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  • 1.
    Bao, Xue
    et al.
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China;Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Muhammad, Iram Faqir
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Nilsson, Jan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Melander, Olle
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Niu, Kaijun
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor- superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population.

    Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.45.96years, 38.6% men) who were participants in the Malmo Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.05.16years (mean +/- SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP).

    Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p<0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n=3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged 55, 56-60 (>55 and 60) and >60years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p=0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061).

    Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are 60years old.

  • 2.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nilsson, Peter M.
    SUS Malmö, Dept Clin Sci, Malmö, Sweden.
    Elmståhl, Sölve
    Lund Univ, Malmö Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmö, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Physical activity may compensate for prolonged TV time regarding pulse rate-a cross-sectional study2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Background: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate.

    Methods: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time.

    Results: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1).

    Conclusions: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.

  • 3.
    Berglund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Length of time periods in treatment effect descriptions and willingness to initiate preventive therapy: a randomised survey experiment2018In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 18, article id 106Article in journal (Refereed)
    Abstract [en]

    Background Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. Methods In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n=1041, response rate 58.6%), the respondents, aged between 40 and 75years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event,DoE): 1month, 6months or 18months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. ResultsLonger DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18months, 6months and 1month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18months compared with a DoE of 1month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. ConclusionsLay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

  • 4.
    Bixby, Honor
    et al.
    Imperial College London, London, UK.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, Majid
    Imperial College London, London, UK.
    Rising rural body-mass index is the main driver of the global obesity epidemic in adults2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 569, no 7755, p. 260-264Article in journal (Other academic)
    Abstract [en]

    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

  • 5.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Elmstahl, S.
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Lund, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Both weight at age 20 and weight gain have an impact on sleep disturbances later in life – results of the epihealth study2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E195-E195Article in journal (Other academic)
  • 6.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    A framework for monitoring of new drugs in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

  • 7.
    Chróinín, Danielle Ní
    et al.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Asplund, Kjell
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Callaly, Elizabeth
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Cuadrado-Godia, Elisa
    Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain.
    Diez-Tejedor, Exuperio
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Di Napoli, Mario
    San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy; Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy .
    Engelter, Stefan T.
    Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
    Furie, Karen L.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Giannopoulos, Sotirios
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Gotto, Antonio M., Jr.
    Weill Cornell Med Coll, New York, NY USA.
    Hannon, Niamh
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Jonsson, Fredrik
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Kapral, Moira K.
    Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada.
    Martí-Fàbregas, Joan
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Martínez-Sánchez, Patricia
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Milionis, Haralampos J.
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Montaner, Joan
    Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain; Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain.
    Muscari, Antonio
    Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy.
    Pikija, Slaven
    Gen Hosp Varazdin, Varazhdin, Croatia.
    Probstfield, Jeffrey
    Univ Washington, Dept Med, Seattle, WA USA; Univ Washington, Dept Epidemiol, Seattle, WA USA.
    Rost, Natalia S.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Thrift, Amanda G.
    Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia; Natl Stroke Res Inst, Heidelberg, Vic, Australia.
    Vemmos, Konstantinos
    Univ Athens, Dept Therapeut, Alexandra Hosp, Athens, Greece.
    Kelly, Peter J.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 2, p. 448-456Article, review/survey (Refereed)
    Abstract [en]

    Background and Purpose: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke.

    Methods: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients.

    Results: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients).

    Conclusion: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  • 8.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 9.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Faculty of Pharmacy, Medical University of Gdansk, Poland.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Forsberg, Lars A.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Beijer Laboratory of Genome Research, Uppsala University.
    Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events2017In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, no 4Article in journal (Other academic)
  • 10.
    Feo, Rebecca
    et al.
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia;Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia.
    Donnelly, Frank
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Jangland, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Providing high-quality fundamental care for patients with acute abdominal pain: A qualitative study of patients' experiences in acute care2019In: Journal of Health Organisation & Management, ISSN 1477-7266, E-ISSN 1758-7247, Vol. 33, no 1, p. 110-123Article in journal (Refereed)
    Abstract [en]

    Purpose Globally, acute abdominal pain (AAP) is one of the most common reasons for emergency admissions, yet little is known about how this patient group experiences the delivery of fundamental care across the acute care delivery chain. The purpose of this paper is to describe how patients with AAP experienced fundamental care across their acute care presentation, and to explicate the health professional behaviours, reported by patients, that contributed to their positive experiences. Design/methodology/approach A qualitative descriptive study, using repeated reflective interviews, was analysed thematically (n=10 patients). Findings Two themes were identified: developing genuine, caring relationships with health professionals and being informed about one's care. Patients reported that health professionals established genuine professional-patient relationships despite the busy care environment but perceived this environment as impeding information-provision. Patients were typically accepting of a lack of information, whereas poor professional-patient relationships were seen as inexcusable.

  • 11.
    Franceschini, Nora
    et al.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Giambartolomei, Claudia
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
    de Vries, Paul S.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Huntley, Rachael P.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Lovering, Ruth C.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
    Graff, Misa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Dale, Caroline
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria;Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
    van Leeuwen, Elisabeth M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Lu, Lingyi
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Pitkanen, Niina
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland.
    Franzen, Oscar
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands.
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Framingham, MA 01702 USA;NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA.
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, D-17475 Greifswald, Germany.
    Palmas, Walter
    Columbia Univ, Dept Med, New York, NY 10032 USA.
    Isaacs, Aaron
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Maastricht Univ, CARIM Sch Cardiovasc Dis, Maastricht Ctr Syst Biol MaCSBio, Dept Biochem, NL-6229 Maastricht, Netherlands.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 25157 USA;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld 4222, Australia.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Smit, Andries J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-2300 Groningen, Netherlands.
    Newman, Anne B.
    Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA;Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
    Britton, Annie
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Ruusalepp, Arno
    Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, EE-51010 Tartu, Estonia.
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Hedblad, Bo
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Pasaniuc, Bogdan
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA;Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
    Penninx, Brenda W.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci Campus Amste, Department Psychiat, NL-1081 HL Amsterdam, Netherlands.
    Langefeld, Carl D.
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Wassel, Christina L.
    Premier Inc, Appl Sci, Charlotte, NC 28277 USA.
    Tzourio, Christophe
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Fava, Cristiano
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden;Univ Verona, Dept Med, I-37134 Verona, Italy.
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, I-20133 Milan, Italy;IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    O'Leary, Daniel H.
    Tufts Univ, Sch Med, St Elizabeths Med Ctr, Boston, MA 02135 USA.
    Teupser, Daniel
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Kuh, Diana
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Tremoli, Elena
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy;Univ Milan, Dipartimento Sci Farmacol Biomol, I-20133 Milan, Italy.
    Mannarino, Elmo
    Univ Perugia, Internal Med Angiol & Arteriosclerosis Dis, Dept Clin & Expt Med, I-06123 Perugia, Italy.
    Grossi, Enzo
    Ctr Diagnost Italiano, I-20147 Milan, Italy.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94309 USA;Stanford Univ, Stanford Cardiovasc Inst, G1120, Stanford, CA USA.
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Beutner, Frank
    Heart Ctr Leipzig, D-04103 Leipzig, Germany.
    Chauhan, Ganesh
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France;Indian Inst Sci, Ctr Brain Res, Bangalore 560012, Karnataka, India.
    Heiss, Gerardo
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Markus, Hugh S.
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands.
    Price, Jacqueline
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Pott, Janne
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Liang, Jingjing
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany.
    Engmann, Jorgen
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
    Taylor, Kent D.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Dhana, Klodian
    Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27516 USA.
    Launer, Lenore J.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Holdt, Lesca M.
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Doer, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, D-17475 Greifswald, Germany.
    Dichgans, Martin
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany;Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.
    Traylor, Matthew
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Sitzer, Matthias
    Goethe Univ Frankfurt, Ctr Neurol & Neurosurg, Dept Neurol, D-60323 Frankfurt, Germany.
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;Essex Univ, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Bern, ISPM, CH-3012 Bern, Switzerland.
    Rueda-Ochoa, Oscar L.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Ind Santander, Sch Med, Electrocardiog Res Grp, Santander 680003, Colombia.
    Roussos, Panos
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA;James J Peters VA Med Ctr, MIRECC, Bronx, NY 10468 USA.
    Whincup, Peter H.
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.
    Amouyel, Philippe
    INSERM, U1167, F-59000 Lille, France;Inst Pasteur, U1167, F-59000 Lille, France;Univ Lille, U1167, RID AGE, F-59000 Lille, France;CHU Lille, U1167, F-59000 Lille, France.
    Giral, Philippe
    Sorbonne Univ, Pitie Salpetriere Hosp, Cardiovasc Prevent Unit, F-75013 Paris, France.
    Anugu, Pramod
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Wong, Quenna
    Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
    Malik, Rainer
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, D-93053 Regensburg, Germany.
    Hardy, Rebecca
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands.
    Morris, Richard W.
    Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol BS8 1QU, Avon, England.
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden;Univ Glasgow, Inst Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow G12 0XH, Lanark, Scotland.
    Wannamethee, S. Goya
    UCL, Dept Primary Care & Populat Hlth, London WC1E 6BT, England.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
    Shah, Sonia
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    McLachlan, Stela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, FI-70210 Kuopio, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA.
    Ring, Susan
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Shah, Tina
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, S-17177 Stockholm, Sweden.
    Plagnol, Vincent
    UCL, Genet Inst, London WC1E 6BT, England.
    Rosamond, Wayne D.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Post, Wendy
    Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
    Zhu, Xiaofeng
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Zhang, Xiaoling
    NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA;Boston Univ, Sch Med, Sect Biomed Genet, Boston, MA 02215 USA.
    Guo, Xiuqing
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London SW7 2AZ, England.
    Seldenrijk, Adrie
    Univ Amsterdam, Med Ctr, Dept Psychiat, GGZ inGeest & Amsterdam Publ Hlth Res Inst, NL-1081 HV Amsterdam, Netherlands.
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Psaty, Bruce M.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA;Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Lawlor, Deborah A.
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands.
    Bowden, Donald W.
    Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Gen, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Wardlaw, Joanna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland;Univ Edinburgh, UK Dementia Res Inst, Edinburgh EH16 4SB, Midlothian, Scotland.
    Deanfield, John
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Halcox, Julian
    Swansea Univ, Med Sch, Swansea SA2 8PP, W Glam, Wales.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Debette, Stephanie
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Crt Cardiovasc Genet, London WC1E 6BT, England.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Gen, D-17475 Greifswald, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bjorkegren, Johan L. M.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Karolinska Univ Sjukhuset, Karolinska Inst, Dept Med, Integrated Cardio Metab Ctr, SE-14157 Huddinge, Sweden.
    Casas, Juan P.
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    O'Donnell, Christopher J.
    NHLBI, Intramural Adm Management Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02130 USA;Harvard Med Sch, Boston, MA 02115 USA.
    GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 5141Article in journal (Refereed)
    Abstract [en]

    Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

  • 12.
    Fresard, Laure
    et al.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Smail, Craig
    Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA.
    Ferraro, Nicole M.
    Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA.
    Teran, Nicole A.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Li, Xin
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Smith, Kevin S.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bonner, Devon
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kernohan, Kristin D.
    Childrens Hosp Eastern Ontario, NSO, Ottawa, ON, Canada.
    Marwaha, Shruti
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zappala, Zachary
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Balliu, Brunilda
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
    Davis, Joe R.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Liu, Boxiang
    Stanford Univ, Sch Humanities & Sci, Dept Biol, Stanford, CA 94305 USA.
    Prybol, Cameron J.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Kohler, Jennefer N.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zastrow, Diane B.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Reuter, Chloe M.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fisk, Dianna G.
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Grove, Megan E.
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Davidson, Jean M.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hartley, Taila
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Joshi, Ruchi
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Strober, Benjamin J.
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
    Utiramerur, Sowmithri
    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ingelsson, Erik
    Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Battle, Alexis
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA;Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
    Bejerano, Gill
    Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA.
    Bernstein, Jonathan A.
    Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ashley, Euan A.
    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA;Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boycott, Kym M.
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Merker, Jason D.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27515 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wheeler, Matthew T.
    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Montgomery, Stephen B.
    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
    Adams, David R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Aday, Aaron
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Alejandro, Mercedes E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Allard, Patrick
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Azamian, Mahshid S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bacino, Carlos A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Baker, Eva
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Balasubramanyam, Ashok
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Barseghyan, Hayk
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Batzli, Gabriel F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Beggs, Alan H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Behnam, Babak
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bellen, Hugo J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Berry, Gerard T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bican, Anna
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bick, David P.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Birch, Camille L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boone, Braden E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Bostwick, Bret L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Briere, Lauren C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brokamp, Elly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brown, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Brush, Matthew
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Burke, Elizabeth A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Burrage, Lindsay C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Butte, Manish J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Chen, Shan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Clark, Gary D.
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    Coakley, Terra R.
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    Cogan, Joy D.
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    Colley, Heather A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Cooper, Cynthia M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Cope, Heidi
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Craigen, William J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    D'Souza, Precilla
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Davids, Mariska
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dayal, Jyoti G.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dell'Angelica, Esteban C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dhar, Shweta U.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dipple, Katrina M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Donnell-Fink, Laurel A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dorrani, Naghmeh
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dorset, Daniel C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Douine, Emilie D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Draper, David D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Dries, Annika M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Duncan, Laura
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eckstein, David J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Emrick, Lisa T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eng, Christine M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Enns, Gregory M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Eskin, Ascia
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Esteves, Cecilia
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Estwick, Tyra
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fernandez, Liliana
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ferreira, Carlos
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fieg, Elizabeth L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fisher, Paul G.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Fogel, Brent L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Friedman, Noah D.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gahl, William A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Glanton, Emily
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Godfrey, Rena A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Goldman, Alica M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Goldstein, David B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gould, Sarah E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gourdine, Jean-Philippe F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Groden, Catherine A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Gropman, Andrea L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Haendel, Melissa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hamid, Rizwan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hanchard, Neil A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    High, Frances
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Holm, Ingrid A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Hom, Jason
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Howerton, Ellen M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Huang, Yong
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jamal, Fariha
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jiang, Yong-hui
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Johnston, Jean M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Jones, Angela L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Karaviti, Lefkothea
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Koeller, David M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kohane, Isaac S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Krasnewich, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Korrick, Susan
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Koziura, Mary
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Krier, Joel B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Kyle, Jennifer E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lalani, Seema R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lau, C. Christopher
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lazar, Jozef
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    LeBlanc, Kimberly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Brendan H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Hane
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Levy, Shawn E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lewis, Richard A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Lincoln, Sharyn A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Loo, Sandra K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Loscalzo, Joseph
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Maas, Richard L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Macnamara, Ellen F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    MacRae, Calum A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Maduro, Valerie V.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Majcherska, Marta M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Malicdan, May Christine V.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Mamounas, Laura A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Manolio, Teri A.
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    Markello, Thomas C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Marom, Ronit
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Martin, G. Martin
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Martinez-Agosto, Julian A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    May, Thomas
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McConkie-Rosell, Allyn
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McCormack, Colleen E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    McCray, Alexa T.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Metz, Thomas O.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Might, Matthew
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Moretti, Paolo M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Morimoto, Marie
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Mulvihill, John J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Murdock, David R.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Murphy, Jennifer L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Muzny, Donna M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Nehrebecky, Michele E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Nelson, Stan F.
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    Newberry, J. Scott
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    Newman, John H.
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    Nicholas, Sarah K.
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    Novacic, Donna
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    Orange, Jordan S.
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    Orengo, James P.
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    Pallais, J. Carl
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    Palmer, Christina G. S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Papp, Jeanette C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Parker, Neil H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Pena, Loren D. M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Phillips, John A., III
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    Posey, Jennifer E.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Postlethwait, John H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Potocki, Lorraine
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Pusey, Barbara N.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Renteria, Genecee
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rives, Lynette
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Robertson, Amy K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rodan, Lance H.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Rosenfeld, Jill A.
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    Sampson, Jacinda B.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Samson, Susan L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Schoch, Kelly
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Scott, Daryl A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Shakachite, Lisa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sharma, Prashant
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Shashi, Vandana
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Signer, Rebecca
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Silverman, Edwin K.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sinsheimer, Janet S.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Spillmann, Rebecca C.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Stoler, Joan M.
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    Stong, Nicholas
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    Sullivan, Jennifer A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Sweetser, David A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Tan, Queenie K. -G.
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    Tifft, Cynthia J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Toro, Camilo
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Tran, Alyssa A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Urv, Tiina K.
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    Vilain, Eric
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Vogel, Tiphanie P.
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    Waggott, Daryl M.
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    Wahl, Colleen E.
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    Walley, Nicole M.
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    Walsh, Chris A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Walker, Melissa
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wan, Jijun
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    Wangler, Michael F.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Ward, Patricia A.
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    Waters, Katrina M.
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    Webb-Robertson, Bobbie-Jo M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Westerfield, Monte
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wise, Anastasia L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wolfe, Lynne A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Worthey, Elizabeth A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yamamoto, Shinya
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, John
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, Yaping
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yoon, Amanda J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yu, Guoyun
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zhao, Chunli
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zheng, Allison
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boycott, Kym
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    MacKenzie, Alex
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Majewski, Jacek
    McGill Univ, Montreal, PQ, Canada.
    Brudno, Michael
    Univ Toronto, Toronto, ON, Canada.
    Bulman, Dennis
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Dyment, David
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts2019In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 6, p. 911-919Article in journal (Refereed)
    Abstract [en]

    It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.

  • 13.
    Henriksson, Peter
    et al.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    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 flow2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 5, p. 322-326Article in journal (Refereed)
    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.

  • 14.
    Jangland, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Teodorsson, Therese
    Hoglandssjukhuset Eksjo, Dept Surg, Eksjo, Sweden.
    Molander, Karin
    Sundsvall Hosp, Dept Surg, Sundsvall, Sweden.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Inadequate environment, resources, and values lead to missed nursing care: A focused ethnographic study on the surgical ward using the Fundamentals of Care framework2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 11-12, p. 2311-2321Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: The purpose was to explore the delivery of care from the perspective of patients with acute abdominal pain focusing on the contextual factors at system level using the Fundamentals of Care framework.

    BACKGROUND: The Fundamentals of Care framework describes several contextual and systemic factors that can impact the delivery of care. To deliver high- quality, person-centred care it is important to understand how these factors affect patients' experiences and care needs.

    DESIGN: A focused ethnographic approach.

    METHOD: A total of 20 observations were performed on two surgical wards at a Swedish university hospital. Data were collected using participant observation and informal interviews and analysed using deductive content analysis.

    RESULTS: The findings, presented in four categories, reflect the value patients place on the caring relationship and a friendly atmosphere on the ward. Patients had concerns about the environment, particularly the high-tempo culture on the ward and its impact on their integrity, rest and sleep, access to information and planning, and need for support in addressing their existential thoughts. The observers also noted that missed nursing care had serious consequences for patient safety.

    CONCLUSION: Patients with acute abdominal pain were cared for in the high-tempo culture of a surgical ward with limited resources, unclear leadership, and challenges to patients' safety. The findings highlight the crucial importance of prioritizing and valuing the patients' fundamental care needs for recovery.

    RELEVANCE TO CLINICAL PRACTICE: Nursing leaders and nurses need to take the lead to re-conceptualize the value of fundamental care in the acute care setting. To improve clinical practice the value of fundamentals of care must be addressed regardless of patient's clinical condition. Providing a caring relationship is paramount to ensure a positive impact on patient's well-being and recovery.

  • 15. Justice, Anne E.
    et al.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindgren, Cecilia M.
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 452-469Article in journal (Refereed)
    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.

  • 16.
    Kaptoge, Stephen
    et al.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Di Angelantonio, Emanuele
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions2019In: The Lancet Global Health, E-ISSN 2214-109X, Vol. 7, no 10, p. E1332-E1345Article in journal (Refereed)
    Abstract [en]

    Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.

    Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.

    Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.

    Interpretation: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.

    Funding: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.

  • 17.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. 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 mass2019In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 276-287Article in journal (Refereed)
    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.

  • 18.
    Larsson, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden.
    Farahmand, Bahman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Zelano, J.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden.
    Risk of Stroke after Late-Onset Seizures: A Swedish Register-Based Case-Control Study2018In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 59, p. S5-S6Article in journal (Other academic)
  • 19.
    Larsson, David
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden; Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden; Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study2019In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 64, p. 29-33Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale.

    Methods: The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005–2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014.

    Results: A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4–79.4), followed by levetiracetam (69%, 95%CI:62.9–74.3), oxcarbazepine (68%, 95%CI:55.2–79.8), valproic acid (62%, 95%CI:57.8–66.4), carbamazepine (60%, 95%CI:57.6–62.4), and phenytoin (55%, 95%CI:45.2–64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine.

    Conclusions: Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group.

  • 20.
    Laszkowska, M.
    et al.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Mahadev, S.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lebwohl, B.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Green, P. H. R.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, J. F.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.
    Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 6, p. 590-597Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis.

    AIMS: To investigate the prevalence of CD among individuals with osteoporosis.

    METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression.

    RESULTS:  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%).

    CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

  • 21. Ligthart, Symen
    et al.
    Vaez, Ahmad
    Võsa, Urmo
    Stathopoulou, Maria G
    de Vries, Paul S
    Prins, Bram P
    Van der Most, Peter J
    Tanaka, Toshiko
    Naderi, Elnaz
    Rose, Lynda M
    Wu, Ying
    Karlsson, Robert
    Barbalic, Maja
    Lin, Honghuang
    Pool, René
    Zhu, Gu
    Macé, Aurélien
    Sidore, Carlo
    Trompet, Stella
    Mangino, Massimo
    Sabater-Lleal, Maria
    Kemp, John P
    Abbasi, Ali
    Kacprowski, Tim
    Verweij, Niek
    Smith, Albert V
    Huang, Tao
    Marzi, Carola
    Feitosa, Mary F
    Lohman, Kurt K
    Kleber, Marcus E
    Milaneschi, Yuri
    Mueller, Christian
    Huq, Mahmudul
    Vlachopoulou, Efthymia
    Lyytikäinen, Leo-Pekka
    Oldmeadow, Christopher
    Deelen, Joris
    Perola, Markus
    Zhao, Jing Hua
    Feenstra, Bjarke
    Amini, Marzyeh
    Lahti, Jari
    Schraut, Katharina E
    Fornage, Myriam
    Suktitipat, Bhoom
    Chen, Wei-Min
    Li, Xiaohui
    Nutile, Teresa
    Malerba, Giovanni
    Luan, Jian'an
    Bak, Tom
    Schork, Nicholas
    Del Greco M, Fabiola
    Thiering, Elisabeth
    Mahajan, Anubha
    Marioni, Riccardo E
    Mihailov, Evelin
    Eriksson, Joel
    Ozel, Ayse Bilge
    Zhang, Weihua
    Nethander, Maria
    Cheng, Yu-Ching
    Aslibekyan, Stella
    Ang, Wei
    Gandin, Ilaria
    Yengo, Loïc
    Portas, Laura
    Kooperberg, Charles
    Hofer, Edith
    Rajan, Kumar B
    Schurmann, Claudia
    den Hollander, Wouter
    Ahluwalia, Tarunveer S
    Zhao, Jing
    Draisma, Harmen H M
    Ford, Ian
    Timpson, Nicholas
    Teumer, Alexander
    Huang, Hongyan
    Wahl, Simone
    Liu, YongMei
    Huang, Jie
    Uh, Hae-Won
    Geller, Frank
    Joshi, Peter K
    Yanek, Lisa R
    Trabetti, Elisabetta
    Lehne, Benjamin
    Vozzi, Diego
    Verbanck, Marie
    Biino, Ginevra
    Saba, Yasaman
    Meulenbelt, Ingrid
    O'Connell, Jeff R
    Laakso, Markku
    Giulianini, Franco
    Magnusson, Patrik K E
    Ballantyne, Christie M
    Hottenga, Jouke Jan
    Montgomery, Grant W
    Rivadineira, Fernando
    Rueedi, Rico
    Steri, Maristella
    Herzig, Karl-Heinz
    Stott, David J
    Menni, Cristina
    Frånberg, Mattias
    St Pourcain, Beate
    Felix, Stephan B
    Pers, Tune H
    Bakker, Stephan J L
    Kraft, Peter
    Peters, Annette
    Vaidya, Dhananjay
    Delgado, Graciela
    Smit, Johannes H
    Großmann, Vera
    Sinisalo, Juha
    Seppälä, Ilkka
    Williams, Stephen R
    Holliday, Elizabeth G
    Moed, Matthijs
    Langenberg, Claudia
    Räikkönen, Katri
    Ding, Jingzhong
    Campbell, Harry
    Sale, Michele M
    Chen, Yii-Der I
    James, Alan L
    Ruggiero, Daniela
    Soranzo, Nicole
    Hartman, Catharina A
    Smith, Erin N
    Berenson, Gerald S
    Fuchsberger, Christian
    Hernandez, Dena
    Tiesler, Carla M T
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Liewald, David
    Fischer, Krista
    Mellström, Dan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wang, Yunmei
    Scott, William R
    Lorentzon, Matthias
    Beilby, John
    Ryan, Kathleen A
    Pennell, Craig E
    Vuckovic, Dragana
    Balkau, Beverly
    Concas, Maria Pina
    Schmidt, Reinhold
    Mendes de Leon, Carlos F
    Bottinger, Erwin P
    Kloppenburg, Margreet
    Paternoster, Lavinia
    Boehnke, Michael
    Musk, A W
    Willemsen, Gonneke
    Evans, David M
    Madden, Pamela A F
    Kähönen, Mika
    Kutalik, Zoltán
    Zoledziewska, Magdalena
    Karhunen, Ville
    Kritchevsky, Stephen B
    Sattar, Naveed
    Lachance, Genevieve
    Clarke, Robert
    Harris, Tamara B
    Raitakari, Olli T
    Attia, John R
    van Heemst, Diana
    Kajantie, Eero
    Sorice, Rossella
    Gambaro, Giovanni
    Scott, Robert A
    Hicks, Andrew A
    Ferrucci, Luigi
    Standl, Marie
    Lindgren, Cecilia M
    Starr, John M
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Li, Jun Z
    Chambers, John C
    Mori, Trevor A
    de Geus, Eco J C N
    Heath, Andrew C
    Martin, Nicholas G
    Auvinen, Juha
    Buckley, Brendan M
    de Craen, Anton J M
    Waldenberger, Melanie
    Strauch, Konstantin
    Meitinger, Thomas
    Scott, Rodney J
    McEvoy, Mark
    Beekman, Marian
    Bombieri, Cristina
    Ridker, Paul M
    Mohlke, Karen L
    Pedersen, Nancy L
    Morrison, Alanna C
    Boomsma, Dorret I
    Whitfield, John B
    Strachan, David P
    Hofman, Albert
    Vollenweider, Peter
    Cucca, Francesco
    Jarvelin, Marjo-Riitta
    Jukema, J Wouter
    Spector, Tim D
    Hamsten, Anders
    Zeller, Tanja
    Uitterlinden, André G
    Nauck, Matthias
    Gudnason, Vilmundur
    Qi, Lu
    Grallert, Harald
    Borecki, Ingrid B
    Rotter, Jerome I
    März, Winfried
    Wild, Philipp S
    Lokki, Marja-Liisa
    Boyle, Michael
    Salomaa, Veikko
    Melbye, Mads
    Eriksson, Johan G
    Wilson, James F
    Penninx, Brenda W J H
    Becker, Diane M
    Worrall, Bradford B
    Gibson, Greg
    Krauss, Ronald M
    Ciullo, Marina
    Zaza, Gianluigi
    Wareham, Nicholas J
    Oldehinkel, Albertine J
    Palmer, Lyle J
    Murray, Sarah S
    Pramstaller, Peter P
    Bandinelli, Stefania
    Heinrich, Joachim
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA.
    Deary, Ian J
    Mägi, Reedik
    Vandenput, Liesbeth
    van der Harst, Pim
    Desch, Karl C
    Kooner, Jaspal S
    Ohlsson, Claes
    Hayward, Caroline
    Lehtimäki, Terho
    Shuldiner, Alan R
    Arnett, Donna K
    Beilin, Lawrence J
    Robino, Antonietta
    Froguel, Philippe
    Pirastu, Mario
    Jess, Tine
    Koenig, Wolfgang
    Loos, Ruth J F
    Evans, Denis A
    Schmidt, Helena
    Smith, George Davey
    Slagboom, P Eline
    Eiriksdottir, Gudny
    Morris, Andrew P
    Psaty, Bruce M
    Tracy, Russell P
    Nolte, Ilja M
    Boerwinkle, Eric
    Visvikis-Siest, Sophie
    Reiner, Alex P
    Gross, Myron
    Bis, Joshua C
    Franke, Lude
    Franco, Oscar H
    Benjamin, Emelia J
    Chasman, Daniel I
    Dupuis, Josée
    Snieder, Harold
    Dehghan, Abbas
    Alizadeh, Behrooz Z
    Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders2018In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, no 5, p. 691-706, article id S0002-9297(18)30320-3Article in journal (Refereed)
    Abstract [en]

    C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

  • 22.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Population-based cardiovascular cohort studies in Uppsala2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 16-20Article in journal (Refereed)
    Abstract [en]

    The first population-based cohort study in Uppsala with the aim to study cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle-aged men has since then been followed in a longitudinal fashion for almost 50 years. This study has been followed by the PIVUS study, investigating 1000 men and women at ages 70, 75, and 80. A very detailed examination has also been performed in 500 subjects aged 50 years, the POEM study. In recent years, a high-throughput study conducted in 13000 subjects has also been performed, named EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS study. Taken together, these cardiovascular-oriented studies constitute a very rich source for cardiovascular epidemiological research in Uppsala. This review summarizes the design of these studies and highlights some of the important results published based on data from these studies.

  • 23.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Geriatr Med, Malmo, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Cardiometabolic Proteins Associated with Metabolic Syndrome2019In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518Article in journal (Refereed)
    Abstract [en]

    Background: Although metabolic syndrome (MetS) was described in the late 80s, the molecular mechanisms underlying clustering of risk factors in certain individuals are not fully understood. The present study used targeted proteomics to establish cardiometabolic proteins related to all MetS components, thereby providing new hypotheses regarding pathways involved in the pathogenesis of MetS.

    Methods: In the EpiHealth study, 249 cardiometabolic proteins were measured by proximity extension assay (PEA) and related to the five MetS components [consensus-modified National Cholesterol Education Program (NCEP) criteria] in 2,444 participants aged 45-75 years (50% women).

    Results: Thirty-one proteins were associated with systolic blood pressure following adjustment for age and sex (P < 0.000040, taking multiple testing into account). The corresponding number of proteins significantly associated with fasting glucose, waist circumference, high-density lipoprotein cholesterol, and serum triglycerides were 58, 132, 127, and 148. Twenty-two proteins were significantly related to all 5 MetS components, and of those, 20 were with MetS as a binary outcome (n = 600, 24% of the sample) following adjustment for age, sex, fat mass, and lifestyle factors (alcohol intake, smoking, education, and exercise habits).

    Conclusion: Using targeted proteomics, we identified 20 proteins reflecting a range of pathways, such as immunomodulation at different levels; regulation of adipocyte differentiation; lipid, carbohydrate, and amino acid metabolism; or insulin-like growth factor signaling, to be strongly associated with MetS independently of fat mass and lifestyle factors. Whether some of these proteins are causally involved in the pathogenesis of clustering of multiple risk factors in the same individual remains to be investigated.

  • 24.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala