res Ctr, Dept Med, Diabet Unit, Boston, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    France, Oscar H.
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, Leibniz Ctr Diabet Res, Dusseldorf, Germany.
    Ikram, M. Arfan
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Ligthart, Symen
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Frederiksberg, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Lyssenko, Valeriya
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Kuwait, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA;NHLBI, Framingham Heart Stud, Framingham, MA USA.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Collins, Francis S.
    NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Grallert, Harald
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Helmholtz Zentrum Munchen, Clin Cooparat Grp Type Diabet 2, Munich, Germany;Tech Univ, Helmholtz Zentrum Munchen, Clin Cooparat Grp, Nutrigen & Type Diabet 2, Munich, Germany.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Dehghan, Abbas
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Koettgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
    Rotter, Jerome, I
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Med, LABioMed, Torrance, CA 90509 USA.
    Marchini, Jonathan
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Pedersen, Oluf
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gloyn, Anna L.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Morris, Andrew P.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    McCarthy, Mark, I
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 11, s. 1505-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

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    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
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    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
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    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
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    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
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    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
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    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
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    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
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    Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany.
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    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
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    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
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    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
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    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
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    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
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    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    deCODE Genet Amgen Inc, Reykjavik, Iceland.
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    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
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    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
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    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA.
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    Penn State Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA.
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    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
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    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
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    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
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    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
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    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
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    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
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    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
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    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
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    UCL, Inst Cardiovasc Sci, London, England.
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    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany.
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    Univ Cattolica Sacro Cuore, Inst Internal & Geriatr Med, Rome, Italy.
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    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
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    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
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    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
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    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
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    Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
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    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
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    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
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    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Res Ctr Prevent & Hlth, Glostrup, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
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    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland;Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland.
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    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
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    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
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    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Minerva Fdn, Helsinki, Finland;Univ Helsinki, Dept Med, Helsinki, Finland;Univ Helsinki, Cent Hosp, Helsinki, Finland.
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    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany.
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia;Univ Tartu, Inst Math Stat, Tartu, Estonia.
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    Univ Colorado Denver, Div Bioinformat & Personalized Med, Dept Med, Aurora, CO USA.
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    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
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    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
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    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan.
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    Res Ctr Prevent & Hlth, Glostrup, Denmark;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
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    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Oulu, Inst Hlth Sci, Oulu, Finland;ASTAR, TLGM, Singapore, Singapore.
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
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    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
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    Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
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    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
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    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ntalla, Ioanna
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Dusseldorf, Leibniz Ctr Diabet Res Heinrich Heine, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
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    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
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    Univ Virginia, Sch Med, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
    Rode, Line
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Schonherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
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    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Small, Kerrin S.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
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    deCODE Genet Amgen Inc, Reykjavik, Iceland.
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    Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
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    Univ Leipzig, Dept Med, Leipzig, Germany.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
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    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
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    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
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    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
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    Univ Lille Nord France, INSERM, U1167, Inst Pasteur Lille, Lille, France.
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    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, Nuthetal, Germany.
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    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
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    NHGRI, US Natl Inst Hlth, Genome Technol Branch, Bethesda, MD 20892 USA.
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    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
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    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;German Ctr Diabet Res DZD, Neuherberg, Germany;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
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    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
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    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med EPIMED, Varese, Italy.
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    INSERM, UMR 1027, Toulouse, France;Toulouse Univ, Sch Med, Dept Cardiol, Toulouse, France.
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    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Dept Med, Boston, MA USA.
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    Ctr Noncommunicable Dis, Karachi, Pakistan.
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    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
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    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
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    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
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    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
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    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth NI, Belfast, Antrim, North Ireland.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany.
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France.
    Morris, Andrew D.
    Ninewells Hosp, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland;Med Sch, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Murray, Alison D.
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Biomed Imaging Ctr, Aberdeen, Scotland.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden.
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Ridker, Paul M.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Rivadineira, Fernando
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Rosengren, Anders H.
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan;Sch Med, Natl Def Med Ctr, Taipei, Taiwan.
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada;Genome Quebec Innovat Ctr, Montreal, PQ, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp, Div Populat Hlth Sci, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Uitterlinden, Andre G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
    Bluher, Matthias
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany;Univ Leipzig, Dept Med, Leipzig, Germany.
    Butterworth, Adam S.
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    van Duijn, Cornelia
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Dupuis, Josee
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany;Ludwig Maximillians Univ Munich, Helmholtz Zentrum Munchen, Clin Cooperat Grp Type Diabet 2, Munich, Germany;Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Helmholtz Zentrum Munchen, Munich, Germany.
    Groop, Leif
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Kooner, Jaspal Singh
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, Hammersmith Campus, London, England.
    Kottgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Kuulasmaa, Kari
    Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Yongmei
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC USA.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Marchini, Jonathan
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Pankow, James S.
    Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Univ Cambridge, Sch Clin Med, Dept Hematol, Cambridge, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Stumvoll, Michael
    Univ Hosp Leipzig, Div Endocrinol, Leipzig, Germany;Univ Hosp Leipzig, Div Nephrol, Leipzig, Germany.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Dasman, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metabol Res Labs, Cambridge, England.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Harvard Med Sch, Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA;Ctr Noncommunicable Dis, Karachi, Pakistan.
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Med,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 559-571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 x 10(-7)); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio <= 1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 338.
    Malik, Rainer
    et al.
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Chauhan, Ganesh
    Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France.
    Traylor, Matthew
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Okada, Yukinori
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Mishra, Aniket
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Rutten-Jacobs, Loes
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Giese, Anne-Katrin
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA.
    van der Laan, Sander W.
    Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept Cardiol, Utrecht, Netherlands.
    Gretarsdottir, Solveig
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Anderson, Christopher D.
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Chong, Michael
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Adams, Hieab H. H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
    Ago, Tetsuro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Amouyel, Philippe
    Univ Lille, Risk Factors & Mol Determinants Aging Related Dis, Inst Pasteur Lille, INSERM,LabEx DISTALZ,UMR1167, Lille, France;CHU Lille, Epidemiol & Publ Hlth Dept, Lille, France.
    Ay, Hakan
    MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Harvard Med Sch, MGH, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
    Benavente, Oscar R.
    Univ British Columbia, Brain Res Ctr, Div Neurol, Fac Med, Vancouver, BC, Canada.
    Bevan, Steve
    Univ Lincoln, Sch Life Sci, Lincoln, England.
    Boncoraglio, Giorgio B.
    IRCCS, Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy.
    Brown, Robert D., Jr.
    Mayo Clin, Dept Neurol, Rochester, MN USA.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood, Cambridge, England;Univ Cambridge, Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Carrera, Caty
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Carty, Cara L.
    Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA;George Washington Univ, Ctr Translat Sci, Washington, DC USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Chen, Wei-Min
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Cole, John W.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Populat Hlth Sci, Jackson, MS 39216 USA.
    Cotlarciuc, Ioana
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, Hope Ctr Program Prot Aggregat & Neurodegenerat H, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Cambridge, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
    DeStefano, Anita L.
    Boston Univ, Sch Publ Hlth, Boston, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    den Hoed, Marcel
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Duan, Qing
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Engelter, Stefan T.
    Basel Univ Hosp, Dept Neurol, Basel, Switzerland;Basel Univ Hosp, Stroke Ctr, Basel, Switzerland;Univ Basel, Neurorehabilitat Unit, Basel, Switzerland;Univ Ctr Med Aging & Rehabil Basel, Felix Platter Hosp, Basel, Switzerland.
    Falcone, Guido J.
    Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
    Grewal, Raji P.
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc Res Inst, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Haessler, Jeffrey
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Harris, Tamara B.
    NIH, Natl Inst Aging, Lab Epidemiol & Populat Sci, Bldg 10, Bethesda, MD 20892 USA.
    Hassan, Ahamad
    Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England.
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Helsinki, Finland;Inst Mol Med Finland, FIMM, Helsinki, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Holliday, Elizabeth G.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW, Australia;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.
    Howard, George
    Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
    Hsu, Fang-Chi
    Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
    Hyacinth, Hyacinth I.
    Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA.
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Epidemiol, Birmingham, AL 35294 USA.
    Jian, Xueqiu
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
    Jimenez-Conde, Jordi
    Univ Autonoma Barcelona, Inst Hosp Mar Invest Med, Neurol Dept, Neurovasc Res Grp NEUVAS, Barcelona, Spain.
    Johnson, Julie A.
    Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Kanai, Masahiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Harvard Med Sch, Program Bioinformat & Integrat Gen, Boston, MA USA.
    Keene, Keith L.
    East Carolina Univ, Dept Biol, Greenville, NC USA;East Carolina Univ, Ctr Hlth Dispar, Greenville, NC USA.
    Kissela, Brett M.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kleindorfer, Dawn O.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Kubo, Michiaki
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Lange, Leslie A.
    Univ Colorado Denver, Dept Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    NIH, Natl Inst Aging, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Jin-Moo
    Washington Univ, Sch Med, Dept Neurol Radiol & Biomed Engn, St Louis, MO USA.
    Lemmens, Robin
    Univ Leuven, KU Leuven, Dept Neurosci Expt Neurol, Leuven, Belgium;Univ Hosp Leuven, Dept Neurol, VIB Ctr Brain & Dis Res, Leuven, Belgium.
    Leys, Didier
    Univ Lille, CHU Lille, INSERM, U 1171, Lille, France.
    Lewis, Cathryn M.
    Kings Coll London, Dept Med & Mol Genet, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London, England.
    Lin, Wei-Yu
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Newcastle Univ, Northern Inst Canc Res, Newcastle, NSW, Australia.
    Lindgren, Arne G.
    Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden;Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden.
    Lorentzen, Erik
    Univ Gothenburg, Bioinformat Core Facil, Gothenburg, Sweden.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Maguire, Jane
    Univ Technol Sydney, Fac Hlth, Ultimo, NSW, Australia.
    Manichaikul, Ani
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    McArdle, Patrick F.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Meschia, James F.
    Mayo Clin, Dept Neurol, Jacksonville, FL USA.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA;Baltimore Vet Adm, Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Sch Med, Div Geriatr, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Memory Impairment & Neurodegenerat Dementia Ctr, Jackson, MS 39216 USA.
    Nalls, Michael A.
    NIH, Natl Inst Aging, Lab Neurogenet, Bldg 10, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    O'Donnell, Martin J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Pulit, Sara L.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
    Rannikmae, Kristiina
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Rexrode, Kathryn M.
    Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Rost, Natalia S.
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA.
    Rothwell, Peter M.
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sakaue, Saori
    Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan.
    Sale, Michele M.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sapkota, Bishwa R.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Schmidt, Carsten O.
    Univ Med Greifswald, SHIP KEF, Inst Community Med, Greifswald, Germany.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany.
    Sharma, Pankaj
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Slowik, Agnieszka
    Jagiellonian Univ, Dept Neurol, Krakow, Poland.
    Sudlow, Cathie L. M.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Tanislav, Christian
    Justus Liebig Univ, Dept Neurol, Giessen, Germany.
    Tatlisumak, Turgut
    Univ Gothenburg, Sahlgrenska Acad, Inst Neuroscience & Physiol, Dept Clin Neurosci Neurol, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Thijs, Vincent N. S.
    Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Heidelberg, Vic, Australia;Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia.
    Thorleifsson, Gudmar
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Tiedt, Steffen
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, Leiden, Netherlands.
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands;Ctr Med Syst Biol, Leiden, Netherlands.
    Walters, Matthew
    Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland.
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wassertheil-Smoller, Sylvia
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Boston, MA USA.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Pastinen, Tomi
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Ruusalepp, Arno
    Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia;Clin Gene Networks AB, Stockholm, Sweden.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Koplev, Simon
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bjorkegren, Johan L. M.
    Clin Gene Networks AB, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Univ Tartu, Biomeedikum, Inst Biomedicine & Translat Med, Dept Pathophysiol, Tartu, Estonia;Karolinska Univ Ssjukhuset, Dept Med, Integrated Cardio Metab Ctr, Huddinge, Sweden.
    Codoni, Veronica
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Civelek, Mete
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
    Smith, Nicholas L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA;VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
    Tregouet, David A.
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Christophersen, Ingrid E.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Roselli, Carolina
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Kato, Norihiro
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    He, Jiang
    Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Imperial Coll London, NIHR Imperial Biomed Res Ctr, London, England.
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.
    Takeuchi, Fumihiko
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Natl Heart Lung & Blood Res Inst, Div Intramural Res, Populat Sci Branch, Framingham, MA USA.
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA;Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Jern, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden.
    Strbian, Daniel
    Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland;Univ Helsinki, Clin Neurosci, Neurol, Helsinki, Finland.
    Fernandez-Cadenas, Israel
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Longstreth, W. T., Jr.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
    Rolfs, Arndt
    Univ Clin Rostock, Albrecht Kossel Inst, Rostock, Germany.
    Hata, Jun
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    Woo, Daniel
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Rosand, Jonathan
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
    Stefansson, Kari
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Worrall, Bradford B.
    Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA;Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
    Kittner, Steven J.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Seshadri, Sudha
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA.
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Markus, Hugh S.
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Kamatani, Yoichiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
    Debette, Stephanie
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 524-537Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

  • 339. Malmqvist, K
    et al.
    Ohman, K P
    Lind, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nyström, F
    Kahan, T
    Relationships between left ventricular mass and the renin-angiotensin system, catecholamines, insulin and leptin.2002Ingår i: J Intern Med, ISSN 0954-6820, Vol. 252, nr 5, s. 430-9Artikel i tidskrift (Refereegranskat)
  • 340. Malmqvist, Karin
    et al.
    Kahan, Thomas
    Edner, Magnus
    Held, Claes
    Hägg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Muller-Brunotte, Richard
    Nyström, Fredrik
    Öhman, K. Peter
    Osbakken, Mary D.
    Östergern, Jan
    Regression of left ventricular hypertrophy in human hypertension with irbesartan2001Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 19, nr 6, s. 1167-1176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

  • 341. Malmqvist, Karin
    et al.
    Ohman, K Peter
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nyström, Fredrik
    Kahan, Thomas
    Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).2003Ingår i: J Cardiovasc Pharmacol, ISSN 0160-2446, Vol. 42, nr 6, s. 719-26Artikel i tidskrift (Refereegranskat)
  • 342.
    Manning, Alisa
    et al.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Highland, Heather M.
    Univ Texas MD Anderson Canc Ctr, Human Genet Ctr, Houston, TX 77030 USA.;Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.;Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Gasser, Jessica
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Sim, Xueling
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Tukiainen, Taru
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;23andMe, Mountain View, CA USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Rivas, Manuel A.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Locke, Adam E.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Pers, Tune H.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Boston Childrens Hosp, Div Endocrinol & Genet, Boston, MA USA.;Boston Childrens Hosp, Div Genom, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes, Boston, MA USA.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Vinuela, Ana
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Univ Geneva, Sch Med, Dept Genet Med & Dev, Geneva, Switzerland.;Univ Geneva, Inst Genet & Genom Geneva, Geneva, Switzerland..
    Brown, Andrew A.
    Wellcome Trust Sanger Inst, Hinxton, England.;Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res, Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, Oslo, Norway..
    Wu, Ying
    Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Fuchsberger, Christian
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.;Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands..
    Gaulton, Kyle J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Teslovich, Tanya M.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Chen, Yuhui
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Kang, Hyun Min
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kumar, Ashish
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol Unit, Basel, Switzerland..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Ma, Clement
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Moutsianas, Loukas
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Scott, Laura J.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Univ Helsinki, Unit Gen Practice, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Vaasa Cent Hosp, Vaasa, Finland.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Tampere, Dept Clin Chem, Fimlab Labs, Sch Med, Tampere, Finland..
    Jula, Antti
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Koskinen, Seppo
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Lehtimaki, Terho
    Palotie, Aarno
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Jacobs, Suzanne B. R.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Wessel, Jennifer
    Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN USA.;Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA..
    Chu, Audrey Y.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.;Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Chines, Peter S.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Huyghe, Jeroen R.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jackson, Anne U.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jun, Goo
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Stringham, Heather M.
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Farjoun, Yossi
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Goldstein, Jacqueline I.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    de Angelis, Martin Hrabe
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Tech Univ Munich, Sch Life Sci Weihenstephan, Inst Expt Genet, Freising Weihenstephan, Germany..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA..
    Schwarzmayr, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Strom, Tim M.
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Neuherberg, Germany..
    Wieland, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland..
    Brandslund, Ivan
    Univ Southern Denmark, Dept Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Lakka, Timo A.
    Univ Eastern FinIand, Inst Biomed, Dept Physiol, Kuopio, Finland.;Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Nilsson, Peter
    Lund Univ, Fac Med, Dept Clin Sci, Malmo, Sweden..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England..
    Varga, Tibor V.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Franks, Paul W.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Kumar, Satish
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res & Dev Serv, San Antonio, TX USA..
    Curran, Joanne E.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Dept Internal Med, Sect Nephrol, Winston Salem, NC USA..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Narisu, Narisu
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Bonnycastle, Lori L.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Swift, Amy
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Pasko, Dorota
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    Wood, Andrew R.
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Pollin, Toni I.
    Univ Maryland, Dept Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA.;Univ Haifa, Fac Nat Sci, Haifa, Israel..
    Glaser, Benjamin
    Hadassah Hebrew Univ, Endocrinol & Metab Serv, Med Ctr, Jerusalem, Israel..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany..
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany..
    Roden, Michael
    Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;Partner Dusseldorf, German Ctr Diabet Res, Dusseldorf, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Illig, Thomas
    German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, Germany..
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Gieger, Christian
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Lannfelt, L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Oksa, Heikki
    Pirkanmaa Hosp Dist, Tampere, Finland..
    Scott, William R.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Afzal, Uzma
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Tan, Sian-Tsung
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, Translat Lab Genet Med, Singapore, Singapore..
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Sehmi, Jobanpreet
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Kooner, Jaspal Singh
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Lee, Jong-Young
    Minist Hlth & Welf, Seoul, South Korea..
    Han, Bok-Ghee
    Korea Natl Res Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Karajamaki, Annemari
    Vaasa Hlth Care Ctr, Vaasa, Finland.;Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Hypertens & Cardiovasc Dis, Malmo, Sweden..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Diabet & Cardiovasc Dis Genet Epidemiol, Malmo, Sweden..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Aguilar, David
    Baylor Coll Med, Cardiovasc Div, Houston, TX 77030 USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Khor, Chiea-Chuen
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore..
    Chia, Kee Seng
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Lim, Wei Yen
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Cheng, Ching-Yu
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Ctr Quantitat Med, Off Clin Sci, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Cardiovasc Metab Disorders Program, Singapore, Singapore..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Linneberg, Allan
    Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Meitinger, Thomas
    German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Neuherberg, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Cent Hosp, Dept Endocrinol, Helsinki, Finland..
    Hakaste, Liisa
    Folkhalsan Res Ctr, Helsinki, Finland..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Lauritzen, Torsten
    Aarhus Univ, Dept Publ Hlth, Sect Gen Practice, Aarhus, Denmark..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Farmer, Andrew J.
    Univ Oxford, Dept Primary Care Hlth Sci, Oxford, England..
    Frayling, Timothy M.
    Univ Exeter, Genet Complex Traits, Med Sch, Exeter, Devon, England..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Med Res Labs, Cambridge, England..
    Walker, Mark
    Univ Newcastle, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland..
    Stancakova, Alena
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Inst Metab Sci, Med Res Labs, Cambridge, England..
    Bharadwaj, Dwaipayan
    CSIR Inst Genom & Integrat Biol, Funct Genom Unit, New Delhi, India..
    Chan, Juliana
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Chandak, Giriraj R.
    CSIR Ctr Cellular Mol Biol, Hyderabad, Andhra Pradesh, India..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Donnelly, Peter J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India. Imperial Coll London, MRC, PHE Ctr Environm & Hlth, London, England..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Froguel, Philippe
    CNRS, Inst Biol Lille, Genom & Mol Physiol, Lille, France..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Ma, Ronald C. W.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    McVean, Gilean
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Park, Taesung
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea.;Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India. Imperial Coll London, MRC, PHE Ctr Environm & Hlth, London, England..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
    Scott, James
    Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Teo, Yik Ying
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA USA..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Inst Med Res, Helsinki, Finland..
    Kesaniemi, Y. Antero
    Univ Oulu, Inst Clin Med, Fac Med, Oulu, Finland..
    Uusitupa, Matti
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Rauramaa, Rainer
    Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland..
    Prokopenko, Inga
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Div Mol Med, Dundee, Scotland..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA..
    Collins, Francis S.
    NHGRI, NIH, Bethesda, MD 20892 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden.;Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Dasman Diabet Inst, Dasman, Kuwait..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, Diabet & Endocrinol Unit, Malmo, Sweden..
    Jorgensen, Torben
    Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Kuusisto, Johanna
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Abecasis, GonOalo
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bell, Graeme I.
    Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Blangero, John
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Cox, Nancy J.
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, Inst Human Genet, San Francisco, CA 94143 USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Helsinki, Finland..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA..
    Mohlke, Karen L.
    Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA..
    Meigs, James B.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA..
    Laakso, Markku
    Univ Eastern Finland, Fac Hlth Sci, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Boehnke, Michael
    Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Altshuler, David
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA..
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England..
    A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk2017Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, nr 7, s. 2019-2032Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.

  • 343. Manning, Alisa K.
    et al.
    Hivert, Marie-France
    Scott, Robert A.
    Grimsby, Jonna L.
    Bouatia-Naji, Nabila
    Chen, Han
    Rybin, Denis
    Liu, Ching-Ti
    Bielak, Lawrence F.
    Prokopenko, Inga
    Amin, Najaf
    Barnes, Daniel
    Cadby, Gemma
    Hottenga, Jouke-Jan
    Ingelsson, Erik
    Jackson, Anne U.
    Johnson, Toby
    Kanoni, Stavroula
    Ladenvall, Claes
    Lagou, Vasiliki
    Lahti, Jari
    Lecoeur, Cecile
    Liu, Yongmei
    Martinez-Larrad, Maria Teresa
    Montasser, May E.
    Navarro, Pau
    Perry, John R. B.
    Rasmussen-Torvik, Laura J.
    Salo, Perttu
    Sattar, Naveed
    Shungin, Dmitry
    Strawbridge, Rona J.
    Tanaka, Toshiko
    van Duijn, Cornelia M.
    An, Ping
    de Andrade, Mariza
    Andrews, Jeanette S.
    Aspelund, Thor
    Atalay, Mustafa
    Aulchenko, Yurii
    Balkau, Beverley
    Bandinelli, Stefania
    Beckmann, Jacques S.
    Beilby, John P.
    Bellis, Claire
    Bergman, Richard N.
    Blangero, John
    Boban, Mladen
    Boehnke, Michael
    Boerwinkle, Eric
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Boettcher, Yvonne
    Bouchard, Claude
    Brunner, Eric
    Budimir, Danijela
    Campbell, Harry
    Carlson, Olga
    Chines, Peter S.
    Clarke, Robert
    Collins, Francis S.
    Corbaton-Anchuelo, Arturo
    Couper, David
    de Faire, Ulf
    Dedoussis, George V.
    Deloukas, Panos
    Dimitriou, Maria
    Egan, Josephine M.
    Eiriksdottir, Gudny
    Erdos, Michael R.
    Eriksson, Johan G.
    Eury, Elodie
    Ferrucci, Luigi
    Ford, Ian
    Forouhi, Nita G.
    Fox, Caroline S.
    Franzosi, Maria Grazia
    Franks, Paul W.
    Frayling, Timothy M.
    Froguel, Philippe
    Galan, Pilar
    de Geus, Eco
    Gigante, Bruna
    Glazer, Nicole L.
    Goel, Anuj
    Groop, Leif
    Gudnason, Vilmundur
    Hallmans, Goeran
    Hamsten, Anders
    Hansson, Ola
    Harris, Tamara B.
    Hayward, Caroline
    Heath, Simon
    Hercberg, Serge
    Hicks, Andrew A.
    Hingorani, Aroon
    Hofman, Albert
    Hui, Jennie
    Hung, Joseph
    Jarvelin, Marjo-Riitta
    Jhun, Min A.
    Johnson, Paul C. D.
    Jukema, J. Wouter
    Jula, Antti
    Kao, W. H.
    Kaprio, Jaakko
    Kardia, Sharon L. R.
    Keinanen-Kiukaanniemi, Sirkka
    Kivimaki, Mika
    Kolcic, Ivana
    Kovacs, Peter
    Kumari, Meena
    Kuusisto, Johanna
    Kyvik, Kirsten Ohm
    Laakso, Markku
    Lakka, Timo
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lathrop, G. Mark
    Launer, Lenore J.
    Leander, Karin
    Li, Guo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindstrom, Jaana
    Lobbens, Stephane
    Loos, Ruth J. F.
    Luan, Jian'an
    Lyssenko, Valeriya
    Magi, Reedik
    Magnusson, Patrik K. E.
    Marmot, Michael
    Meneton, Pierre
    Mohlke, Karen L.
    Mooser, Vincent
    Morken, Mario A.
    Miljkovic, Iva
    Narisu, Narisu
    O'Connell, Jeff
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Lyle J.
    Palotie, Aarno
    Pankow, James S.
    Peden, John F.
    Pedersen, Nancy L.
    Pehlic, Marina
    Peltonen, Leena
    Penninx, Brenda
    Pericic, Marijana
    Perola, Markus
    Perusse, Louis
    Peyser, Patricia A.
    Polasek, Ozren
    Pramstaller, Peter P.
    Province, Michael A.
    Raikkonen, Katri
    Rauramaa, Rainer
    Rehnberg, Emil
    Rice, Ken
    Rotter, Jerome I.
    Rudan, Igor
    Ruokonen, Aimo
    Saaristo, Timo
    Sabater-Lleal, Maria
    Salomaa, Veikko
    Savage, David B.
    Saxena, Richa
    Schwarz, Peter
    Seedorf, Udo
    Sennblad, Bengt
    Serrano-Rios, Manuel
    Shuldiner, Alan R.
    Sijbrands, Eric J. G.
    Siscovick, David S.
    Smit, Johannes H.
    Small, Kerrin S.
    Smith, Nicholas L.
    Smith, Albert Vernon
    Stancakova, Alena
    Stirrups, Kathleen
    Stumvoll, Michael
    Sun, Yan V.
    Swift, Amy J.
    Toenjes, Anke
    Tuomilehto, Jaakko
    Trompet, Stella
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Vikstrom, Max
    Vitart, Veronique
    Vohl, Marie-Claude
    Voight, Benjamin F.
    Vollenweider, Peter
    Waeber, Gerard
    Waterworth, Dawn M.
    Watkins, Hugh
    Wheeler, Eleanor
    Widen, Elisabeth
    Wild, Sarah H.
    Willems, Sara M.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wright, Alan F.
    Yaghootkar, Hanieh
    Zelenika, Diana
    Zemunik, Tatijana
    Zgaga, Lina
    Wareham, Nicholas J.
    McCarthy, Mark I.
    Barroso, Ines
    Watanabe, Richard M.
    Florez, Jose C.
    Dupuis, Josee
    Meigs, James B.
    Langenberg, Claudia
    A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance2012Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 6, s. 659-669Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

  • 344.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal.
    Dudding, Tom
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Haworth, Simon
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam.
    Voortman, Trudy
    Erasmus MC, Dept Epidemiol, Rotterdam.
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, Rotterdam.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Robinson-Cohen, Cassiane
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Cousminer, Diana
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Nethander, Maria
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Vanderput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Noordam, Raymond
    Leiden Univ, Sect Gerontol & Geriatr, Dept Internal Med, Med Ctr, Leiden.
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Greenwood, Celia
    McGill Univ, Dept Human Genet, Montreal, PQ.
    Biggs, Mary Lou
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle.
    Psaty, Bruce
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle.
    Rotter, Jerome
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance.
    Zemel, Babette
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Mitchell, Jonathan
    Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia.
    Taylor, Bruce
    Univ Tasmania, Menzies Res Inst Tasmania, Hobart.
    Lorentzon, Matthias
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med, Sahlgrenska Acad, Gothenburg.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmö.
    Jaddoe, Vincent
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Tiemeier, Henning
    Erasmus MC, Generat Study Grp R, Rotterdam.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam.
    Franco, Oscar
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Uitterlinden, Andre
    Erasmus MC, Dept Internal Med, Rotterdam.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam.
    van Schoor, Natasja
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam.
    Ham, Annelies
    Erasmus MC, Dept Internal Med, Rotterdam.
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam.
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston.
    de Mutsert, Renee
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Rosendaal, Fritz
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    den Heijer, Martin
    Vrije Univ Amsterdam, Dept Endocrinol, Med Ctr, Amsterdam.
    Wang, Thomas
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle.
    Ohlsson, Claes
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, Gothenburg.
    de Groot, Lisette
    Wageningen Univ, Dept Human Nutr, Wageningen.
    Grant, Struan
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia.
    Kiel, Douglas
    Hebrew SeniorLife, Inst Aging Res, Boston.
    Zillikens, Carola
    Erasmus MC, Dept Internal Med, Rotterdam.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam.
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge.
    Timpson, Nicholas
    Univ Bristol, IEU, MRC, Bristol, Avon.
    Richards, Brent
    McGill Univ, Dept Human Genet, Montreal.
    Low Frequency Coding Variation in CYP2R1 has Large Effects on Vitamin D Level and Risk of Multiple Sclerosis2017Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr S1, s. S319-S320, artikel-id Meeting Abstract: MO0459Artikel i tidskrift (Övrigt vetenskapligt)
  • 345.
    Manousaki, Despoina
    et al.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Dudding, Tom
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Haworth, Simon
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Voortman, Trudy
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands..
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Robinson-Cohen, Cassianne
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Cousminer, Diana L.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, S-41390 Gothenburg, Sweden..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, NL-2333 ZA Leiden, Netherlands..
    Forgetta, Vincenzo
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada..
    Greenwood, Celia M. T.
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Oncol, Montreal, PQ H4A 3T2, Canada..
    Biggs, Mary L.
    Univ Washington, Dept Med & Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Kaiser Permanente Washington Hlth Res Unit, Seattle, WA 98101 USA..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Zemel, Babette S.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Mitchell, Jonathan A.
    Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA..
    Taylor, Bruce
    Univ Tasmania, Menzies Inst Med Res, Locked Bag 23, Hobart, Tas 7000, Australia..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden.;Sahlgrens Univ Hosp, Geriatr Med, S-43180 Molndal, Sweden..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, S-22241 Malmo, Sweden.;Skane Univ Hosp, Dept Orthopaed, S-22241 Malmo, Sweden..
    Jaddoe, Vincent V. W.
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Tiemeier, Henning
    Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Child & Adolescent Psychiat Psychol, NL-3015 GE Rotterdam, Netherlands..
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Utterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Broer, Linda
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands..
    Ham, Annelies C.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, NL-3015 GE Rotterdam, Netherlands..
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands..
    den Heijer, Martin
    Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, NL-1081 HV Amsterdam, Netherlands..
    Wang, Thomas J.
    Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kestenbaum, Bryan
    Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden..
    Mellström, Dan K
    Univ Gothenburg, Sahlgrenska Acad, Inst Med,Ctr Bone & Arthrit, Dept Internal Med & Clin Nutr, S-40530 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, S-43180 Molndal, Sweden..
    de Groot, Lisette C. P. G. M.
    Wageningen Univ, Div Human Nutr, NL-6708 WE Wageningen, Netherlands..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Kiel, Douglas P.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02142 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Generat R Study Grp, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Sawcer, Stephen
    Univ Cambridge, Dept Clin Neurosci, Box 165,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England..
    Timpson, Nicholas J.
    Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Richards, J. Brent
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.;McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada..
    Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis2017Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 101, nr 2, s. 227-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

  • 346.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Lindgren, Cecilia M.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England;Univ Oxford, Big Data Inst, Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7LF, England.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity2018Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, nr 11, artikel-id 1791Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of delta-5-desaturase (D5D), delta-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 x 10(-70)) and adipose tissue (p = 1.1 x 10(-27)). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 x 10(-67); PDXDCI, p = 4.8 x 10(-8); and near MC4R, p = 3.7 x 10(-8)) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 x 10(-19)). Genetic variants near MC4R were associated with IS (p = 3.8 x 10(-3)). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.

  • 347.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Pingel, Ronnie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Rosqvist, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lindroos, Anna Karin
    Natl Food Agency, Uppsala, Sweden;Univ Gothenburg, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Eriksson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Oscarsson, Jan
    AstraZeneca Gothenburg, Molndal, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Interrelationships Between Fatty Acid Composition in Plasma Cholesterol Esters and Phospholipids in Men and Women: A Pooled Analysis2017Ingår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 71, s. 372-372Artikel i tidskrift (Övrigt vetenskapligt)
  • 348.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Pingel, Ronnie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Rosqvist, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lindroos, Anna Karin
    Natl Food Agcy, Uppsala, Sweden.;Univ Gothenburg, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. en..
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Oscarsson, Jan
    AstraZeneca R&D, Gothenburg, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations2017Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 147, nr 11, s. 2118-2125Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatty acid (FA) proportions in cholesterol esters (CEs) and plasma phospholipids are widely used as dietary biomarkers. Information on how proportions in these fractions correlate could have implications for interpretation and use of FA biomarkers in observational and interventional studies. Objective: We investigated correlations between FA proportions in CEs and phospholipids in free-living individuals and assessed how diet-induced alterations of FA proportions correlate between fractions. Methods: Spearman's rank correlation coefficients (rs) between FA proportions (percentage of total FAs) in circulating CEs and phospholipids were calculated separately in 8 individual study populations including Swedish females and males (N = 2052; age range: 11-84 y), and pooled by inverse-variance weighted meta-analysis. In addition, study populations were stratified by age, sex, body mass index (BMI; in kg/m(2)), and diabetes status, and strata-specific rs were pooled by meta-analysis. In 2 randomized trials (N = 79) in which dietary saturated FAs were isocalorically replaced with unsaturated FAs, treatment-wise calculations of rs were conducted between FA changes in CEs and phospholipids. Results: Overall, FA proportions in CEs and phospholipids correlated well and especially strongly for polyunsaturated FAs (PUFAs), with pooled rs (95% CIs) ranging from 0.74 (0.72, 0.76) for a-linolenic acid to 0.92 (0.91, 0.93) for eicosapentaenoic acid. Weak correlations (pooled rs <0.4) were observed only for palmitic acid and stearic acid, with pooled rs (95% CIs): 0.29 (0.24, 0.33) and 0.30 (0.25, 0.34), respectively. Overall, correlations were not affected by age, sex, BMI, or diabetes status. Strong correlations (r(s) >= 0.6) between diet-induced FA changes in CEs and phospholipids were observed for most PUFAs. Conclusions: Proportions of most FAs in CEs and phospholipids ranked individuals similarly, suggesting that FA proportions in these fractions can be used interchangeably in populations of diverse age, sex, body composition, and diabetes status. Caution is advised, however, when comparing results from studies assessing palmitic acid or stearic acid in different lipid fractions.

  • 349.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Wu, Jason H. Y.
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Imamura, Fumiaki
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Del Gobbo, Liana C.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Fretts, Amanda
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    de Goede, Janette
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Shi, Peilin
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Tintle, Nathan
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Wennberg, Maria
    Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Chen, Tzu-An
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Otto, Marcia C. de Oliveira
    Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Hirakawa, Yoichiro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Fukuoka, Japan.
    Eriksen, Helle Hojmark
    Aalborg Univ Hosp, Unit Epidemiol & Biostat, Aalborg, Denmark.
    Kroeger, Janine
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Laguzzi, Federica
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lankinen, Maria
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Murphy, Rachel A.
    Univ British Columbia, Vancouver, BC, Canada.
    Prem, Kiesha
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Samieri, Cecilia
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Virtanen, Jyrki
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Wood, Alexis C.
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Wong, Kerry
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Yang, Wei-Sin
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan.
    Zhou, Xia
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Baylin, Ana
    Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, Ann Arbor, MI 48109 USA;Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Boer, Jolanda M. A.
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands.
    Brouwer, Ingeborg A.
    Vrije Univ, Hlth Sci, Amsterdam, Netherlands.
    Campos, Hannia
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Chaves, Paulo H. M.
    Florida Int Univ, Herbert Wertheim Coll Med, Benjamin Leon Geriatr Res & Educ, Miami, FL 33199 USA.
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan;Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    de Faire, Ulf
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Djousse, Luc
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland.
    El-Abbadi, Naglaa
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Forouhi, Nita G.
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Gaziano, J. Michael
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Gigante, Bruna
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Giles, Graham
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Guallar, Eliseo
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Div Environm Epidemiol, Baltimore, MD USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.
    Harris, Tamara
    NIA, Bethesda, MD 20892 USA.
    Harris, William S.
    Univ South Dakota, Dept Internal Med, Sanford Sch Med, Sioux Falls, SD USA;OmegaQuant Analyt LLC, Sioux Falls, SD USA.
    Helmer, Catherine
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Hellenius, Mai-Lis
    Karolinska Univ Hosp, Karolinska Inst, Cardiol Unit, Dept Med, Stockholm, Sweden.
    Hodge, Allison
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Jacques, Paul F.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit Skelleftea, Umea, Sweden.
    Kalsbeek, Anya
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Koh, Woon-Puay
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.
    Leander, Karin
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Luben, Robert
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Luo, Juhua
    Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA.
    Mursu, Jaakko
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Fukuoka, Japan.
    Overvad, Kim
    Aarhus Univ, Dept Publ Hlth, Sect Epidemiol, Aarhus, Denmark;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Study, Seattle, WA USA;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rimm, Eric
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Siscovick, David
    New York Acad Med, New York, NY USA.
    Nielsen, Michael Skjelbo
    Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Smith, Albert, V
    Iceland Heart Assoc, Kopavogur, Iceland.
    Steffen, Brian T.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Steffen, Lyn
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Tunstall-Pedoe, Hugh
    Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland.
    Uusitupa, Matti I. J.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Veenstra, Jenna
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Wareham, Nick
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Willett, Walter
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Woodward, Mark
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia;Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland;Univ Oxford, George Inst Global Hlth, Oxford, England.
    Yuan, Jian-Min
    Univ Pittsburgh, Div Canc Control & Populat Sci, UPMC Hillman Canc, Pittsburgh, PA 15260 USA;Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies2019Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 21, s. 2422-2436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

    Methods:

    We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

    Results:

    In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

    Conclusions:

    In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

  • 350.
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    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
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    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Kjaer, Troels R.
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Fine, Rebecca S.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
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    Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
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    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
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    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
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    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
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    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England..
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    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
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    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany..
    Esko, Tonu
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63108 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA..
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    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA..
    Rivas, Manuel A.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England..
    Vedantam, Sailaja
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
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    Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
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    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA..
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    Ctr Control Chron Dis, Dhaka 1212, Bangladesh..
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    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
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    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
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    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
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    INSERM, U1167, F-59019 Lille, France.;Inst Pasteur, U1167, F-59019 Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, F-59019 Lille, France..
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    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
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    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark..
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    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
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    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, D-14558 Nuthetal, Germany..
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    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
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    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
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    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
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    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
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    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England..
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    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
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    Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
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    Univ Washington, Dept Med, Seattle, WA 98195 USA..
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    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA..
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    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
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    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
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    Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark..
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    Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
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    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
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    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
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    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
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    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
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    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands..
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    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
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    Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
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    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.;Univ Cambridge, Dept Med, Cambridge Escellence, British Heart Fdn, Cambridge CB2 0QQ, England..
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    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
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    Univ Med Ctr Utrecht, Dept Vasc Surg, Div Surg Specialties, NL-3584 CX Utrecht, Netherlands..
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    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
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    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
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    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
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    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
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    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
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    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
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    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
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    Univ Cambridge, Dept Publ Hlth & Pri