Common variants at 30 loci contribute to polygenic dyslipidemia

Sekar Kathiresan; Cristen J. Willer; Gina M. Peloso; Serkalem Demissie; Kiran Musunuru; Eric E. Schadt; Lee Kaplan; Derrick Bennett; Yun Li; Toshiko Tanaka; Benjamin F. Voight; Lori L. Bonnycastle; Anne U. Jackson; Gabriel Crawford; Aarti Surti; Candace Guiducci; Noel P. Burtt; Sarah Parish; Robert Clarke; Diana Zelenika; Kari A. Kubalanza; Mario A. Morken; Laura J. Scott; Heather M. Stringham; Pilar Galan; Amy J. Swift; Johanna Kuusisto; Richard N. Bergman; Jouko Sundvall; Markku Laakso; Luigi Ferrucci; Paul Scheet; Serena Sanna; Manuela Uda; Qiong Yang; Kathryn L. Lunetta; Josee Dupuis; Paul I. W. de Bakker; Christopher J. O'Donnell; John C. Chambers; Jaspal S. Kooner; Serge Hercberg; Pierre Meneton; Edward G. Lakatta; Angelo Scuteri; David Schlessinger; Jaakko Tuomilehto; Francis S. Collins; Leif Groop; David Altshuler; Rory Collins; G. Mark Lathrop; Olle Melander; Veikko Salomaa; Leena Peltonen; Marju Orho-Melander; Jose M. Ordovas; Michael Boehnke; Goncalo R. Abecasis; Karen L. Mohlke; L. Adrienne Cupples

doi:10.1038/ng.291

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Common variants at 30 loci contribute to polygenic dyslipidemia

Journal article

Peer reviewed

Common variants at 30 loci contribute to polygenic dyslipidemia

Sekar Kathiresan, Cristen J. Willer, Gina M. Peloso, Serkalem Demissie, Kiran Musunuru, Eric E. Schadt, Lee Kaplan, Derrick Bennett, Yun Li, Toshiko Tanaka, …

Nature genetics, Vol.41(1), pp.56-65

01/01/2009

DOI: https://doi.org/10.1038/ng.291

PMCID: PMC2881676

PMID: 19060906

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.

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Title: Common variants at 30 loci contribute to polygenic dyslipidemia
Creators - without role: Sekar Kathiresan - Framingham Heart Study
Cristen J. Willer - Statistical Research
Gina M. Peloso - Boston University
Serkalem Demissie - Boston University
Kiran Musunuru - Center for Human Genetics
Eric E. Schadt - Rosetta Stone
Lee Kaplan - Washington Center for Weight Management and Research
Derrick Bennett - University of Oxford
Yun Li - Statistical Research
Toshiko Tanaka - National Institutes of Health
Benjamin F. Voight - Broad Institute
Lori L. Bonnycastle - National Institutes of Health
Anne U. Jackson - University of Michigan–Ann Arbor
Gabriel Crawford - Broad Institute
Aarti Surti - Broad Institute
Candace Guiducci - Broad Institute
Noel P. Burtt - Broad Institute
Sarah Parish - University of Oxford
Robert Clarke - University of Oxford
Diana Zelenika - Atomic Energy and Alternative Energies Commission
Kari A. Kubalanza - National Human Genome Research Institute
Mario A. Morken - National Human Genome Research Institute
Laura J. Scott - University of Michigan–Ann Arbor
Heather M. Stringham - University of Michigan–Ann Arbor
Pilar Galan - Conservatoire National des Arts et Métiers
Amy J. Swift - National Human Genome Research Institute
Johanna Kuusisto - University of Eastern Finland
Richard N. Bergman - University of Southern California
Jouko Sundvall - Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland
Markku Laakso - University of Eastern Finland
Luigi Ferrucci - National Institute on Aging
Paul Scheet - Statistical Research
Serena Sanna - CNR, Ist Neurogenet & Neurofarmacol, I-08045 Cagliari, Italy
Manuela Uda - Institute of Genetic and Biomedical Research
Qiong Yang - Boston University
Kathryn L. Lunetta - Boston University
Josee Dupuis - National Heart Lung and Blood Institute
Paul I. W. de Bakker - Brigham and Women's Hospital
Christopher J. O'Donnell - National Heart Lung and Blood Institute
John C. Chambers - Imperial College London
Jaspal S. Kooner - Imperial College London
Serge Hercberg - Conservatoire National des Arts et Métiers
Pierre Meneton - Inserm
Edward G. Lakatta - National Institute on Aging
Angelo Scuteri - Istituto Nazionale di Riposo e Cura per Anziani
David Schlessinger - National Institute on Aging
Jaakko Tuomilehto - Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland
Francis S. Collins - National Institutes of Health
Leif Groop - Helsinki University Hospital
David Altshuler - Massachusetts General Hospital
Rory Collins - University of Oxford
G. Mark Lathrop - Atomic Energy and Alternative Energies Commission
Olle Melander - Lund University
Veikko Salomaa - Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, SF-00300 Helsinki, Finland
Leena Peltonen - Wellcome Sanger Institute
Marju Orho-Melander - Lund University
Jose M. Ordovas - Tufts University
Michael Boehnke - University of Michigan–Ann Arbor
Goncalo R. Abecasis - Statistical Research
Karen L. Mohlke - University of North Carolina at Chapel Hill
L. Adrienne Cupples - Boston University
Publication Details: Nature genetics, Vol.41(1), pp.56-65
Publisher: Springer Nature
Number of pages: 10
Grant note: R01 DK075030; R56 DK062370; P30 DK040561-13; R01 DK072193; R01 DK062370; U01 DK062370; P30 DK040561; DK062370; R01 DK029867; DK072193 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 089061 / Wellcome Trust; European Commission British Heart Foundation N01HG65403; HG02651; R01 HG002651 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01HG002651 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) U01DK062370 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) K23 HL083102-03; N01-HC-25195; K23 HL083102; N01HC25195; R01 HL054776; U01 HL084729; HL-54776; HL084729 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Cancer Research UK Department of Health; European Commission MC_U137686857 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission N01HC025195 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) MC_U137686857 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) K23HL083102 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) ZIAAG000799 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Z01 HG000024 / Intramural NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 53-K06-5-10 / PHS HHS; United States Department of Health & Human Services; United States Public Health Service
Identifiers: 9936183508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article