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  • 151.
    Hedman, Åsa K.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Zilmer, Mihkel
    Univ Tartu, Inst Biomed & Translat Med, Dept Biochem, Ctr Excellence Genom & Translat Med, Tartu, Estonia..
    Sundström, Johan
    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.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    DNA methylation patterns associated with oxidative stress in an ageing population2016Inngår i: BMC Medical Genomics, ISSN 1755-8794, E-ISSN 1755-8794, Vol. 9, artikkel-id 72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease. Methods: To investigate the role of epigenetic variation in oxidative stress marker levels and subsequent development of CVD and T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH], oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low-density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC]) and incident disease in up to 966 age-matched individuals. Results: In total, we found 66 cytosine-guanine (CpG) sites associated with one or more oxidative stress markers (false discovery rate [FDR] <0.05). These sites were enriched in regulatory regions of the genome. Genes annotated to CpG sites showed enrichment in annotation clusters relating to phospho-metabolism and proteins with pleckstrin domains. We investigated the contribution of oxidative stress-associated CpGs to development of cardiometabolic disease. Methylation variation at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events during 10 years of follow-up (all permutation p-values < 0.01), indicating a role of epigenetic regulation in oxidative stress processes leading to development or progression of diabetes. Methylation QTL (meQTL) analysis showed significant associations with genetic sequence variants in cis at 28 (42%) of oxidative stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with genotype-phenotype associations indicated that genetic effects on oxidative stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA methylation. Conclusions: In conclusion, we report novel associations of DNA methylation with oxidative stress, some of which also show evidence of a relation with T2D incidence.

  • 152.
    Helmersson, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Reference values for 34 frequently used laboratory tests in 80-year-old men and women2016Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 92, s. 97-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals.

    METHODS: We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.

    RESULTS: Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP).

    CONCLUSIONS: Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP.

  • 153.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, nr 2, s. 408-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE

    Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    METHODS

    This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    RESULTS

    U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.

    CONCLUSION

    This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.

  • 154.
    Henriksson, Peter
    et al.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Qing, Lu
    Karolinska Univ Hosp, Div Clin Chem, Stockholm, Sweden.
    Freyschuss, Anna
    Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
    Microvascular capillary assessment in relation to forearm blood flow2019Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, nr 5, s. 322-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. Methods Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. Results This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0 center dot 57; P<0 center dot 05). Conclusions Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.

  • 155. Ho, J. E.
    et al.
    Mahajan, A.
    Chen, M. -H
    Larson, M. G.
    McCabe, E. L.
    Ghorbani, A.
    Cheng, S.
    Johnson, A. D.
    Lindgren, C. M.
    Kempf, T.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ingelsson, E.
    Vasan, R. S.
    Januzzi, J.
    Wollert, K. C.
    Morris, A. P.
    Wang, T. J.
    Clinical and genetic correlates of growth differentiation factor 15 in the community2012Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 58, nr 11, s. 1582-1591Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Growth differentiation factor 15(GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h 2 = 0.38; P = 2.5 X 10 -11). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10 -32 for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.

  • 156.
    Hober, Andreas
    et al.
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Edfors, Fredrik
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Ryaboshapkina, Maria
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Malmqvist, Jonas
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Rosengren, Louise
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Percy, Andrew J.
    Cambridge Isotope Labs Inc, Dept Applicat Dev, Tewksbury, MA 01876 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Forsström, Björn
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden;KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden.
    Oscarsson, Jan
    AstraZeneca, Global Med Dev Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Miliotis, Tasso
    AstraZeneca, IMED Biotech Unit, Translat Sci Cardiovasc Renal & Metab, Gothenburg, Sweden.
    Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay2019Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, nr 12, s. 2433-2446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Stable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released on trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently used to investigate the effects of omega-3 carboxylic acids (OM3-CA) and fenofibrate on these 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECT I (NCT02354976). No significant changes were observed in the OM3-CA arm, whereas treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies. Applications of LC-SRM in clinical research are still limited. SIS PrEST are a novel class of standards added prior to trypsinization. We have developed a semi-automated sample preparation workflow and a SIS PrEST LC-SRM/MS Tier 2 assay for absolute quantification of 13 apolipoproteins in human plasma and applied it on clinical samples from the EFFECT I study. We demonstrate, for the first time, that SIS PrEST can be applied for exploratory biomarker research in clinical settings and capture drug effects.

  • 157.
    Hogenkamp, Pleunie S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kilander, Lena
    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.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Late-life alcohol consumption and cognitive function in elderly men2014Inngår i: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 36, nr 1, s. 243-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Moderate alcohol consumption (one to two drinks per day) has been associated with better cognitive function and lower risk of developing dementia in the elderly. In light of alcohol's well-known neurotoxic properties, more evidence from well-controlled population-based studies is required. The objective of this study was to examine whether self-reported alcohol intake at age 70 is linked to cognitive function (assessed by trail making tests (TMTs) A and B, which are measures of attention, mental speed, and flexibility) in a population-based cohort consisting of 652 cognitively healthy elderly men. Linear regression models were used to assess both cross-sectional (i.e., age 70) and prospective (i.e., age 77) associations between alcohol intake and cognitive function. The analyses were adjusted for education, body mass index, energy intake, self-reported physical activity, smoking, a history of hypertension or diabetes, apolipoprotein E epsilon 4 status, and cholesterol levels at the age of 70. Baseline data were obtained from 1990 to 1996. Self-reported alcohol intake (mean 6.9 +/- 7.1 g/day) was associated with better performance on TMT-B at ages 70 and 77 (beta = -0.87, p < 0.001). In contrast, alcohol intake was not predictive of the difference in performance on these tests between ages 70 and 77. Despite cross-sectional associations with performance in a test of executive functioning, moderate intake of alcohol was not linked to differences in cognitive performance between ages 70 and 77 in the present study. Thus, our findings do not support the view that daily moderate alcohol consumption is a recommendable strategy to slow cognitive aging in elderly populations.

  • 158.
    Holdstock, Camilla
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eden Engström, Britt
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Öhrvall, M
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundbom, M
    Karlsson, Anders F
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Effect of bariatric surgery on adipose tissue regulatory peptides and growth hormone secretion.2004Inngår i: Asia Pac J Clin Nutr, ISSN 0964-7058, Vol. 13, nr Suppl, s. S41-Artikkel i tidsskrift (Fagfellevurdert)
  • 159.
    Holdstock, Camilla
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Engström, Britt E
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ohrvall, Margareta
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundbom, Magnus
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, F Anders
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans.2003Inngår i: J Clin Endocrinol Metab, ISSN 0021-972X, Vol. 88, nr 7, s. 3177-83Artikkel i tidsskrift (Fagfellevurdert)
  • 160.
    Holdstock, Camilla
    et al.
    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.
    Eden Engström, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Karlsson, Anders
    CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects2005Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 29, nr 10, s. 1275-1280Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk ofcardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent theinsulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypasssurgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies onthe regulation of inflammatory markers.DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.

    SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.

    MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well asmarkers of glucose and lipid metabolism.

    RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRPcorrelated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, whencorrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the changein body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4(insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended toparallel the changes in CRP, but were less informative.

    CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers andimproves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistantpatients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather thanenergy supply.

  • 161. Holmlund, A.
    et al.
    Hulthe, J.
    Millgård, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sarabi, Mahziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals2002Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 165, nr 2, s. 271-276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.

  • 162.
    Holmlund, Anders
    et al.
    Uppsala Univ Reg Gavleborg, Cty Hosp Gavle, Dept Periodontol, Ctr Res & Dev, Gavle, Sweden..
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Oral health and cardiovascular disease risk in a cohort of periodontitis patients2017Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 262, s. 101-106Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: The aim of this study was to determine whether oral health is uniformly associated with three different cardiovascular diseases (CVDs), including myocardial infarction (MI), stroke, and heart failure (HF), which has not been studied previously. Methods: A full mouth investigation was performed in 8999 individuals referred to a specialized periodontology clinic between 1979 and 2012. The number of deepened pockets (NDP), number of teeth (NT), and bleeding on probing (BOP) were investigated. Incident CVD diagnosis was obtained from the Swedish cause of death and the hospital discharge registers. Results: During a median follow-up time of 15.8 years (153,103 person years at risk), 1338 incident cases of fatal/non-fatal CVD occurred (672 fatal/non-fatal MI, 545 stroke and 302 HF). When NT, BOP and NDP were all included in the same model with age, sex, smoking, calendar time, and education level, NT and NDP, but not BOP, were significantly related to future CVD (combined end-point, p=0.0003 for NT and p =0.007 for NDP). In similar analyses of 3 separate CVD outcomes, NT was significantly related to MI, with an incidence rate ratio (IRR) for a given interquartile range change of 0.90 (95% CI 0.82=0.99) and to HF, with an IRR of 0.87 (95% CI 0.77-0.99). However, NT was not significantly related to stroke. BOP and NDP were not significantly related to any of the three separate CVD outcomes. Conclusion: Oral health, mainly represented by NT, was related to incident MI and HF, but not to incident stroke. Therefore, oral health does not seem to relate to all major CV disorders in a similar fashion.

  • 163.
    Holmlund, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Cty Hosp Gavle, Dept Periodontol, S-80187 Gavle, Sweden.
    Lampa, Erik
    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.
    Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease2017Inngår i: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 96, nr 7, s. 768-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having > 10% sites with probing pocket depth > 4 mm deep and bleeding on probing at >= 20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD (n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth > 4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  • 164.
    Holmlund, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Number of teeth is related to atherosclerotic plaque in the carotid arteries in an elderly population2012Inngår i: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 83, nr 3, s. 287-291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Periodontal disease has been associated with cardiovascular disorders with an atherosclerotic background, and number of teeth (NT) has been suggested as a possible risk indicator for cardiovascular disease. The objective of this study is to investigate whether NT was related to the intima-media thickness (IMT) and to atherosclerotic plaque in carotid arteries in an elderly population.

    METHODS:

    In a population-based study including 1,016 participants aged 70 years, the NT was self-reported by 947 of the participants. Carotid artery IMT was evaluated by ultrasound. The occurrence of plaque was also measured. Logistic regression was used to analyze the associations between NT and the number of carotid arteries with plaque.

    RESULTS:

    A significant inverse relationship was found between the NT and the number of carotid arteries with plaque after adjustment for age, sex, smoking, body mass index, waist/hip ratio, blood glucose, triglycerides, cholesterol, C-reactive protein, leukocyte count, blood pressure, and Framingham risk score, with odds ratio of 0.89, 95% confidence interval of 0.82 to 0.98, and P = 0.016. The relationship was fairly linear, suggesting a dose-response relationship. When NT was divided into quintiles using the first one as referent, the relationship persisted for all quintiles except for the second one. However, no relationship to IMT was seen.

    CONCLUSION:

    The present study further emphasizes that tooth loss could be an easily obtained risk indicator for atherosclerosis.

  • 165. Hong, N-S
    et al.
    Kim, K-S
    Lee, I-K
    Lind, Monica
    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.
    Jacobs, D R
    Lee, D-H
    The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox2011Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, nr 9, s. 1170-1175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Numerous studies have documented an obesity paradox in which the overweight and obese elderly have a better prognosis than those with ideal body weight. Good prognosis among the overweight or obese elderly may reflect the relative safety of storing the harmful lipophilic chemicals, known as persistent organic pollutants (POPs), in adipose tissue rather than in other critical organs. Therefore, we hypothesized lower mortality among the obese elderly with a higher body burden of POPs, but this pattern may not exist among the obese elderly with a lower body burden of POPs.

    PARTICIPANTS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2004 study with a mean 4.2-year follow-up, we tested whether the association between fat mass and total mortality in 635 (652 for organochlorine pesticides) elderly participants aged >= 70 years differed depending on serum concentrations of 23 POPs.

    RESULTS: There were statistically significant interactions between fat mass and POPs in predicting total mortality. In those with low POP concentrations, there was no obesity paradox; mortality increased with fat mass (hazard ratios about 2-3 in the highest vs lowest quintile of fat mass). However, consistent with an obesity paradox, these patterns completely disappeared in those with high POP concentrations. Compared with the lowest quintile of fat mass, statistically significantly lower mortality was observed in the elderly in the third to fifth quintiles of fat mass. In the case of polychlorinated biphenyls, the mortality in the highest quintile of fat mass was only one-fifth of that in the lowest quintile.

    CONCLUSION: These findings are consistent with our hypothesis that adipose tissue provides relatively safe storage of toxic lipophilic chemicals, a phenomenon that could explain the obesity paradox. Although weight loss may be beneficial among the obese elderly with low POP concentrations, weight loss in the obese elderly with higher serum concentrations of POPs may carry some risk.

  • 166.
    Horikoshi, Momoko
    et al.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Maegi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Surakka, Ida
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Sarin, Antti-Pekka
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Marullo, Letizia
    Univ Ferrara, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy..
    Thorleifsson, Gudmar
    deCode Genet Amgen Inc, Reykjavik, Iceland..
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Ladenvall, Claes
    Skane Univ Hosp, Lund Univ Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany..
    Willems, Sara M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Beekman, Marian
    Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.;Netherlands Consortium Hlth Ageing, Leiden, Netherlands..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth Res, Leicester Cardiovasc Dis Biomed Res Unit, Glenfield Hosp, Leicester, Leics, England..
    Willenborg, Christina
    Univ Lubeck, Inst Integrat & Expt Gen, Lubeck, Germany.;DZHK German Ctr Cardiovascular Res, Lubeck, Germany..
    Wiltshire, Steven
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Fernandez, Juan
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Steinthorsdottir, Valgerdur
    deCode Genet Amgen Inc, Reykjavik, Iceland..
    Hamsten, Anders
    Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Cardiovascular Genet & Genom Grp, Stockholm, Sweden..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Milaneschi, Yuri
    Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Groves, Christopher J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Bennett, Amanda J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Lehtimaeki, Terho
    Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland.;Univ Tampere, Sch Med, FIN-33101 Tampere, Finland..
    Viikari, Jorma S.
    Univ Turku, Dept Med, Turku, Finland.;Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland..
    Rung, Johan
    European Bioinformat Inst, European Mol Biol Lab, Hinxton, England..
    Lyssenko, Valeriya
    Skane Univ Hosp, Lund Univ Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Steno Diabet Ctr AS, Gentofte, Denmark..
    Perola, Markus
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany..
    Herder, Christian
    Univ Dusseldorf, Leibniz Inst Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD eV, Partner Dusseldorf, Dusseldorf, Germany..
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Inst Med Informat,Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany..
    Roden, Michael
    Univ Dusseldorf, Leibniz Inst Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD eV, Partner Dusseldorf, Dusseldorf, Germany.;Univ Hosp Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Hypponen, Elina
    Univ S Australia, Sch Populat Hlth, Adelaide, SA 5001, Australia.;UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England..
    Isaacs, Aaron
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.;Ctr Med Syst Biol, Leiden, Netherlands..
    van Leeuwen, Elisabeth M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Karssen, Lennart C.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Houwing-Duistermaat, Jeanine J.
    Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands..
    de Craen, Anton J. M.
    Netherlands Consortium Hlth Ageing, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Deelen, Joris
    Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.;Netherlands Consortium Hlth Ageing, Leiden, Netherlands..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland..
    Blades, Matthew
    Univ Leicester, Bioinformat & Biostatist Support Hub, Leicester, Leics, England..
    Hengstenberg, Christian
    Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Gen, Lubeck, Germany.;DZHK German Ctr Cardiovascular Res, Lubeck, Germany..
    Schunkert, Heribert
    Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Kaprio, Jaakko
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England.;Natl Inst Hlth Res, Leicester Resp Biomed Res Unit, Glenfield Hosp, Leicester, Leics, England..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth Res, Leicester Cardiovasc Dis Biomed Res Unit, Glenfield Hosp, Leicester, Leics, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst Harvard & MIT, Broad Inst, Cambridge, MA USA..
    Slagboom, P. Eline
    Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.;Netherlands Consortium Hlth Ageing, Leiden, Netherlands..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.;Ctr Med Syst Biol, Leiden, Netherlands..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Vasa Cent Hosp, Vaasa, Finland.;Natl Inst Hlth & Welf, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Gieger, Christian
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Jula, Antti
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland..
    Groop, Leif
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Skane Univ Hosp, Lund Univ Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Raitakari, Olli T.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.;Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland.;Turku Univ Hosp, FIN-20520 Turku, Finland..
    Power, Chris
    UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands..
    de Geus, Eco
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Smit, Johannes H.
    Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Thorsteinsdottir, Unnur
    deCode Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Stefansson, Kari
    deCode Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Wellcome Trust Sanger Inst, Cambridge, England..
    Prokopenko, Inga
    Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, Sch Publ Hlth, London, England..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England.;Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England..
    Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation2015Inngår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, nr 7, artikkel-id e1005230Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency >= 0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

  • 167. Hruby, Adela
    et al.
    Ngwa, Julius S.
    Renstrom, Frida
    Wojczynski, Mary K.
    Ganna, Andrea
    Hallmans, Goran
    Houston, Denise K.
    Jacques, Paul F.
    Kanoni, Stavroula
    Lehtimaki, Terho
    Lemaitre, Rozenn N.
    Manichaikul, Ani
    North, Kari E.
    Ntalla, Ioanna
    Sonestedt, Emily
    Tanaka, Toshiko
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    Djousse, Luc
    Grigoriou, Efi.
    Johansson, Ingegerd
    Lohman, Kurt K.
    Pankow, James S.
    Raitakari, Olli T.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Yannakoulia, Mary
    Zillikens, M. Carola
    Hassanali, Neelam
    Liu, Yongmei
    Mozaffarian, Dariush
    Papoutsakis, Constantina
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Uitterlinden, Andre G.
    Viikari, Jorma
    Groves, Christopher J.
    Hofman, Albert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    McCarthy, Mark I.
    Mikkila, Vera
    Mukamal, Kenneth
    Franco, Oscar H.
    Borecki, Ingrid B.
    Cupples, L. Adrienne
    Dedoussis, George V.
    Ferrucci, Luigi
    Hu, Frank B.
    Ingelsson, Erik
    Kahonen, Mika
    Kao, W. H. Linda
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Prokopenko, Inga
    Rotter, Jerome I.
    Siscovick, David S.
    Witteman, Jacqueline C. M.
    Franks, Paul W.
    Meigs, James B.
    McKeown, Nicola M.
    Nettleton, Jennifer A.
    Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies2013Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, nr 3, s. 345-353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

  • 168.
    Huang, Biying
    et al.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94304 USA.;Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden..
    Svensson, Per
    Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden..
    Sundstrom, Johan
    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.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94304 USA.
    Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies2016Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 52-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). Methods: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. Results: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p<0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease. Conclusions: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 169. Huang, X.
    et al.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    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 medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Stenvinkel, P.
    Lindholm, B.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Carrero, J. J.
    Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 1, s. 71-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    The causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD.

    Subjects

    Two population-based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C-estimated glomerular filtration rate <60 mL min−1/1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively.

    Design

    Factor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp.

    Results

    Factor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n-3 polyunsaturated fatty acid (n-3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44–0.81] and 0.45 (95% CI 0.30–0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C-reactive protein. The n-3 PUFA pattern was not consistently associated with these risk factors.

    Conclusions

    A serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.

  • 170.
    Hägg, Sara
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ploner, Alexander
    Maegi, Reedik
    Fischer, Krista
    Draisma, Harmen H. M.
    Kals, Mart
    de Vries, Paul S.
    Dehghan, Abbas
    Willems, Sara M.
    Sarin, Antti-Pekka
    Kristiansson, Kati
    Nuotio, Marja-Liisa
    Havulinna, Aki S.
    de Bruijn, Renee F. A. G.
    Ikram, M. Arfan
    Kuningas, Maris
    Stricker, Bruno H.
    Franco, Oscar H.
    Benyamin, Beben
    Gieger, Christian
    Hall, Alistair S.
    Huikari, Ville
    Jula, Antti
    Jarvelin, Marjo-Riitta
    Kaakinen, Marika
    Kaprio, Jaakko
    Kobl, Michael
    Mangino, Massimo
    Nelson, Christopher P.
    Palotie, Aarno
    Samani, Nilesh J.
    Spector, Tim D.
    Strachan, David P.
    Tobin, Martin D.
    Whitfield, John B.
    Uitterlinden, Andre G.
    Salomaa, Veikko
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kuulasmaa, Kari
    Magnusson, Patrik K.
    Esko, Tonu
    Hofman, Albert
    de Geus, Eco J. C.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Perola, Markus
    Evans, Alun
    Ferrieres, Jean
    Virtamo, Jarmo
    Kee, Frank
    Tregouet, David-Alexandre
    Arveiler, Dominique
    Amouyel, Philippe
    Gianfagna, Francesco
    Brambilla, Paolo
    Ripatti, Samuli
    van Duijn, Cornelia M.
    Metspalu, Andres
    Prokopenko, Inga
    McCarthy, Mark I.
    Pedersen, Nancy L.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Adiposity as a cause of cardiovascular disease: a Mendelian randomization study2015Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, nr 2, s. 578-586Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

  • 171.
    Hänni, Arvo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Fugmann, Andreas
    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.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Systolic blood pressure alterations during hyperinsulinemia are related to changes in ionized calcium status2001Inngår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 14, nr 11 Pt 1, s. 1106-1111Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A correlation between changes in ionized calcium status and changes in systolic blood pressure (BP) has previously been observed during induced euglycemic hyperinsulinemia in patients with essential hypertension. The objective of this study was to evaluate associations between alterations in ion status and BP changes during euglycemic hyperinsulinemia in healthy normotensive subjects. METHODS: Ion status in plasma and BP were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 41 healthy normotensive volunteers. RESULTS: During euglycemic hyperinsulinemia plasma sodium increased by 1% (P < .0001), ionized calcium (iCa) by 5% (P < .0001), and ionized magnesium (iMg) by 4% (P < .01), whereas potassium decreased by 10% (P < .0001). The changes in plasma iCa and iMg correlated significantly to changes in systolic BP (r = -0.38, P < .02; r = -0.32, P < .05, respectively), but the correlation between changes in iMg and changes in systolic BP did not remain significant in a multiple regression model. The glucose infusion rate correlated inversely to the change in iMg (r = -0.39, P < .01). CONCLUSIONS: The group mean systolic BP was unaltered during induced euglycemic hyperinsulinemia in healthy normotensive subjects; however, a more pronounced increase in the circulating iCa concentration was associated with a greater decline in systolic BP, which is in accordance with previous observations in patients with essential hypertension. The group mean diastolic BP was decreased; however, the lowered diastolic BP was not correlated to changes in ion status.

  • 172.
    Imamura, Fumiaki
    et al.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.
    Fretts, Amanda
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Marklund, Matti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Korat, Andres V. Ardisson
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.
    Yang, Wei-Sin
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan.
    Lankinen, Maria
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Qureshi, Waqas
    Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Bowman Gray Ctr,Sect Cardiovasc Med, Winston Salem, NC 27103 USA.
    Helmer, Catherine
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, UMR 1219, Bordeaux, France.
    Chen, Tzu-An
    USDA ARS, Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX USA.
    Wong, Kerry
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia.
    Bassett, Julie K.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia.
    Murphy, Rachel
    Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Ctr Excellence Canc Prevent, Vancouver, BC, Canada.
    Tintle, Nathan
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Yu, Chaoyu Ian
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
    Brouwer, Ingeborg A.
    Vrije Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Fac Earth & Life Sci, Dept Hlth Sci, Amsterdam, Netherlands.
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan.
    Frazier-Wood, Alexis C.
    USDA ARS, Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX USA.
    del Gobbo, Liana C.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA USA.
    Djousse, Luc
    Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Ctr Epidemiol & Biostat, Parkville, Vic, Australia.
    de Goede, Janette
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Gudnason, Vilmundur
    Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
    Harris, William S.
    Univ South Dakota, Sanford Sch Med, Dept Internal Med, Sioux Falls, SD USA;OmegaQuant Analyt LLC, Sioux Falls, SD USA.
    Hodge, Allison
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Ctr Epidemiol & Biostat, Parkville, Vic, Australia.
    Hu, Frank
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.
    Koulman, Albert
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England;Univ Cambridge, Addenbrookes Hosp, Natl Inst Hlth Res Biomed Res Ctr Core Nutr Bioma, Cambridge, England;Univ Cambridge, Addenbrookes Hosp, Natl Inst Hlth Res Biomed Res Ctr Core Metabol &, Cambridge, England;MRC, Elsie Widdowson Lab, Cambridge, England;Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.
    Laakso, Markku
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    McKnight, Barbara
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
    Rajaobelina, Kalina
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, UMR 1219, Bordeaux, France.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala Univ, Dept Publ Hlth & Caring Sci, Clin Nutr & Metab, Uppsala, Sweden.
    Robinson, Jennifer G.
    Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA;Univ Iowa, Dept Med, Coll Publ Hlth, Iowa City, IA 52242 USA.
    Samieri, Cecilia
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, UMR 1219, Bordeaux, France.
    Siscovick, David S.
    New York Acad Med, New York, NY USA.
    Soedamah-Muthu, Sabita S.
    Tilburg Univ, Ctr Res Psychol Somat Dis, Dept Med & Clin Psychol, Tilburg, Netherlands.
    Sotoodehnia, Nona
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Uusitupa, Matti
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Wagenknecht, Lynne E.
    Wake Forest Sch Med, Publ Hlth Sci, Winston Salem, NC USA.
    Wareham, Nick J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.
    Wu, Jason H. Y.
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Forouhi, Nita G.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies2018Inngår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, nr 10, artikkel-id e1002670Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15: 0 and 17: 0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, tri-glycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men ((pinteraction) < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. Conclusions In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

  • 173.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Arnlöv, Johan
    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.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Metabolic syndrome and risk for heart failure in middle-aged men2006Inngår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 92, nr 10, s. 1409-1413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To explore metabolic syndrome as a possible risk factor for development of heart failure (HF).

    Design: Community-based cohort study.

    Setting: Uppsala, Sweden.

    Participants: 2314 50-year-old men free from HF, myocardial infarction and valvular disease at baseline were enrolled between 1970 and 1974 and were followed up until the age of 70. A modified National Cholesterol Education Program definition of metabolic syndrome was used with body mass index in the place of waist circumference.

    Main outcome measure: First hospitalisation for HF.

    Results: In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, ECG left ventricular hypertrophy, smoking and body mass index), the presence at baseline of metabolic syndrome (hazard ratio 1.66, 95% confidence interval (CI) 1.02 to 2.70) was a predictor of subsequent HF. This relation was even stronger after adjustment for the presence of an acute myocardial infarction during follow up in addition to the other established risk factors for HF (hazard ratio 1.80, 95% CI 1.11 to 2.91).

    Conclusion: Metabolic syndrome was a significant predictor of HF, independent of established risk factors for HF including an interim myocardial infarction, during two decades of follow up in a community-based sample of middle-aged men. This implies that metabolic syndrome provides important risk information beyond that of established risk factors for HF.

  • 174.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Björklund-Bodegård, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Diurnal blood pressure pattern and risk of congestive heart failure2006Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 295, nr 24, s. 2859-2866Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: High blood pressure is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal blood pressure pattern to risk of subsequent CHF is unknown.

    OBJECTIVES: To explore 24-hour ambulatory blood pressure characteristics as predictors of CHF incidence and to investigate whether altered diurnal blood pressure patterns confer any additional risk information beyond that provided by conventional office blood pressure measurements.

    DESIGN, SETTING, AND PARTICIPANTS: Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed up until the end of 2002. Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline, and the blood pressure variables were analyzed as predictors of subsequent CHF.

    MAIN OUTCOME MEASURE: First hospitalization for CHF.

    RESULTS: Seventy men developed heart failure during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic blood pressure (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.02-1.55) and the presence of "nondipping" blood pressure (night-day ambulatory blood pressure ratio > or =1; HR, 2.29; 95% CI, 1.16-4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic blood pressures, nondipping blood pressure remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12-4.36 vs normal night-day pattern). Nighttime ambulatory diastolic blood pressure and nondipping blood pressure were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up.

    CONCLUSIONS: Nighttime blood pressure appears to convey additional risk information about CHF beyond office-measured blood pressure and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.

  • 175.
    Ingelsson, Erik
    et al.
    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.
    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. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sleep disturbances independently predict heart failure in overweight middle-aged men2007Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 9, nr 2, s. 184-190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Sleep disturbances are associated with manifest heart failure (HF). However, the relationship between sleep disturbances and incident HF has been less studied. AIMS: To investigate self-reported sleep disturbances as predictors of HF in a longitudinal, community-based cohort of 2314 middle-aged men. METHODS AND RESULTS: Data on self-reported sleep disturbances, as well as established risk factors for HF were collected and analyzed using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF, the presence at baseline of sleep disturbances (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.16-1.99; p=0.002) was an independent risk factor for HF. There was evidence of effect modification between BMI and sleep disturbances. In multivariable-adjusted models, sleep disturbance (HR, 1.58; 95% CI, 1.13-2.21; p=0.008) was an independent risk factor for HF in overweight participants (BMI>25), but not in normal-weight participants (BMI< or =25). All results remained similar in a sub-sample excluding all participants suffering from a myocardial infarction during follow-up. CONCLUSIONS: Self-reported sleep disturbances imply an increased risk of subsequent HF in overweight middle-aged men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction.

  • 176.
    Ingelsson, Erik
    et al.
    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.
    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 folkhälso- och vårdvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Socioeconomic factors as predictors of incident heart failure2006Inngår i: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 12, nr 7, s. 540-545Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Studies of socioeconomic factors as predictors of heart failure (HF) are few and have given opposing results. Further, it is unknown if these factors predict incident HF independently of myocardial infarction and other established risk factors for HF.

    METHODS AND RESULTS: In a community-based cohort of 2314 middle-age men free from HF, valvular disease, and previous myocardial infarction at baseline, socioeconomic factors were examined as predictors for HF using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, serum cholesterol, and interim myocardial infarction), low occupational classification (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.03-2.35 for low vs. high occupational classification), low education level (HR 1.98, 95% CI 1.07-3.68 for elementary school vs. college exam) and being unmarried (HR 1.44, 95% CI 0.99-2.10 for being unmarried vs. being married) increased the risk of HF.

    CONCLUSION: High occupational classification and high education level decreased, and being unmarried increased, the risk of subsequent HF in middle-age men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction. Further studies are needed to understand the mechanisms behind these associations.

  • 177.
    Ingelsson, Erik
    et al.
    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 folkhälso- och vårdvetenskap, Geriatrik. 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.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men2007Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, nr 14, s. 1739-1745Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims To investigate associations of urinary albumin excretion rate (UAER) and heart failure (HF) incidence in a community-based sample.

    Methods and results In a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER (from timed overnight samples) was analysed with established risk factors for HF [acute MI before baseline, acute MI during follow-up (modelled as a time-dependent covariate), hypertension, diabetes, left ventricular hypertrophy, smoking, body mass index, and glomerular filtration rate] and more recently described risk factors [high-sensitive C-reactive protein and insulin sensitivity (clamp glucose disposal rate)] as predictors of HF incidence.

    Ninety-eight participants developed HF during a median follow-up of 9.0 years. In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in individuals without anti-hypertensive treatment (hazard ratio 1.49; 95% CI 1.13–1.98; P = 0.005). Furthermore, UAER remained an independent predictor of HF, also in participants without diabetes at baseline or myocardial infarction at baseline or during follow-up. There were no significant associations between UAER and HF incidence in individuals with anti-hypertensive treatment.

    Conclusion Our observations support the notion that low-grade albuminuria is a marker for subclinical cardiovascular damage that predisposes to future HF in the community.

  • 178.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap. 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. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Insulin resistance and risk of congestive heart failure2005Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 294, nr 3, s. 334-41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. OBJECTIVE: To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. DESIGN, SETTING, AND PARTICIPANTS: The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (>or=70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. MAIN OUTCOME MEASURE: First hospitalization for heart failure. RESULTS: One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. CONCLUSIONS: Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.

  • 179.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Inflammation, as measured by the erythrocyte sedimentation rate, is an independent predictor for the development of heart failure2005Inngår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 45, nr 11, s. 1802-1806Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Our objective was to explore inflammation, measured as erythrocyte sedimentation rate (ESR), as a predictor for the development of heart failure (HF).

    BACKGROUND: In recent years, evidence of the importance of inflammation in the pathophysiology of HF has emerged, and various inflammatory markers have been found to predict future HF. Erythrocyte sedimentation rate is an inexpensive and easily accessible marker of systemic inflammation, but to this date it is unknown whether ESR predicts subsequent HF.

    METHODS: In a community-based prospective study of 2,314 middle-aged men free from HF, myocardial infarction, and valvular disease at baseline, ESR was analyzed in multivariable models together with established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) and hematocrit.

    RESULTS: A total of 282 men developed HF during a median follow-up time of 30 years. In Cox proportional hazards analyses, ESR was an independent predictor of HF (hazard ratio 1.46 for highest quartile vs. the lowest, 95% confidence interval 1.04 to 2.06). This observation remained significant when also adjusting for interim myocardial infarction during follow-up.

    CONCLUSIONS: Erythrocyte sedimentation rate was a significant predictor of HF, independent of established risk factors for HF, and interim myocardial infarction after three decades of follow-up in a population-based sample of middle-aged men. Our findings indicate that inflammation occurs early in the process leading to HF and that ESR could be used to evaluate this process.

  • 180.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    The validity of a diagnosis of heart failure in a hospital discharge register2005Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 7, nr 5, s. 787-791Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: The accuracy of a diagnosis of heart failure (HF) in hospital discharge registers is largely unknown. We aimed to determine the validity of such a diagnosis in the Swedish hospital discharge register.

    METHODS AND RESULTS: In a population-based study of 2322 middle-aged men (the ULSAM study), 321 participants were diagnosed with HF according to the Swedish hospital discharge register, during a median follow-up time of 29 years. A review board examined the validity of the diagnosis according to the European Society of Cardiology definition of HF. Eighty-two percent of the possible cases were classified as having definite HF. An echocardiographic examination increased the validity to 88%. For patients treated at an internal medicine or cardiology clinic the validity was 86% and 91%, respectively. If HF was the primary diagnosis, the validity was 95%, irrespective of clinic type.

    CONCLUSION: The HF diagnosis in the Swedish hospital discharge register appears slightly less precise than for acute myocardial infarction and stroke. For population-based research, only those with a primary diagnosis of HF in the hospital discharge register should be regarded as definite HF cases, or alternatively the cases should be validated individually.

  • 181.
    Jacobsson, Josefin A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sällman Almén, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Hedberg, Lilia A.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Brooks, Samantha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    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.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 5, s. e20158-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

     The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.

    Objective

    To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

    Design

    Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

    Results

     Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

    Conclusions

    Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

  • 182. Jayasinghe, Saroj
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    High serum levels of p,p'-DDE are associated with an accelerated decline in GFR during 10 years follow-up.2018Inngår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 644, s. 371-374Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Over the past 20 years, the global incidence of chronic kidney disease (CKD) has been increasing and organochlorine pesticides (such as DDT) is a suspected etiological factor. The present study examines the associations between low level background exposure to p,p'-DDE (1-dichloro-2,2-bis (p-chlorophenyl) ethylene), the main DDT metabolite, and kidney function during a 10-year follow-up. Data was analysed from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1016, 50% women, all aged 70 years). Serum levels of p,p'-DDE was measured by gas chromatography coupled to high-resolution mass spectrometry (GC/HRMS) at baseline (i.e. age of 70 years). Glomerular filtration rate (GFR) was estimated using serum creatinine and cystatin C at 70, 75 and 80 years of age. A significant decline in GFR was seen during the 10-year follow-up (-24 ml/min/1.73 m2, p < 0.0001). A significant negative interaction was seen between baseline p,p'-DDE levels and change in GFR over time (p < 0.0001) following adjustment for sex, systolic blood pressure, diabetes, BMI, smoking and education level at age 70. Subjects with the lowest levels of p,p'-DDE levels at age 70 showed the lowest decline in GFR over 10 years, while subjects with the highest p,p'-DDE levels showed the greatest decline. Baseline levels of p,p'-DDE were related to an accelerated reduction in GFR over 10 years suggesting a nephrotoxic effect of DDT/p,p'-DDE. These findings support a potential role for DDT in the epidemic of CKD of unknown etiology (CKDu) in agricultural communities of Sri Lanka and Central America where DDT was previously used.

  • 183. Jia, T
    et al.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lindholm, B
    Larsson, T E
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Carrero, J J
    Dietary acid load, kidney function, osteoporosis, and risk of fractures in elderly men and women2015Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 26, nr 2, s. 563-570Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Because kidney dysfunction reduces the ability to excrete dietary acid excess, we hypothesized that underlying kidney function may have confounded the mixed studies linking dietary acid load with the risk of osteoporosis and fractures in the community. In a relatively large survey of elderly men and women, we report that dietary acid load did neither associate with DEXA-estimated bone mineral density nor with fracture risk. Underlying kidney function did not modify these null findings. Our results do not support the dietary acid-base hypothesis of bone loss.

    INTRODUCTION:

    Impaired renal function reduces the ability to excrete dietary acid excess. We here investigate the association between dietary acid load and bone mineral density (BMD), osteoporosis, and fracture risk by renal function status.

    METHODS:

    An observational study was conducted in 861 community-dwelling 70-year-old men and women (49 % men) with complete dietary data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The exposure was dietary acid load as estimated from 7-day food records by the net endogenous acid production (NEAP) and potential renal acid load (PRAL) algorithms. Renal function assessed by cystatin C estimated glomerular filtration rate was reduced in 21 % of the individuals. Study outcomes were BMD and osteoporosis state (assessed by DEXA) and time to fracture (median follow-up of 9.2 years).

    RESULTS:

    In cross-section, dietary acid load had no significant associations with BMD or with the diagnosis of osteoporosis. During follow-up, 131 fractures were validated. Neither NEAP (adjusted hazard ratios (HR) (95 % confidence interval (CI)), 1.01 (0.85-1.21), per 1 SD increment) nor PRAL (adjusted HR (95 % CI), 1.07 (0.88-1.30), per 1 SD increment) associated with fracture risk. Further multivariate adjustment for kidney function or stratification by the presence of kidney disease did not modify these null associations.

    CONCLUSIONS:

    The hypothesis that dietary acid load associates with reduced BMD or increased fracture risk was not supported by this study in community-dwelling elderly individuals. Renal function did not influence on this null finding.

  • 184.
    Jiang, Jiyang
    et al.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.
    Thalamuthu, Anbupalam
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.
    Ho, Jennifer E.
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Ek, Weronica E
    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.
    Brown, David A.
    St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia;Westmead Inst Med Res, Inst Clin Pathol & Med Res, Westmead, NSW, Australia;Westmead Hosp, Westmead, NSW, Australia.
    Breit, Samuel N.
    St Vincents Hosp, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia.
    Wang, Thomas J.
    Vanderbilt Univ, Dept Med, Div Cardiol, Nashville, TN USA.
    Gyllensten, Ulf B.
    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.
    Chen, Ming-Huei
    NHLBI, Populat Sci Branch, NIH, Framingham, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    Enroth, Stefan
    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.
    Januzzi, James L., Jr.
    Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Armstrong, Nicola J.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Murdoch Univ, Math & Stat, Perth, WA, Australia.
    Kwok, John B.
    Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia.
    Schofield, Peter R.
    Neurosci Res Australia, Randwick, NSW, Australia;Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia.
    Wen, Wei
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia.
    Trollor, Julian N.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Univ New South Wales, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Sydney, NSW, Australia.
    Johansson, Åsa
    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.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Vasan, Ramachandran S.
    Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Epidemiol Sect, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Natl Heart Lung & Blood Inst, Boston, MA USA;Boston Univ, Framingham Heart Study, Boston, MA 02215 USA.
    Sachdev, Perminder S.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia;Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia.
    Mather, Karen A.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.
    A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood2018Inngår i: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 9, artikkel-id 97Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of similar to 5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 x 10(-35)), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the "COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.

  • 185.
    Jiang, Xia
    et al.
    Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Dept Epidemiol, 677 Huntington Ave, Boston, MA USA.;Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Nobels Vagen 13, S-17177 Stockholm, Sweden..
    O'Reilly, Paul F.
    Kings Coll London, Inst Psychiat, Dept Social Genet & Dev Psychiat, De Crespigny Pk, London SE5 8AF, England..
    Aschard, Hugues
    Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Dept Epidemiol, 677 Huntington Ave, Boston, MA USA.;Inst Pasteur, Ctr Bioinformat Biostat & Biol Integrat C3BI, F-75724 Paris, France..
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02142 USA..
    Richards, J. Brent
    Dept Med, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.;Dept Human Genet, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.;Dept Epidemiol, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada.;Dept Biostat, 3755 Cote Ste Catherine Rd,Suite H-413, Montreal, PQ H3T 1E2, Canada..
    Dupuis, Josee
    Boston Univ, Dept Biostat, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, USA.
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA..
    Pilz, Stefan
    Med Univ Graz, Div Endocrinol & Diabetol, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria..
    Berry, Diane
    UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St, London WC1E 6BT, England..
    Kestenbaum, Bryan
    Kidney Res Inst, Div Nephrol, 325 Ninth Ave, Seattle, WA 98104 USA..
    Zheng, Jusheng
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England..
    Luan, Jianan
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England..
    Sofianopoulou, Eleni
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England..
    Streeten, Elizabeth A.
    Univ Maryland, Genet & Personalized Med Program, Sch Med, Howard Hall Room 567, Baltimore, MD 21201 USA..
    Albanes, Demetrius
    NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA..
    Lutsey, Pamela L.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300S 2nd St,Suite 300, Minneapolis, MN 55454 USA..
    Yao, Lu
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300S 2nd St,Suite 300, Minneapolis, MN 55454 USA..
    Tang, Weihong
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300S 2nd St,Suite 300, Minneapolis, MN 55454 USA..
    Econs, Michael J.
    Indiana Univ, Dept Med, Endocrinol, 1120W Michigan St, Indianapolis, IN 46202 USA..
    Wallaschofski, Henri
    Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17489 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site, D-13316 Greifswald, Germany..
    Voelzke, Henry
    DZHK German Ctr Cardiovasc Res, Partner Site, D-13316 Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, SHIP Klinisch Epidemiol Forsch, Walther Rathenau Str 48, D-17475 Greifswald, Germany..
    Zhou, Ang
    Univ South Australia, Ctr Populat Hlth Res, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia..
    Power, Chris
    UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St, London WC1E 6BT, England..
    McCarthy, Mark I.
    Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Old Rd, Oxford OX3 7LJ, England.;Univ Oxford, Wellcome Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.;Churchill Hosp, Oxford NIHR Biomed Res Ctr, Old Rd, Oxford OX3 7LJ, England..
    Michos, Erin D.
    Johns Hopkins Sch Med, Ciccarone Ctr Prevent Heart Dis, Div Cardiol, Baltimore, MD 21287 USA.;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA..
    Weinstein, Stephanie J.
    NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA..
    Freedman, Neal D.
    NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA..
    Huang, Wen-Yi
    NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA..
    Van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam Publ Hlth Res Inst, Boelelaan 1089a, NL-1081 HV Amsterdam, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.;AMC, Internal Med, Dept Geriatr, POB 22700, NL-1100 DE Amsterdam, Netherlands..
    de Groot, Lisette C. P. G. M.
    Wageningen Univ, Dept Human Nutr, POB 176700, NL-700 AA Wageningen, Netherlands..
    Enneman, Anke
    Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Cupples, L. Adrienne
    Boston Univ, Dept Biostat, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA..
    Booth, Sarah L.
    Tufts Univ, Vitamin K Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA..
    Vasan, Ramachandran S.
    Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA..
    Liu, Ching-Ti
    Boston Univ, Dept Biostat, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA..
    Zhou, Yanhua
    Boston Univ, Dept Biostat, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA..
    Ripatti, Samuli
    Univ Helsinki, Stat & Translat Genet, Biomedicum, Tukholmankatu 8, Helsinki 2U, Finland..
    Ohlsson, Claes
    Univ Gothenburg, Dept Internal Med & Clin Nutr, Vita Straket 11, S-41345 Gothenburg, Sweden..
    Vandenput, Liesbeth
    Univ Gothenburg, Dept Internal Med & Clin Nutr, Vita Straket 11, S-41345 Gothenburg, Sweden..
    Lorentzon, Mattias
    Univ Gothenburg, Dept Geriatr Med, S-43180 Molndal, Sweden.;Sahlgrens Univ Hosp, S-43180 Molndal, Sweden..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, POB 20,Tukholmankatu 8 B, FIN-00014 Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, POB 20,Tukholmankatu 8 B, FIN-00014 Helsinki, Finland.;Univ Helsinki, Folkhalsan Res Ctr, POB 2000014, Helsinki, Finland..
    Shea, M. Kyla
    Tufts Univ, Vitamin K Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA..
    Houston, Denise K.
    Wake Forest Sch Med, Sticht Ctr Healthy Aging & Alzheimers Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA..
    Kritchevsky, Stephen B.
    Wake Forest Sch Med, Sticht Ctr Healthy Aging & Alzheimers Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA..
    Lohman, Kurt K.
    Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA..
    Ferrucci, Luigi
    NIA, Longitudinal Studies Sect, Intramural Res Program, NIH, Baltimore, MD 21225 USA..
    Peacock, Munro
    Indiana Univ, Dept Med, Endocrinol, 1120W Michigan St, Indianapolis, IN 46202 USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Mol Epidemiol, AME, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany..
    Beekman, Marian
    Leiden Univ, Mol Epidemiol, Med Ctr, Einthovenweg 20, NL-2333 ZC Leiden, Netherlands..
    Slagboom, Eline
    Leiden Univ, Mol Epidemiol, Med Ctr, Einthovenweg 20, NL-2333 ZC Leiden, Netherlands..
    Deelen, Joris
    Leiden Univ, Mol Epidemiol, Med Ctr, Einthovenweg 20, NL-2333 ZC Leiden, Netherlands.;Max Planck Inst Biol Ageing, Joseph Stelzmann Str 9b, D-50931 Cologne, Germany..
    van Heemst, Diana
    Leiden Univ, Gerontol & Geriatr, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Theodor Kutzer Ufer1, D-68167 Mannheim, Germany..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Theodor Kutzer Ufer1, D-68167 Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Auenbruggerpl 15, A-8036 Graz, Austria.;SYNLAB Holding Deutschland GmbH, Gubener Str 39, D-86156 Augsburg, Germany..
    de Boer, Ian H.
    Univ Washington, Div Nephrol, 325 Ninth Ave, Washington, DC 98104 USA.;Univ Washington, Kidney Res Inst, 325 Ninth Ave, Washington, DC 98104 USA..
    Wood, Alexis C.
    ARS, USDA, Childrens Nutr Res Ctr, 1100 Bates Ave, Houston, TX 77071 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Rich, Stephen S.
    Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA..
    Robinson-Cohen, Cassianne
    Vanderbilt Univ, Div Nephrol, Dept Med, Med Ctr, 1161 21st Ave S, Nashville, TN 37232 USA..
    den Heijer, Martin
    Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Epidemiol & Biostat Sch Publ Hlth, 156 Norfolk Pl,St Marys Campus, London W2 1PG, England.;Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu 90014, Finland.;Univ Oulu, Bioctr Oulu, POB 5000,Aapistie 5A, FI-90014 Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50 POB 20,90029 OYS, FI-90220 Oulu, Finland..
    Cavadino, Alana
    UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St, London WC1E 6BT, England.;Queen Mary Univ London, Ctr Environm & Prevent Med, Wolfson Inst Prevent Med, Barts & London Sch Med & Dent, Charterhouse Sq, London EC1M 6BQ, England..
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland..
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, MRC Inst Genet Mol Med, Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hayward, Caroline
    Univ Edinburgh, MRC Inst Genet Mol Med, Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Trompet, Stella
    Leiden Univ, Gerontol & Geriatr, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Dept Cardiol, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Broer, Linda
    Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Zgaga, Lina
    Univ Dublin, Trinity Coll Dublin, Dept Publ Hlth & Primary Care, Inst Populat Hlth, D02 PN40, Dublin 24, Ireland..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Theodoratou, Evropi
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Farrington, Susan M.
    Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Timofeeva, Maria
    Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Dunlop, Malcolm G.
    Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Valdes, Ana M.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus,Westminster Bridge Rd, London SE1 7EH, England.;Univ Nottingham, Sch Med, City Hosp, Hucknall Rd, Nottingham NG5 1PB, England..
    Tikkanen, Emmi
    Univ Helsinki, FIMM Inst Mol Med Finland, POB 20, FI-00014 Helsinki, Finland..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere 33014, Finland..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere 33014, Finland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Dept Clin Physiol, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere 33014, Finland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland..
    Mikkila, Vera
    Acad Finland, Hakaniemenranta 6,POB 131, FI-00531 Helsinki, Finland..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands..
    Sattar, Naveed
    BHF Glasgow Cardiovasc Res Ctr, Fac Med, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland..
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England..
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England..
    Forouhi, Nita G.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge CB2 0QQ, England..
    Gundersen, Thomas E.
    Vitas AS, Gaustadaleen 21, N-0349 Oslo, Norway..
    Khaw, Kay-Tee
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England..
    Butterworth, Adam S.
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England..
    Danesh, John
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Worts Causeway, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Spector, Timothy
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus,Westminster Bridge Rd, London SE1 7EH, England..
    Wang, Thomas J.
    Vanderbilt Heart & Vasc Inst, Div Cardiovasc Med, 2220 Pierce Ave 383 Preston Res Bldg, Nashville, TN 37232 USA..
    Hypponen, Elina
    UCL, Populat Policy & Practice, Inst Child Hlth, Great Ormond St, London WC1E 6BT, England.;Univ South Australia, Ctr Populat Hlth Res, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia..
    Kraft, Peter
    Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Dept Epidemiol, 677 Huntington Ave, Boston, MA USA..
    Kiel, Douglas P.
    Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst Harvard & Massachusetts Inst Technol, Boston, MA 02142 USA..
    Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikkel-id 260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

  • 186.
    Johansson, Kristina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wahlqvist, Inger
    von zur Mühlen, Bengt
    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.
    Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1) receptors, as well as brachial plexus blockade, on endothelium-dependent vasodilation in the human forearm2002Inngår i: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 29, nr 7, s. 603-607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    1. The aim of the present study was to investigate the effects of alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol), neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose-response curve for both EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm.

  • 187. Joshi, Peter K
    et al.
    Esko, Tonu
    Mattsson, Hannele
    Eklund, Niina
    Gandin, Ilaria
    Nutile, Teresa
    Jackson, Anne U
    Schurmann, Claudia
    Smith, Albert V
    Zhang, Weihua
    Okada, Yukinori
    Stančáková, Alena
    Faul, Jessica D
    Zhao, Wei
    Bartz, Traci M
    Concas, Maria Pina
    Franceschini, Nora
    Enroth, Stefan
    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.
    Vitart, Veronique
    Trompet, Stella
    Guo, Xiuqing
    Chasman, Daniel I
    O'Connel, Jeffrey R
    Corre, Tanguy
    Nongmaithem, Suraj S
    Chen, Yuning
    Mangino, Massimo
    Ruggiero, Daniela
    Traglia, Michela
    Farmaki, Aliki-Eleni
    Kacprowski, Tim
    Bjonnes, Andrew
    van der Spek, Ashley
    Wu, Ying
    Giri, Anil K
    Yanek, Lisa R
    Wang, Lihua
    Hofer, Edith
    Rietveld, Cornelius A
    McLeod, Olga
    Cornelis, Marilyn C
    Pattaro, Cristian
    Verweij, Niek
    Baumbach, Clemens
    Abdellaoui, Abdel
    Warren, Helen R
    Vuckovic, Dragana
    Mei, Hao
    Bouchard, Claude
    Perry, John R B
    Cappellani, Stefania
    Mirza, Saira S
    Benton, Miles C
    Broeckel, Ulrich
    Medland, Sarah E
    Lind, Penelope A
    Malerba, Giovanni
    Drong, Alexander
    Yengo, Loic
    Bielak, Lawrence F
    Zhi, Degui
    van der Most, Peter J
    Shriner, Daniel
    Mägi, Reedik
    Hemani, Gibran
    Karaderi, Tugce
    Wang, Zhaoming
    Liu, Tian
    Demuth, Ilja
    Zhao, Jing Hua
    Meng, Weihua
    Lataniotis, Lazaros
    van der Laan, Sander W
    Bradfield, Jonathan P
    Wood, Andrew R
    Bonnefond, Amelie
    Ahluwalia, Tarunveer S
    Hall, Leanne M
    Salvi, Erika
    Yazar, Seyhan
    Carstensen, Lisbeth
    de Haan, Hugoline G
    Abney, Mark
    Afzal, Uzma
    Allison, Matthew A
    Amin, Najaf
    Asselbergs, Folkert W
    Bakker, Stephan J L
    Barr, R Graham
    Baumeister, Sebastian E
    Benjamin, Daniel J
    Bergmann, Sven
    Boerwinkle, Eric
    Bottinger, Erwin P
    Campbell, Archie
    Chakravarti, Aravinda
    Chan, Yingleong
    Chanock, Stephen J
    Chen, Constance
    Chen, Y-D Ida
    Collins, Francis S
    Connell, John
    Correa, Adolfo
    Cupples, L Adrienne
    Smith, George Davey
    Davies, Gail
    Dörr, Marcus
    Ehret, Georg
    Ellis, Stephen B
    Feenstra, Bjarke
    Feitosa, Mary F
    Ford, Ian
    Fox, Caroline S
    Frayling, Timothy M
    Friedrich, Nele
    Geller, Frank
    Scotland, Generation
    Gillham-Nasenya, Irina
    Gottesman, Omri
    Graff, Misa
    Grodstein, Francine
    Gu, Charles
    Haley, Chris
    Hammond, Christopher J
    Harris, Sarah E
    Harris, Tamara B
    Hastie, Nicholas D
    Heard-Costa, Nancy L
    Heikkilä, Kauko
    Hocking, Lynne J
    Homuth, Georg
    Hottenga, Jouke-Jan
    Huang, Jinyan
    Huffman, Jennifer E
    Hysi, Pirro G
    Ikram, M Arfan
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Joensuu, Anni
    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.
    Jousilahti, Pekka
    Jukema, J Wouter
    Kähönen, Mika
    Kamatani, Yoichiro
    Kanoni, Stavroula
    Kerr, Shona M
    Khan, Nazir M
    Koellinger, Philipp
    Koistinen, Heikki A
    Kooner, Manraj K
    Kubo, Michiaki
    Kuusisto, Johanna
    Lahti, Jari
    Launer, Lenore J
    Lea, Rodney A
    Lehne, Benjamin
    Lehtimäki, Terho
    Liewald, David C M
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Loh, Marie
    Lokki, Marja-Liisa
    London, Stephanie J
    Loomis, Stephanie J
    Loukola, Anu
    Lu, Yingchang
    Lumley, Thomas
    Lundqvist, Annamari
    Männistö, Satu
    Marques-Vidal, Pedro
    Masciullo, Corrado
    Matchan, Angela
    Mathias, Rasika A
    Matsuda, Koichi
    Meigs, James B
    Meisinger, Christa
    Meitinger, Thomas
    Menni, Cristina
    Mentch, Frank D
    Mihailov, Evelin
    Milani, Lili
    Montasser, May E
    Montgomery, Grant W
    Morrison, Alanna
    Myers, Richard H
    Nadukuru, Rajiv
    Navarro, Pau
    Nelis, Mari
    Nieminen, Markku S
    Nolte, Ilja M
    O'Connor, George T
    Ogunniyi, Adesola
    Padmanabhan, Sandosh
    Palmas, Walter R
    Pankow, James S
    Patarcic, Inga
    Pavani, Francesca
    Peyser, Patricia A
    Pietilainen, Kirsi
    Poulter, Neil
    Prokopenko, Inga
    Ralhan, Sarju
    Redmond, Paul
    Rich, Stephen S
    Rissanen, Harri
    Robino, Antonietta
    Rose, Lynda M
    Rose, Richard
    Sala, Cinzia
    Salako, Babatunde
    Salomaa, Veikko
    Sarin, Antti-Pekka
    Saxena, Richa
    Schmidt, Helena
    Scott, Laura J
    Scott, William R
    Sennblad, Bengt
    Seshadri, Sudha
    Sever, Peter
    Shrestha, Smeeta
    Smith, Blair H
    Smith, Jennifer A
    Soranzo, Nicole
    Sotoodehnia, Nona
    Southam, Lorraine
    Stanton, Alice V
    Stathopoulou, Maria G
    Strauch, Konstantin
    Strawbridge, Rona J
    Suderman, Matthew J
    Tandon, Nikhil
    Tang, Sian-Tsun
    Taylor, Kent D
    Tayo, Bamidele O
    Töglhofer, Anna Maria
    Tomaszewski, Maciej
    Tšernikova, Natalia
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Vaidya, Dhananjay
    van Hylckama Vlieg, Astrid
    van Setten, Jessica
    Vasankari, Tuula
    Vedantam, Sailaja
    Vlachopoulou, Efthymia
    Vozzi, Diego
    Vuoksimaa, Eero
    Waldenberger, Melanie
    Ware, Erin B
    Wentworth-Shields, William
    Whitfield, John B
    Wild, Sarah
    Willemsen, Gonneke
    Yajnik, Chittaranjan S
    Yao, Jie
    Zaza, Gianluigi
    Zhu, Xiaofeng
    Salem, Rany M
    Melbye, Mads
    Bisgaard, Hans
    Samani, Nilesh J
    Cusi, Daniele
    Mackey, David A
    Cooper, Richard S
    Froguel, Philippe
    Pasterkamp, Gerard
    Grant, Struan F A
    Hakonarson, Hakon
    Ferrucci, Luigi
    Scott, Robert A
    Morris, Andrew D
    Palmer, Colin N A
    Dedoussis, George
    Deloukas, Panos
    Bertram, Lars
    Lindenberger, Ulman
    Berndt, Sonja I
    Lindgren, Cecilia M
    Timpson, Nicholas J
    Tönjes, Anke
    Munroe, Patricia B
    Sørensen, Thorkild I A
    Rotimi, Charles N
    Arnett, Donna K
    Oldehinkel, Albertine J
    Kardia, Sharon L R
    Balkau, Beverley
    Gambaro, Giovanni
    Morris, Andrew P
    Eriksson, Johan G
    Wright, Margie J
    Martin, Nicholas G
    Hunt, Steven C
    Starr, John M
    Deary, Ian J
    Griffiths, Lyn R
    Tiemeier, Henning
    Pirastu, Nicola
    Kaprio, Jaakko
    Wareham, Nicholas J
    Pérusse, Louis
    Wilson, James G
    Girotto, Giorgia
    Caulfield, Mark J
    Raitakari, Olli
    Boomsma, Dorret I
    Gieger, Christian
    van der Harst, Pim
    Hicks, Andrew A
    Kraft, Peter
    Sinisalo, Juha
    Knekt, Paul
    Johannesson, Magnus
    Magnusson, Patrik K E
    Hamsten, Anders
    Schmidt, Reinhold
    Borecki, Ingrid B
    Vartiainen, Erkki
    Becker, Diane M
    Bharadwaj, Dwaipayan
    Mohlke, Karen L
    Boehnke, Michael
    van Duijn, Cornelia M
    Sanghera, Dharambir K
    Teumer, Alexander
    Zeggini, Eleftheria
    Metspalu, Andres
    Gasparini, Paolo
    Ulivi, Sheila
    Ober, Carole
    Toniolo, Daniela
    Rudan, Igor
    Porteous, David J
    Ciullo, Marina
    Spector, Tim D
    Hayward, Caroline
    Dupuis, Josée
    Loos, Ruth J F
    Wright, Alan F
    Chandak, Giriraj R
    Vollenweider, Peter
    Shuldiner, Alan R
    Ridker, Paul M
    Rotter, Jerome I
    Sattar, Naveed
    Gyllensten, Ulf
    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.
    North, Kari E
    Pirastu, Mario
    Psaty, Bruce M
    Weir, David R
    Laakso, Markku
    Gudnason, Vilmundur
    Takahashi, Atsushi
    Chambers, John C
    Kooner, Jaspal S
    Strachan, David P
    Campbell, Harry
    Hirschhorn, Joel N
    Perola, Markus
    Polašek, Ozren
    Wilson, James F
    Directional dominance on stature and cognition in diverse human populations2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 523, nr 7561, s. 459-462Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

  • 188. Justice, Anne E.
    et al.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lindgren, Cecilia M.
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 3, s. 452-469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 189.
    Justice, Anne E.
    et al.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Winkler, Thomas W.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Graff, Misa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Fisher, Virginia A.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Young, Kristin
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Barata, Llilda
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Deng, Xuan
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Czajkowski, Jacek
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Hadley, David
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.;TransMed Syst Inc, Cupertino, CA 95014 USA..
    Ngwa, Julius S.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA..
    Ahluwalia, Tarunveer S.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr, Gentofte, Denmark..
    Chu, Audrey Y.
    NHLBI Framingham Heart Study, Framingham, MA 01702 USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Heard-Costa, Nancy L.
    NHLBI Framingham Heart Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Lim, Elise
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Perez, Jeremiah
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Eicher, John D.
    Framingham Heart Dis Epidemiol Study, NIH, Natl Heart Lung & Blood Inst, Populat Sci Branch, Framingham, MA USA..
    Kutalik, Zoltan
    CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.;Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Xue, Luting
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Renstrom, Frida
    Umea Univ, Dept Biobank Res, Umea, Sweden.;Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Wu, Joseph
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Qi, Qibin
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA..
    Ahmad, Shafqat
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Alfred, Tamuno
    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 USA..
    Amin, Najaf
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Bonnefond, Amelie
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Bragg, Jennifer
    Univ Michigan, Internal Med Nephrol, Ann Arbor, MI USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Cadby, Gemma
    Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley 6009, Australia..
    Chittani, Martina
    Univ Milan, Dept Hlth Sci, Via A Di Rudini 8, I-20142 Milan, Italy..
    Coggeshall, Scott
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Corre, Tanguy
    CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.;Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Direk, Nese
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Gorski, Mathias
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Harder, Marie Neergaard
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Horikoshi, Momoko
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England..
    Huang, Tao
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Epidemiol Domain, Singapore 117549, Singapore..
    Huffman, Jennifer E.
    Framingham Heart Dis Epidemiol Study, NIH, Natl Heart Lung & Blood Inst, Populat Sci Branch, Framingham, MA USA.;Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Kinnunen, Leena
    Natl Inst Hlth & Welfare, Dept Hlth, FI-00271 Helsinki, Finland..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Kumari, Meena
    Univ Essex, ISER, Colchester CO4 3SQ, Essex, England.;UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England..
    Lim, Unhee
    Univ Hawaii, Canc Ctr, Epidemiol Program, Honolulu, HI 96813 USA..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere 33014, Finland..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London, England..
    Manichaikul, Ani
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA.;Univ Virginia, Dept Publ Hlth Sci, Biostat Sect, Charlottesville, VA 22903 USA..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Middelberg, Rita P. S.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4029, Australia..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Navarro, Pau
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Perusse, Louis
    Univ Laval, Fac Med, Dept Kinesiol, Quebec City G1V 0A6, PQ, Canada.;Univ Laval, Inst Nutr & Funct Foods, Quebec City G1V 0A6, PQ, Canada..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-51010 Tartu, Estonia..
    Sarti, Cinzia
    Dept Social & Hlth Care, Helsinki, Finland..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Dept Med, Kuopio 70210, Finland..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Sung, Yun Ju
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA..
    Tanaka, Toshiko
    Natl Inst Aging, Translat Gerontol Branch, Baltimore, MD USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Trompet, Stella
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    van der Laan, Sander W.
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Lab Expt Cardiol, Utrecht, Netherlands..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Van Vliet-Ostaptchouk, Jana V.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands..
    Vedantam, Sailaja L.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Broad Inst Harvard, Cambridge, MA 02142 USA..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Vink, Jacqueline M.
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA..
    Yengo, Loic
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Zhang, Weihua
    Imper Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Cardiol, Southall, Middx, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Zimmermann, Martina E.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany..
    Zubair, Niha
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Adair, Linda S.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA..
    Afaq, Saima
    Imper Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Cardiol, Southall, Middx, England..
    Afzal, Uzma
    Imper Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Cardiol, Southall, Middx, England..
    Bakker, Stephan J. L.
    Univ Med Ctr Groningen, Univ Groningen, Dept Med, Groningen, Netherlands..
    Bartz, Traci M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Beilby, John
    Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.;Sir Charles Gairdner Hosp, PathWest Lab Med WA, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Pathol, 35 Stirling Hwy, Crawley, WA 6009, Australia.;Univ Western Australia, Laboraty Med, 35 Stirling Hwy, Crawley, WA 6009, Australia..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA..
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Biffar, Reiner
    Univ Med Greifswald, Clin Prosthet Dent Gerostomatol & Mat Sci, Greifswald, Germany..
    Blangero, John
    Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr, Human Genet Ctr, POB 20186, Houston, TX 77225 USA..
    Bonnycastle, Lori L.
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Bottinger, Erwin
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY USA..
    Braga, Daniele
    Univ Milan, Dept Hlth Sci, Via A Di Rudini 8, I-20142 Milan, Italy..
    Buckley, Brendan M.
    Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland..
    Buyske, Steve
    Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA.;Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ 08854 USA..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Chambers, John C.
    Imper Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Francis S.
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    de Borst, Gert J.
    UMC Utrecht, Dept Vasc Surg, Div Surg Specialties, Utrecht, Netherlands..
    de Craen, Anton J. M.
    Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    de Geus, Eco J. C.
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ, FMGO Inst, Amsterdam, Netherlands.;Vrije Univ, Med Ctr, Amsterdam, Netherlands..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Delgado, Graciela E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    den Ruijter, Hester M.
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Lab Expt Cardiol, Utrecht, Netherlands..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland..
    Eriksson, Anna L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Broad Inst Harvard, Cambridge, MA 02142 USA..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Forrester, Terrence
    Univ West Indies, Trop Med Res Inst, Trop Metab Res Unit, Mona JMAAW15, Jamaica, NY USA..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Glorioso, Nicola
    Univ Sassari, Hypertens & Related Dis Ctr, AOU, Sassari, Italy..
    Gong, Jian
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Grallert, Harald
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;German Ctr Diabet Res, D-85764 Neuherberg, Germany..
    Grammer, Tanja B.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Haitjema, Saskia
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Lab Expt Cardiol, Utrecht, Netherlands..
    Hallmans, Goran
    Umea Univ, Sect Nutr Res, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Hansen, Torben
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England..
    Harris, Tamara B.
    Natl Inst Aging, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Hassinen, Maija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Hastie, Nicholas D.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Heath, Andrew C.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Hernandez, Dena
    Natl Inst Aging, Lab Neurogenet, Bethesda, MD USA..
    Hindorff, Lucia
    Natl Human Genome Res Inst, NIH, Div Genom Med, Bethesda, MD 20892 USA..
    Hocking, Lynne J.
    Univ Aberdeen, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Holmen, Oddgeir L.
    Univ Trondheim Hosp, St Olav Hosp, Trondheim, Norway..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany..
    Hottenga, Jouke Jan
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands..
    Huang, Jie
    Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England..
    Hung, Joseph
    Univ Western Australia, Sch Med & Pharmacol, 25 Stirling Hwy, Crawley, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Cardiovasc Med, Nedlands, WA 6009, Australia..
    Hutri-Kahonen, Nina
    Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Pediat, Tampere 33014, Finland..
    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, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    James, Alan L.
    Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Med & Pharmacol, 25 Stirling Hwy, Crawley, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia..
    Jansson, John-Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Norfolk Pl, London, England.;Univ Oulu, Fac Med, Ctr Life Course Epidemiol, POB 5000, FI-90014 Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50,POB 20, FI-90220 Oulu, Finland..
    Jhun, Min A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Juonala, Markus
    Univ Turku, Dept Med, Turku 20520, Finland.;Turku Univ Hosp, Div Med, Turku 20521, Finland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere 33014, Finland..
    Karlsson, Magnus
    Lund Univ, Skane Univ Hosp, Dept Orthoped & Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welfare, Dept Hlth, FI-00271 Helsinki, Finland.;Univ Helsinki, Endocrinol, Dept Med, FI-00029 Helsinki, Finland.;Univ Helsinki, Endocrinol, Abdominal Ctr, FI-00029 Helsinki, Finland.;Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland.;Minerva Fdn, Biomed 2U, FI-00290 Helsinki, Finland..
    Kolcic, Ivana
    Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Kolovou, Genovefa
    Onassis Cardiac Surg Ctr, Dept Cardiol, Athens, Greece..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Kramer, Bernhard K.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Kvaloy, Kirsti
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, HUNT Res Ctr, N-7600 Levanger, Norway..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Launer, Lenore J.
    Natl Inst Aging, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Lee, Nanette R.
    Univ San Carlos, Off Populat Studies Fdn Inc, Cebu 6000, Philippines.;Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu 6000, Philippines..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England. Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Linneberg, Allan
    Minerva Fdn, Biomed 2U, FI-00290 Helsinki, Finland.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Lobbens, Stephane
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Loh, Marie
    Imper Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;ASTAR, Agcy Sci Technol & Res, Translat Lab Genet Med TLGM, 8A Biomed Grove,Immunos Level 5, Singapore 138648, Singapore..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Luben, Robert
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lubke, Gitta
    Univ Notre Dame, Dept Psychol, Notre Dame, IN 46556 USA..
    Ludolph-Donislawski, Anja
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany..
    Lupoli, Sara
    Univ Milan, Dept Hlth Sci, Via A Di Rudini 8, I-20142 Milan, Italy..
    Madden, Pamela A. F.
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Mannikko, Reija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Marques-Vidal, Pedro
    Lausanne Univ Hosp CHUV, Dept Med Internal Med, Lausanne, Switzerland..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4029, Australia..
    McKenzie, Colin A.
    Univ West Indies, Trop Med Res Inst, Trop Metab Res Unit, Mona JMAAW15, Jamaica, NY USA..
    McKnight, Barbara
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Menni, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld 4029, Australia..
    Musk, A. W. (Bill)
    Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Populat Hlth, 35 Stirling Hwy, Crawley, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia..
    Narisu, Narisu
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Olden, Matthias
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany..
    Ong, Ken K.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Padmanabhan, Sandosh
    Univ Aberdeen, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland.;Univ Glasgow, BHF Glasgow CardiovascRes Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Pisinger, Charlotta
    Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Porteous, David J.
    Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland..
    Rankinen, Tuomo
    Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA..
    Rao, D. C.
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA..
    Rasmussen-Torvik, Laura J.
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA..
    Rawal, Rajesh
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Rice, Treva
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.;Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Bien, Stephanie A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Sanna, Serena
    Cittadella Univ Monserrato, CNR, IRGB, I-09042 Monserrato, Italy..
    Sarzynski, Mark A.
    Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA..
    Sattar, Naveed
    BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland..
    Savonen, Kai
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Schlessinger, David
    Natl Inst Aging, NIH, Lab Genet, Baltimore, MD USA..
    Scholtens, Salome
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Schurmann, Claudia
    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 USA..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Sennblad, Bengt
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Stockholm, Sweden..
    Siemelink, Marten A.
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Lab Expt Cardiol, Utrecht, Netherlands..
    Silbernagel, Gunther
    Med Univ Graz, Dept Internal Med, Div Angiol, Graz, Austria..
    Slagboom, P. Eline
    Leiden Univ, Dept Mol Epidemiol, Med Ctr, Leiden, Netherlands..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Staessen, Jan A.
    Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Campus Sint Rafael,Kapucijnenvoer 35, Leuven, Belgium.;Maastricht Univ, R&D VitaK Grp, Brains Unlimited Bldg,Oxfordlaan 55, Maastricht, Netherlands..
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland..
    Swertz, Morris A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Swift, Amy J.
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Ctr Translat Genom & Populat Sci, Torrance, CA USA.;Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA USA..
    Tayo, Bamidele O.
    Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 61053 USA..
    Thorand, Barbara
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;German Ctr Diabet Res, D-85764 Neuherberg, Germany..
    Thuillier, Dorothee
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Res Div, Kuwait, Kuwait.;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems 3500, Austria. Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.;King Abdulaziz Univ, Saudi Diabet Res Grp, Jeddah, Saudi Arabia..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Vohl, Marie-Claude
    Univ Laval, Inst Nutr & Funct Foods, Quebec City G1V 0A6, PQ, Canada.;Univ Laval, Sch Nutr, Laval, PQ, Canada..
    Volzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Vonk, Judith M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Waeber, Gerard
    Lausanne Univ Hosp CHUV, Dept Med Internal Med, Lausanne, Switzerland..
    Waldenberger, Melanie
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Westendorp, R. G. J.
    Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen, Denmark.;Univ Copenhagen, Ctr Healthy Aging, DK-1014 Copenhagen, Denmark..
    Wild, Sarah
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Willemsen, Gonneke
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands..
    Wolffenbuttel, Bruce H. R.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands..
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England..
    Wright, Alan F.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Balkau, Beverley
    INSERM, U 1018, F-94807 Villejuif, France..
    Bandinelli, Stefania
    Azienda USL Toscana Ctr, Geriatr Unit, Florence, Italy..
    Boger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Boomsma, Dorret I.
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands..
    Bouchard, Claude
    Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA..
    Bruinenberg, Marcel
    Lifelines Cohort Study, POB 30001, NL-9700 RB Groningen, Netherlands..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Chen, Yii-Der Ida
    Univ Calif Los Angeles, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Univ Calif Los Angeles, Dept Pediat Harbor, Torrance, CA 90502 USA..
    Chines, Peter S.
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Cooper, Richard S.
    Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 61053 USA..
    Cucca, Francesco
    Cittadella Univ Monserrato, CNR, IRGB, I-09042 Monserrato, Italy.;Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy..
    Cusi, Daniele
    Sanipedia Srl, Bresso, Milano, Italy.;Inst Biomed Technol Natl Ctr Res Segrate, Milan, Italy..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Ferrucci, Luigi
    Natl Inst Aging, Translat Gerontol Branch, Baltimore, MD USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Froguel, Philippe
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France.;Imperial Coll London, Dept Genom Common Dis, London, England..
    Gordon-Larsen, Penny
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27516 USA..
    Grabe, Hans-Jorgen
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.;German Ctr Neurodegenerat Dis DZNE, Rostock & Greifswald Site, Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Haiman, Christopher A.
    Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, HUNT Res Ctr, N-7600 Levanger, Norway..
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, NIH, Natl Heart Lung & Blood Inst, Populat Sci Branch, Framingham, MA USA..
    Jukema, Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Hammersmith Hosp, Fac Med, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Kuh, Diana
    UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere 33014, Finland..
    Le Marchand, Loic
    Univ Hawaii, Canc Ctr, Epidemiol Program, Honolulu, HI 96813 USA..
    Marz, Winfried
    Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.;Med Univ Graz, Clin Inst Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.;Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res NIHR, Oxford, England..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden..
    Palmer, Lyle J.
    Univ Adelaide, Sch Publ Hlth, Adelaide, SA 5005, Australia..
    Pasterkamp, Gerard
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Lab Expt Cardiol, Utrecht, Netherlands.;UMC Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Peters, Annette
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;German Ctr Diabet Res, D-85764 Neuherberg, Germany..
    Peters, Ulrike
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.;Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Qi, Lu
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Smith, Blair H.
    Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland. Univ Dundee, Ninewells Hosp, Div Populat Hlth Sci, Dundee DD2 4RB, Scotland. Univ Dundee, Med Sch, Dundee DD2 4RB, Scotland..
    Sorensen, Thorkild I. A.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Bispebjerg & Frederiksberg Hosp, Dept Clin Epidemiol, Copenhagen, Denmark.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany..
    Tiemeier, Henning
    Erasmus MC, Dept Psychiat, Rotterdam, Netherlands..
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Van der Harst, Pim
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr, Gentofte, Denmark..
    Vollenweider, Peter
    Lausanne Univ Hosp CHUV, Dept Med Internal Med, Lausanne, Switzerland..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Weir, David R.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA..
    Whitfield, John B.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4029, Australia..
    Wilson, James F.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Tyrrell, Jessica
    Univ Exeter, Med Sch, Genet Complex Traits, RILD Bldg, Exeter EX2 5DW, Devon, England.;Univ Exeter, European Ctr Environm & Human Hlth, Med Sch, Truro TR1 3HD, England..
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Cambridge, England.;Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Box 289,Level 4, Cambridge CB2 OQQ, England.;Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Level 4,Box 289, Cambridge CB2 OQQ, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Deloukas, Panagiotis
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Wellcome Trust Sanger Inst, Cambridge, England.;King Abdulaziz Univ, PACER HD, Jeddah, Saudi Arabia..
    Fox, Caroline S.
    NHLBI Framingham Heart Study, Framingham, MA 01702 USA..
    Hirschhorn, Joel N.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Broad Inst Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA..
    Hunter, David J.
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Broad Inst Harvard, Cambridge, MA 02142 USA.;Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.;St Georges Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England..
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands.;Netherlands Consortium Healthy Aging, Netherlands Genom Initiat, Leiden, Netherlands.;Ctr Med Syst Biol, Leiden, Netherlands..
    Heid, Iris M.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA..
    Marchini, Jonathan
    Univ Oxford, Dept Stat, Oxford, 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, Genet Obes & Related Metab Traits Program, New York, NY USA.;Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.;Mt Sinai Sch Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Kilpelainen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.;Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    North, Kari E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;NHLBI Framingham Heart Study, Framingham, MA 01702 USA..
    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits2017Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikkel-id 14977Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

  • 190.
    Järhult, Susann J
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Johansson, Lars
    Astra Zeneca, R&D, Mölndal.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Brachial artery hyperemic blood flow velocity in relation to established indices of vascular function and global atherosclerosis2012Inngår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, nr 3, s. 227-233Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background

    Systolic to diastolic blood flow velocity (SDFV) ratio in the Brachial artery recently proved to be related to cardiovascular risk and Carotid atherosclerosis. We hypothesized that the SDFV ratio was related to established markers of vascular function and global atherosclerosis. 

     

    Methods

    Established markers of endothelial function in forearm resistance vessels, flow-mediated vasodilation and arterial stiffness were assessed in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study including 1016 individuals aged 70. Whole body magnetic resonance angiography was performed in a random 306 of the participants. Atherosclerotic lesions were summarized in a total atherosclerotic score (TAS). Before and during hyperemia of the Brachial artery, systolic and diastolic blood flow velocities were measured by Doppler.

     

    Results

    The SDFV ratio was positively related to endothelium-independent vasodilatation, while inverse relations to flow-mediated dilation, common carotid artery distensibility and the stroke volume to pulse pressure ratio were found. Endothelium-dependent vasodilatation and total peripheral resistance index were not significantly related to the SDFV ratio.

    The SDFV ratio (p=0.015) and the blood flow increase during hyperemia (p= 0.020) were both significantly related to TAS after gender adjustment. When adjusted for the Framingham risk score, both the SDFV ratio (p= 0.057) and blood flow increase (p= 0.078) lost somewhat in significance.

     

    Conclusion

    The SDFV ratio was related to established markers of both vasodilation and arterial compliance, and to global atherosclerosis. Future larger studies have to evaluate if the SDFV ratio is related to global atherosclerosis independently of traditional risk factors.

  • 191.
    Järhult, Susann J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundström, Johan
    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.
    Brachial artery hyperaemic blood flow velocity and left ventricular geometry2012Inngår i: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 26, nr 4, s. 242-246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiovascular risk factors and carotid atherosclerosis relate to blood flow velocity in the brachial artery during induced hyperaemia. This relation proved to be particularly strong when using the hyperaemic systolic to diastolic blood flow velocity (SDFV) ratio. In this study, we further investigated this ratio in relation to the left ventricular (LV) geometry in a cross-sectional analysis. In the Prospective Investigation of the Vasculature in Uppsala Seniors study, 1016 seventy-year-olds participated. Blood flow velocity during hyperaemia of the brachial artery by Doppler was analysed. Echocardiography was performed, allowing analysis of LV geometry, categorised into four different groups: normal, concentric remodelling, concentric and eccentric hypertrophy. The SDFV ratio increased in subjects with concentric LV-remodelling (P 0.006) or LV-hypertrophy (P=0.001), but not in those with eccentric hypertrophy (P=0.12) when compared with the group with normal LV geometry. These associations remained significant after adjustment for gender, blood pressure, blood glucose, body mass index and antihypertensive treatment. The SDFV ratio in the brachial artery was related to concentric geometry of the LV in an elderly population sample, suggesting this new hemodynamic variable as a marker of increased afterload. Future studies have to determine if the SDFV ratio is a powerful predictor of future CV events, in addition to LV geometry.

  • 192.
    Kamble, Prasad G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Pereira, Maria J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lundkvist, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Cook, Naomi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Franks, Paul W.
    Lund Univ, Diabet Ctr, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers2017Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 4, s. 234-242Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships.

    METHODS: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments.

    RESULTS: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups.

    CONCLUSIONS: Our report highlights that from a practical perspective, GBR can be used to study genotype-phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.

  • 193. Kanoni, Stavroula
    et al.
    Nettleton, Jennifer A.
    Hivert, Marie-France
    Ye, Zheng
    van Rooij, Frank J. A.
    Shungin, Dmitry
    Sonestedt, Emily
    Ngwa, Julius S.
    Wojczynski, Mary K.
    Lemaitre, Rozenn N.
    Gustafsson, Stefan
    Anderson, Jennifer S.
    Tanaka, Toshiko
    Hindy, George
    Saylor, Georgia
    Renstrom, Frida
    Bennett, Amanda J.
    van Duijn, Cornelia M.
    Florez, Jose C.
    Fox, Caroline S.
    Hofman, Albert
    Hoogeveen, Ron C.
    Houston, Denise K.
    Hu, Frank B.
    Jacques, Paul F.
    Johansson, Ingegerd
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Liu, Yongmei
    McKeown, Nicola
    Ordovas, Jose
    Pankow, James S.
    Sijbrands, Eric J. G.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Uitterlinden, Andre G.
    Yannakoulia, Mary
    Zillikens, M. Carola
    Wareham, Nick J.
    Prokopenko, Inga
    Bandinelli, Stefania
    Forouhi, Nita G.
    Cupples, L. Adrienne
    Loos, Ruth J.
    Hallmans, Goran
    Dupuis, Josee
    Langenberg, Claudia
    Ferrucci, Luigi
    Kritchevsky, Stephen B.
    McCarthy, Mark I.
    Ingelsson, Erik
    Borecki, Ingrid B.
    Witteman, Jacqueline C. M.
    Orho-Melander, Marju
    Siscovick, David S.
    Meigs, James B.
    Franks, Paul W.
    Dedoussis, George V.
    Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis2011Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, nr 9, s. 2407-2416Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE

    Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.

    RESEARCH DESIGN AND METHODS

    We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.

    RESULTS

    We observed a significant association of total zinc intake with lower fasting glucose levels (beta-coefficient +/- SE per 1 mg/day of zinc intake: -0.0012 +/- 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (beta-coefficient +/- SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 +/- 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.

    CONCLUSIONS

    Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

  • 194.
    Karasik, David
    et al.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Bar Ilan Univ, Azrieli Fac Med, Safed, Israel.
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Hsu, Yi-Hsiang
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Akesson, Kristina
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;NIHR Cambridge Biomed Res Ctr, Cambridge, England;Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England.
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany.
    Bochud, Murielle
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
    Borecki, Ingrid B.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA;Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Chambers, John C.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Imperial Coll Healthcare NHS Trust, London, England;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London, England;Imperial Coll London, London, England.
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon, South Korea.
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea;Seoul Natl Univ, Coll Med, Neurosci Res Inst, Dept Anat & Cell Biol, Seoul, South Korea;Seoul Natl Univ, Wide River Inst Immunol, Hongcheon, South Korea.
    Chou, Wen-Chi
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Broad Inst, Cambridge, MA USA.
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    de Groot, Lisette C. P. G. M.
    Columbia Univ, Med Ctr, Ctr Translat & Computat Neuroimmunol Neurol, New York, NY USA.
    De Jager, Phillip L.
    Broad Inst, Cell Circuits Program, Cambridge, MA USA;Free Univ Berlin, Humboldt Univ Berlin, Charite Univ Med Berlin, Berlin, Germany.
    Demuth, Ilja
    Berlin Inst Hlth, Berlin, Germany;Wageningen Univ, Div Human Nutr, AFSG, Wageningen, Netherlands.
    Diatchenko, Luda
    Univ North Carolina Chapel Hill, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC USA;McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland.
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Eriksson, Johan G.
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Estrada, Karol
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Biogen Inc, Translat Biol, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Feitosa, Mary F.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA.
    Fu, Mao
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, CCG Type 2 Diabet, Neuherberg, Germany;German Ctr Diabet Res, Neuherberg, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Lenore, Launer J.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, IGMM, Edinburgh, Midlothian, Scotland.
    Hofman, Albert
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
    Huffman, Kim M.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC 27706 USA;Duke Univ, Sch Med, Dept Med, Div Rheumatol, Durham, NC 27706 USA.
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Dept Human Genet, Hannover, Germany.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA USA.
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Jansson, John-Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden.
    Johnson, Toby
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Univ Lausanne, Dept Med Genet, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Biffar, Reiner
    Ernst Moritz Arndt Univ Greifswald, Dept Prosthet Dent Gerodontol & Biomat, Ctr Oral Hlth, Greifswald, Germany.
    Jordan, Joanne M.
    Univ North Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
    Jula, Antti
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Karlsson, Magnus
    Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Kilpelainen, Tuomas O.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England;Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Klopp, Norman
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Koller, Daniel L.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Hammersmith Hosp, Natl Heart & Lung Inst Cardiovasc Sci, Fac Med, Hammersmith Campus, London, England.
    Kraus, William E.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC USA;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC USA.
    Kritchevsky, Stephen
    Wake Forest Sch Med, Sticht Ctr Hlth Aging & Alzheimers Prevent, Winston Salem, NC USA.
    Kutalik, Zoltan
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Helmholtz Zentrum Munchen, CCG Nutrigen & Type 2 Diabet, Neuherberg, Germany;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lahti, Jari
    Univ Helsinki, Helsinki Collegium Adv Studies, Helsinki, Finland.
    Lang, Thomas
    UC San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA USA;UC San Francisco, Sch Dent, San Francisco, CA USA.
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Childrens Hosp Westmead,Ctr Kidney Res, Sydney, NSW, Australia.
    Lill, Christina
    Univ Lubeck, Inst Neurogenet, Lubeck, Germany.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Livshits, Gregory
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden.
    Luan, Jian'an
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Luben, Robert N.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Malkin, Ida
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel.
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, Munich, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England.
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Newman, Anne B.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    O'Connell, Jeffery R.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Palotie, Aarno
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Dept Med Genet, Helsinki, Finland;Univ Cent Hosp, Helsinki, Finland.
    Peacock, Munro
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Perola, Markus
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med, Helsinki, Finland;Diabet & Obes Res Program, Helsinki, Finland;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Raikkonen, Katri
    Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland.
    Ralston, Stuart H.
    Harvard Med Sch, Boston, MA 02115 USA;Western Gen Hosp, MRC Inst Genet & Mol Med, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Hjelt Inst, Helsinki, Finland.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
    Rudan, Igor
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Satterfield, Suzanne
    Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
    Smith, Albert V.
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Smith, Shad B.
    Duke Univ, Dept Anesthesiol, Ctr Translat Pain Med, Durham, NC USA.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Steinhagen-Thiessen, Elisabeth
    Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Streeten, Elizabeth A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Styrkarsdottir, Unnur
    deCODE Genet, Reykjavik, Iceland.
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Thompson, Patricia
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA;SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
    Thomson, Cynthia A.
    Thorleifsson, Gudmar
    deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Tikkanen, Emmi
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Vollenweider, Peter
    Lausanne Univ Hosp, Dept Med Internal Med, Lausanne, Switzerland;Fac Biol & Med, Lausanne, Switzerland.
    Volzke, Henry
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Wactawski-Wende, Jean
    Univ Buffalo SUNY, Dept Epidemiol & Environm Hlth, Buffalo, NY USA.
    Walker, Mark
    Newcastle Univ, Med Sch, Inst Cellular Med Diabetes, Framlington Pl, Newcastle Upon Tyne, Tyne & Wear, England.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Waterworth, Dawn
    GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Weedon, Michael N.
    Univ Exeter, Med Sch, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter, Devon, England.
    Wichmann, H-Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Neuherberg, Germany;Tech Univ, Inst Med Stat & Epidemiol, Munich, Germany.
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Zhang, Weihua
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England.
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Kiel, Douglas P.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Disentangling the genetics of lean mass2019Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, nr 2, s. 276-287Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

  • 195.
    Karlsson, Anders F
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eden Engström, Britt
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Öhrvall, Margareta
    Institutionen för folkhälso- och vårdvetenskap.
    No postprandial increase of plasma adiponectin in obese subjects.2004Inngår i: Obes Res, ISSN 1071-7323, Vol. 12, nr 6, s. 1031-2; author reply 1032Artikkel i tidsskrift (Fagfellevurdert)
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    Carli, Jayne F Martin
    Skowronski, Alicja A
    Sun, Qi
    Kriebel, Jennifer
    Feitosa, Mary F
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Drong, Alexander W
    Hayes, James E
    Zhao, Jinghua
    Pers, Tune H
    Schick, Ursula
    Grarup, Niels
    Kutalik, Zoltán
    Trompet, Stella
    Mangino, Massimo
    Kristiansson, Kati
    Beekman, Marian
    Lyytikäinen, Leo-Pekka
    Eriksson, Joel
    Henneman, Peter
    Lahti, Jari
    Tanaka, Toshiko
    Luan, Jian'an
    Greco M, Fabiola Del
    Pasko, Dorota
    Renström, Frida
    Willems, Sara M
    Mahajan, Anubha
    Rose, Lynda M
    Guo, Xiuqing
    Liu, Yongmei
    Kleber, Marcus E
    Pérusse, Louis
    Gaunt, Tom
    Ahluwalia, Tarunveer S
    Ju Sung, Yun
    Ramos, Yolande F
    Amin, Najaf
    Amuzu, Antoinette
    Barroso, Inês
    Bellis, Claire
    Blangero, John
    Buckley, Brendan M
    Böhringer, Stefan
    I Chen, Yii-Der
    de Craen, Anton J N
    Crosslin, David R
    Dale, Caroline E
    Dastani, Zari
    Day, Felix R
    Deelen, Joris
    Delgado, Graciela E
    Demirkan, Ayse
    Finucane, Francis M
    Ford, Ian
    Garcia, Melissa E
    Gieger, Christian
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hallmans, Göran
    Hankinson, Susan E
    Havulinna, Aki S
    Herder, Christian
    Hernandez, Dena
    Hicks, Andrew A
    Hunter, David J
    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.
    Ioan-Facsinay, Andreea
    Jansson, John-Olov
    Jenny, Nancy S
    Jørgensen, Marit E
    Jørgensen, Torben
    Karlsson, Magnus
    Koenig, Wolfgang
    Kraft, Peter
    Kwekkeboom, Joanneke
    Laatikainen, Tiina
    Ladwig, Karl-Heinz
    LeDuc, Charles A
    Lowe, Gordon
    Lu, Yingchang
    Marques-Vidal, Pedro
    Meisinger, Christa
    Menni, Cristina
    Morris, Andrew P
    Myers, Richard H
    Männistö, Satu
    Nalls, Mike A
    Paternoster, Lavinia
    Peters, Annette
    Pradhan, Aruna D
    Rankinen, Tuomo
    Rasmussen-Torvik, Laura J
    Rathmann, Wolfgang
    Rice, Treva K
    Brent Richards, J
    Ridker, Paul M
    Sattar, Naveed
    Savage, David B
    Söderberg, Stefan
    Timpson, Nicholas J
    Vandenput, Liesbeth
    van Heemst, Diana
    Uh, Hae-Won
    Vohl, Marie-Claude
    Walker, Mark
    Wichmann, Heinz-Erich
    Widén, Elisabeth
    Wood, Andrew R
    Yao, Jie
    Zeller, Tanja
    Zhang, Yiying
    Meulenbelt, Ingrid
    Kloppenburg, Margreet
    Astrup, Arne
    Sørensen, Thorkild I A
    Sarzynski, Mark A
    Rao, D C
    Jousilahti, Pekka
    Vartiainen, Erkki
    Hofman, Albert
    Rivadeneira, Fernando
    Uitterlinden, André G
    Kajantie, Eero
    Osmond, Clive
    Palotie, Aarno
    Eriksson, Johan G
    Heliövaara, Markku
    Knekt, Paul B
    Koskinen, Seppo
    Jula, Antti
    Perola, Markus
    Huupponen, Risto K
    Viikari, Jorma S
    Kähönen, Mika
    Lehtimäki, Terho
    Raitakari, Olli T
    Mellström, Dan
    Lorentzon, Mattias
    Casas, Juan P
    Bandinelli, Stefanie
    März, Winfried
    Isaacs, Aaron
    van Dijk, Ko W
    van Duijn, Cornelia M
    Harris, Tamara B
    Bouchard, Claude
    Allison, Matthew A
    Chasman, Daniel I
    Ohlsson, Claes
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Scott, Robert A
    Langenberg, Claudia
    Wareham, Nicholas J
    Ferrucci, Luigi
    Frayling, Timothy M
    Pramstaller, Peter P
    Borecki, Ingrid B
    Waterworth, Dawn M
    Bergmann, Sven
    Waeber, Gérard
    Vollenweider, Peter
    Vestergaard, Henrik
    Hansen, Torben
    Pedersen, Oluf
    Hu, Frank B
    Eline Slagboom, P
    Grallert, Harald
    Spector, Tim D
    Jukema, J W
    Klein, Robert J
    Schadt, Erik E
    Franks, Paul W
    Lindgren, Cecilia M
    Leibel, Rudolph L
    Loos, Ruth J F
    Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels2016Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikkel-id 10494Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

  • 197.
    Klint, Helén
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Lejonklou, Margareta H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Karimullina, Elina
    University of California, Irvine, Department of Developmental and Cell Biology, Irvine, CA 92697, USA.
    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.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Low-dose exposure to bisphenol A in combination with fructose increases expression of genes regulating angiogenesis and vascular tone in juvenile Fischer 344 rat cardiac tissue2017Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 1, s. 20-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Epidemiological studies report associations between exposure to the high-volume chemical and endocrine disruptor bisphenol A (BPA) and cardiovascular disorders, but there is a lack of experimental studies addressing the mechanisms of action of BPA on the cardiovascular system. In the present study, effects on markers for cardiovascular function of exposure to BPA and fructose in vivo in rat cardiac tissues, and of BPA exposure in human cardiomyocytes in vitro, were investigated.

    MATERIALS: Juvenile female Fischer 344 rats were exposed to 5, 50, and 500 μg BPA/kg bodyweight/day in their drinking water from 5 to 15 weeks of age, in combination with 5% fructose. Further, cultured human cardiomyocytes were exposed to 10 nM BPA to 1 × 10(4) nM BPA for six hours. Expression of markers for cardiovascular function and BPA target receptors was investigated using qRT-PCR.

    RESULTS: Exposure to 5 μg BPA/kg bodyweight/day plus fructose increased mRNA expression of Vegf, Vegfr2, eNos, and Ace1 in rat heart. Exposure of human cardiomyocytes to 1 × 10(4) nM BPA increased mRNA expression of eNOS and ACE1, as well as IL-8 and NFκβ known to regulate inflammatory response.

    CONCLUSIONS: . Low-dose exposure of juvenile rats to BPA and fructose induced up-regulation of expression of genes controlling angiogenesis and vascular tone in cardiac tissues. The observed effects of BPA in rat heart were in line with our present and previous studies of BPA in human endothelial cells and cardiomyocytes. These findings may aid in understanding the mechanisms of the association between BPA exposure and cardiovascular disorders reported in epidemiological studies.

  • 198. Knowles, Joshua W.
    et al.
    Xie, Weijia
    Zhang, Zhongyang
    Chennemsetty, Indumathi
    Assimes, Themistocles L.
    Paananen, Jussi
    Hansson, Ola
    Pankow, James
    Goodarzi, Mark O.
    Carcamo-Orive, Ivan
    Morris, Andrew P.
    Chen, Yii-Der I.
    Maekinen, Ville-Petteri
    Ganna, Andrea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mahajan, Anubha
    Guo, Xiuqing
    Abbasi, Fahim
    Greenawalt, Danielle M.
    Lum, Pek
    Molony, Cliona
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia
    Raffel, Leslie J.
    Tsao, Philip S.
    Schadt, Eric E.
    Rotter, Jerome I.
    Sinaiko, Alan
    Reaven, Gerald
    Yang, Xia
    Hsiung, Chao A.
    Groop, Leif
    Cordell, Heather J.
    Laakso, Markku
    Hao, Ke
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Frayling, Timothy M.
    Weedon, Michael N.
    Walker, Mark
    Quertermous, Thomas
    Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene2015Inngår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 125, nr 4, s. 1739-1751Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

  • 199.
    Kraja, Aldi T.
    et al.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostatist, Liverpool, Merseyside, England..
    Warren, Helen R.
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England..
    Surendran, Praveen
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.;Hebrew SeniorLife, Dept Med, Boston, MA USA..
    Grarup, Niels
    Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Drenos, Fotios
    Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England.;UCL, Ctr Cardiovasc Genet, Inst Cardiovasc Sci, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Smith, Albert Vernon
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England.;Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Blakemore, Alexandra I. F.
    Imperial Coll London, Sect Invest Med, Dept Med, London, England.;Brunel Univ, Dept Life Sci, London, England..
    Bork-Jensen, Jette
    Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Fava, Cristiano
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Univ Verona, Dept Med, Verona, Italy..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Herzig, Karl-Heinz
    Univ Oulu, Res Unit Biomed, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Med Res Ctr, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland.;Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland..
    Giri, Ayush
    Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN 37235 USA..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Grove, Megan L.
    McGovern Med Sch, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA.;Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Have, Christian T.
    Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Inst Mol Med Finland, Helsinki, Finland..
    Zhang, He
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Karajamaki, AnneMari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA..
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark..
    Little, Louis
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England..
    Liu, Yongmei
    Wake Forest Baptist Med Ctr, Epidemiol & Prevent Ctr Genom & Personalized Med, Med Ctr Blvd, Winston Salem, NC USA.;Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Ingram Canc Ctr,Vanderbilt Ep, Nashville, TN 37212 USA..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement, Sect Biol & Genet, Verona, Italy..
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Mei, Hao
    Univ Mississippi, Med Ctr, Dept Data Sci, Jackson, MS 39216 USA..
    Menni, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Morrison, Alanna C.
    McGovern Med Sch, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA.;Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA..
    Padmanabhan, Sandosh
    Univ Glasgow, British Heart Fdn, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci,Glasgow Cardiovasc Res Ct, Glasgow, Lanark, Scotland..
    Palmas, Walter
    Columbia Univ, Dept Med, Med Ctr, New York, NY USA..
    Poveda, Alaitz
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Rauramaa, Rainer
    Univ Eastern Finland, Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Rayner, Nigel William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.;Kuopio Univ Hosp, Kuopio, Finland..
    Riaz, Muhammad
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England..
    Rice, Ken
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Richard, Melissa A.
    McGovern Med Sch, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA.;McGovern Med Sch, Brown Fdn Inst Mol Med, Houston, TX 77030 USA..
    Smith, Jennifer A.
    Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Kuopio Univ Hosp, Kuopio, Finland..
    Stancakova, Alena
    Univ Eastern Finland, Kuopio, Finland..
    Stirrups, Kathleen E.
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;MRC BHF Cardiovasc Epidemiol Ctr, Dept Haematol, Cambridge, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Tuomi, Tiinamaija
    Helsinki Univ Cent Hosp, Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Cent Hosp, Dept Endocrinol, Helsinki, Finland.;Umea Univ, Dept Biobank Res, Umea, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Tzoulald, Ioanna
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece..
    Varga, Tibor V.
    Univ Eastern Finland, Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Weiss, Stefan
    Univ Med, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Berlin, Germany..
    Yiorkas, Andrianos M.
    Imperial Coll London, Sect Invest Med, Dept Med, London, England.;Brunel Univ, Dept Life Sci, London, England..
    Young, Robin
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, London, England..
    Barnes, Michael R.
    Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England..
    Cabrera, Claudia P.
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England..
    Gao, He
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boerwinkle, Eric
    McGovern Med Sch, Human Genet Ctr, Sch Publ Hlth, Houston, TX USA.;Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, London, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Connell, John M.
    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Christensen, Cramer K.
    Lillebaelt Hosp, Med Dept, Vejle, Denmark..
    de Boer, Rudolf A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Psychol, Edinburgh, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Deloukas, Panos
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England..
    Dominiczak, Anna F.
    Univ Glasgow, British Heart Fdn, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci,Glasgow Cardiovasc Res Ct, Glasgow, Lanark, Scotland..
    Dorr, Marcus
    Univ Med, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Med Infec, Greifswald, Germany..
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bldg 10, Bethesda, MD 20892 USA.;Hebrew SeniorLife, Inst Aging Res, Boston, MA USA..
    Edwards, Todd L.
    Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN 37235 USA..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Fornage, Myriam
    McGovern Med Sch, Brown Fdn Inst Mol Med, Houston, TX 77030 USA..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Gambaro, Giovanni
    Univ Cattolica Sacro Cuore, Dept Nephrol & Dialysis, Rome, Italy..
    Groop, Leif
    Lund Univ Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Hallmans, Goran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Hansen, Torben
    Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Heikki, Oksa
    Tampere Univ Hosp, Tampere, Finland..
    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, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.;Dasman Diabet Inst, Kuwait, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems An Der Donau, Austria..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland..
    Kardia, Sharon L. R.
    Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England..
    Lakka, Timo A.
    Univ Eastern Finland, Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Dept Clin Physiol & Nucl Med, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, 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..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Moris, Andrwe P.
    Univ Liverpool, Dept Biostatist, Liverpool, Merseyside, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland. Univ Split, Fac Med, Split, Croatia..
    Pedersen, Oluf
    Polasek, Ozren
    Poulter, Neil R.
    Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Province, Michael A.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA. Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA..
    Ridker, Paul M.
    Hebrew SeniorLife, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. Univ Edinburgh, Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Samani, Nilesh J.
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England..
    Sever, Peter J.
    Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Skaaby, Tea
    Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Stafford, Jeanette M.
    Starr, John M.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    van der Meer, Peter
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Vergnaud, Anne-Claire
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Willer, Cristen J.
    Univ Michigan, Dept Internal Med, Div Cardiovasc 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..
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.;Danish Diabet Acad, Odense, Denmark..
    Zeggini, Eleftheria
    Kuopio Univ Hosp, Kuopio, Finland..
    Saleheen, Danish
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Butterworth, Adam S.
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Cambridge Ctr Excellence, British Heart Fdn, Dept Med, Cambridge, England..
    Danesh, John
    MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England.;NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.;Univ Cambridge, Cambridge Ctr Excellence, British Heart Fdn, Dept Med, Cambridge, England.;Kuopio Univ Hosp, Kuopio, Finland..
    Asselbergs, Folkert W.
    UCL, Fac Populat Hlth Sci, London, England.;Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Wain, Louise V.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Ehret, Georg B.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.;Geneva Univ Hosp, Dept Med, Geneva, Switzerland..
    Chasman, Daniel I.
    Hebrew SeniorLife, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Caulfield, Mark J.
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Imperial Coll London, Natl Inst Hlth Res Imperial Coll Healthcare NHS T, Biomed Res Unit, London, England..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA..
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA..
    Newton-Cheh, Christopher
    Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA..
    Munroe, Patricia B.
    William Harvey Res Inst, Dept Clin Pharmacol, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England..
    Howson, Joanna M. M.
    Queen Mary Univ London, Natl Inst Hlth Res, Baits Cardiovasc Biomed Res Unit, London, England.;MRC BHF Cardiovasc Epidemiol Ctr, Dept Publ Hlth & Primary Care, Cambridge, England..
    New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals2017Inngår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, nr 5, artikkel-id e001778Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.

    Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.

    Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

  • 200.
    Kuhlmann, Antje
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Olafsdottir, Inga Sif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    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.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Association of biomarkers of inflammation and cell adhesion with lung function in the elderly: a population-based study2013Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 13, s. 82-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Low lung function is associated with increased morbidity and mortality. It is therefore of interest to identify biomarkers that are associated with impaired lung function. The aim of the study was to analyse associations of biomarkers and combinations of biomarkers with lung function in an elderly general population. Methods: Lung function (FEV1 and FVC) and a panel of 15 inflammatory markers from blood samples were analysed in 888 subjects aged 70 years. Biomarkers included cytokines, chemokines, adhesion molecules, C-reactive protein (CRP) and leukocyte count. Results: Leukocyte count and CRP were independently associated with FEV1 after adjustments for other inflammatory markers, sex, BMI, current smoking and pack-years of smoking. In a similar model, leukocyte count and vascular cell adhesion protein 1 (VCAM-1) were the biomarkers that were significantly associated with FVC. Subjects that had both leukocyte count and CRP in the lowest tertile had a FEV1 that was 9% of predicted higher than subjects with leukocyte count and CRP in the highest tertile (103 +/- 16 vs. 94 +/- 21% of predicted, p=0.0002) (mean +/- SD). A difference of 8% of predicted in FVC was found between subjects with leukocyte count and VCAM-1 in the lowest and highest tertiles, respectively (106 +/- 18 vs. 98 +/- 19% of predicted, p=0.002). Conclusion: Leucocyte count, CRP and VCAM-1 were found to relate to poorer lung function. A dose related association was found for the combination leukocyte count and CRP towards FEV1 and leukocyte and VCAM-1 towards FVC. This indicates that combination of two biomarkers yielded more information than assessing them one by one when analysing the association between systemic inflammation and lung function.

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