Biological, clinical and population relevance of 95 loci for blood lipids

Tanya M. Teslovich; Kiran Musunuru; Albert V. Smith; Andrew C. Edmondson; Ioannis M. Stylianou; Masahiro Koseki; James P. Pirruccello; Samuli Ripatti; Daniel I. Chasman; Cristen J. Willer; Christopher T. Johansen; Sigrid W. Fouchier; Aaron Isaacs; Gina M. Peloso; Maja Barbalic; Sally L. Ricketts; Joshua C. Bis; Yurii S. Aulchenko; Gudmar Thorleifsson; Mary F. Feitosa; John Chambers; Marju Orho-Melander; Olle Melander; Toby Johnson; Xiaohui Li; Xiuqing Guo; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C. Croteau-Chonka; Leslie A. Lange; Joshua D. Smith; Kijoung Song; Jing Hua Zhao; Xin Yuan; Jian'an Luan; Claudia Lamina; Andreas Ziegler; Weihua Zhang; Robert Y. L. Zee; Alan F. Wright; Jacqueline C. M. Witteman; James F. Wilson; Gonneke Willemsen; H. -Erich Wichmann; John B. Whitfield; Dawn M. Waterworth; Nicholas J. Wareham; Gerard Waeber; Peter Vollenweider; Benjamin F. Voight; Veronique Vitart; Andre G. Uitterlinden; Manuela Uda; Jaakko Tuomilehto; John R. Thompson; Toshiko Tanaka; Ida Surakka; Heather M. Stringham; Tim D. Spector; Nicole Soranzo; Johannes H. Smit; Juha Sinisalo; Kaisa Silander; Eric J. G. Sijbrands; Angelo Scuteri; James Scott; David Schlessinger; Serena Sanna; Veikko Salomaa; Juha Saharinen; Chiara Sabatti; Aimo Ruokonen; Igor Rudan; Lynda M. Rose; Robert Roberts; Mark Rieder; Bruce M. Psaty; Peter P. Pramstaller; Irene Pichler; Markus Perola; Brenda W. J. H. Penninx; Nancy L. Pedersen; Cristian Pattaro; Alex N. Parker; Guillaume Pare; Ben A. Oostra; Christopher J. O'Donnell; Markku S. Nieminen; Deborah A. Nickerson; Grant W. Montgomery; Thomas Meitinger; Ruth McPherson; Mark I. McCarthy; Wendy McArdle; David Masson; Nicholas G. Martin; Fabio Marroni; Massimo Mangino; Patrik K. E. Magnusson; Gavin Lucas; Robert Luben; Ruth J. F. Loos; Marja-Liisa Lokki; Guillaume Lettre; Claudia Langenberg; Lenore J. Launer; Edward G. Lakatta; Reijo Laaksonen; Kirsten O. Kyvik; Florian Kronenberg; Inke R. Koenig; Kay-Tee Khaw; Jaakko Kaprio; Lee M. Kaplan; Asa Johansson; Marjo-Riitta Jarvelin; A. Cecile J. W. Janssens; Erik Ingelsson; Wilmar Igi; G. Kees Hovingh; Jouke-Jan Hottenga; Albert Hofman; Andrew A. Hicks; Christian Hengstenberg; Iris M. Heid; Caroline Hayward; Aki S. Havulinna; Nicholas D. Hastie; Tamara B. Harris; Talin Haritunians; Alistair S. Hall; Ulf Gyllensten; Candace Guiducci; Leif C. Groop; Elena Gonzalez; Christian Gieger; Nelson B. Freimer; Luigi Ferrucci; Jeanette Erdmann; Paul Elliott; Kenechi G. Ejebe; Angela Doering; Anna F. Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Eco J. C. de Geus; Ulf de Faire; Gabriel Crawford; Francis S. Collins; Yii-der I. Chen; Mark J. Caulfield; Harry Campbell; Noel P. Burtt; Lori L. Bonnycastle; Dorret I. Boomsma; S. Matthijs Boekholdt; Richard N. Bergman; Ines Barroso; Stefania Bandinelli; Christie M. Ballantyne; Themistocles L. Assimes; Thomas Quertermous; David Altshuler; Mark Seielstad; Tien Y. Wong; E-Shyong Tai; Alan B. Feranil; Christopher W. Kuzawa; Linda S. Adair; Herman A. Taylor; Ingrid B. Borecki; Stacey B. Gabriel; James G. Wilson; Hilma Holm; Unnur Thorsteinsdottir; Vilmundur Gudnason; Ronald M. Krauss; Karen L. Mohlke; Jose M. Ordovas; Patricia B. Munroe; Jaspal S. Kooner; Alan R. Tall; Robert A. Hegele; John J. P. Kastelein; Eric E. Schadt; Jerome I. Rotter; Eric Boerwinkle; David P. Strachan; Vincent Mooser; Kari Stefansson; Muredach P. Reilly; Nilesh J. Samani; Heribert Schunkert; L. Adrienne Cupples; Manjinder S. Sandhu; Paul M. Ridker; Daniel J. Rader; Cornelia M. van Duijn; Leena Peltonen; Goncalo R. Abecasis; Michael Boehnke; Sekar Kathiresan

doi:10.1038/nature09270

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Biological, clinical and population relevance of 95 loci for blood lipids

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Biological, clinical and population relevance of 95 loci for blood lipids

Tanya M. Teslovich, Kiran Musunuru, Albert V. Smith, Andrew C. Edmondson, Ioannis M. Stylianou, Masahiro Koseki, James P. Pirruccello, Samuli Ripatti, Daniel I. Chasman, Cristen J. Willer, …

Nature (London), Vol.466(7307), pp.707-713

05/08/2010

DOI: https://doi.org/10.1038/nature09270

PMCID: PMC3039276

PMID: 20686565

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

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Title: Biological, clinical and population relevance of 95 loci for blood lipids
Creators - without role: Tanya M. Teslovich - University of Michigan–Ann Arbor
Kiran Musunuru - Center for Human Genetics
Albert V. Smith - University of Iceland
Andrew C. Edmondson - University of Pennsylvania
Ioannis M. Stylianou - Translational Therapeutics
Masahiro Koseki - Columbia University
James P. Pirruccello - Center for Human Genetics
Samuli Ripatti - Institute for Molecular Medicine Finland
Daniel I. Chasman - Brigham and Women's Hospital
Cristen J. Willer - Statistical Research
Christopher T. Johansen - Western University
Sigrid W. Fouchier - University of Amsterdam
Aaron Isaacs - Erasmus MC
Gina M. Peloso - Boston University
Maja Barbalic - The University of Texas Health Science Center at Houston
Sally L. Ricketts - University of Cambridge
Joshua C. Bis - University of Washington
Yurii S. Aulchenko - Erasmus MC
Gudmar Thorleifsson - deCODE Genetics
Mary F. Feitosa - Supreme Council Of Health
John Chambers - Imperial College London
Marju Orho-Melander - Lund University
Olle Melander - Lund University
Toby Johnson - Queen Mary University of London
Xiaohui Li - College Station Medical Center
Xiuqing Guo - Cedars-Sinai Medical Center
Mingyao Li - University of Pennsylvania
Yoon Shin Cho - Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea
Min Jin Go - Korea National Institute of Health
Young Jin Kim - Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea
Jong-Young Lee - Korea National Institute of Health
Taesung Park - Seoul National University
Kyunga Kim - Sookmyung Women's University
Xueling Sim - National University of Singapore
Rick Twee-Hee Ong - Genome Institute of Singapore
Damien C. Croteau-Chonka - University of North Carolina at Chapel Hill
Leslie A. Lange - University of North Carolina at Chapel Hill
Joshua D. Smith - University of Washington
Kijoung Song - GlaxoSmithKline
Jing Hua Zhao - MRC Epidemiology Unit
Xin Yuan - GlaxoSmithKline
Jian'an Luan - MRC Epidemiology Unit
Claudia Lamina - Innsbruck Medical University
Andreas Ziegler - University of Lübeck
Weihua Zhang - Imperial College London
Robert Y. L. Zee - Boston University
Alan F. Wright - MRC Institute of Genetics and Molecular Medicine
Jacqueline C. M. Witteman - Erasmus MC
James F. Wilson - University of Edinburgh
Gonneke Willemsen - Vrije Universiteit Amsterdam
H. -Erich Wichmann - Helmholtz Zentrum München
John B. Whitfield - QIMR Berghofer Medical Research Institute
Dawn M. Waterworth - GlaxoSmithKline
Nicholas J. Wareham - MRC Epidemiology Unit
Gerard Waeber - University Hospital of Lausanne
Peter Vollenweider - University Hospital of Lausanne
Benjamin F. Voight - Center for Human Genetics
Veronique Vitart - MRC Institute of Genetics and Molecular Medicine
Andre G. Uitterlinden - Erasmus MC
Manuela Uda - Institute of Genetic and Biomedical Research
Jaakko Tuomilehto - Finnish Institute for Health and Welfare
John R. Thompson - University of Leicester
Toshiko Tanaka - National Institutes of Health
Ida Surakka - University of Helsinki
Heather M. Stringham - University of Michigan–Ann Arbor
Tim D. Spector - King's College London
Nicole Soranzo - King's College London
Johannes H. Smit - University of Amsterdam
Juha Sinisalo - Helsinki University Hospital
Kaisa Silander - University of Helsinki
Eric J. G. Sijbrands - Erasmus MC
Angelo Scuteri - Istituto Nazionale di Riposo e Cura per Anziani
James Scott - Imperial College London
David Schlessinger - National Institute on Aging
Serena Sanna - Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy
Veikko Salomaa - Finnish Institute for Health and Welfare
Juha Saharinen - Institute for Molecular Medicine Finland
Chiara Sabatti - Stanford University
Aimo Ruokonen - University of Oulu
Igor Rudan - University of Edinburgh
Lynda M. Rose - Brigham and Women's Hospital
Robert Roberts - University of Ottawa
Mark Rieder - Seattle University
Bruce M. Psaty - Group Health Cooperative
Peter P. Pramstaller - University of Lübeck
Irene Pichler - Eurac Research
Markus Perola - University of Helsinki
Brenda W. J. H. Penninx - Amsterdam UMC Location VUmc
Nancy L. Pedersen - Karolinska Institutet
Cristian Pattaro - Eurac Research
Alex N. Parker - Amgen
Guillaume Pare - McMaster University
Ben A. Oostra - Erasmus MC
Christopher J. O'Donnell - Framingham Heart Study
Markku S. Nieminen - Helsinki University Hospital
Deborah A. Nickerson - University of Washington
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Thomas Meitinger - Technical University of Munich
Ruth McPherson - University of Ottawa
Mark I. McCarthy - Wellcome Centre for Human Genetics
Wendy McArdle - University of Bristol
David Masson - Columbia University
Nicholas G. Martin - College Station Medical Center
Fabio Marroni - Inst Appl Genom, I-33100 Udine, Italy
Massimo Mangino - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Patrik K. E. Magnusson - Karolinska Institutet
Gavin Lucas - College Station Medical Center
Robert Luben - University of Cambridge
Ruth J. F. Loos - Massachusetts Rehabilitation Commission
Marja-Liisa Lokki - University of Helsinki
Guillaume Lettre - Montreal Heart Institute
Claudia Langenberg - Massachusetts Rehabilitation Commission
Lenore J. Launer - NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA
Edward G. Lakatta - NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA
Reijo Laaksonen - Tampere University
Kirsten O. Kyvik - Univ So Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark
Florian Kronenberg - College Station Medical Center
Inke R. Koenig - University of Lübeck
Kay-Tee Khaw - University of Cambridge
Jaakko Kaprio - University of Helsinki
Lee M. Kaplan - Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA
Asa Johansson - Uppsala University
Marjo-Riitta Jarvelin - University of London
A. Cecile J. W. Janssens - College Station Medical Center
Erik Ingelsson - Karolinska Institutet
Wilmar Igi - Uppsala University
G. Kees Hovingh - University of Amsterdam
Jouke-Jan Hottenga - University of Amsterdam
Albert Hofman - College Station Medical Center
Andrew A. Hicks - University of Lübeck
Christian Hengstenberg - University of Regensburg
Iris M. Heid - Helmholtz Zentrum München
Caroline Hayward - College Station Medical Center
Aki S. Havulinna - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland
Nicholas D. Hastie - College Station Medical Center
Tamara B. Harris - NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA
Talin Haritunians - College Station Medical Center
Alistair S. Hall - University of Leeds
Ulf Gyllensten - Uppsala University
Candace Guiducci - Broad Institute
Leif C. Groop - Lund University
Elena Gonzalez - Broad Institute
Christian Gieger - Helmholtz Zentrum München
Nelson B. Freimer - Supreme Council Of Health
Luigi Ferrucci - NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA
Jeanette Erdmann - University of Lübeck
Paul Elliott - University of London
Kenechi G. Ejebe - Broad Institute
Angela Doering - Helmholtz Zentrum München
Anna F. Dominiczak - University of Glasgow
Serkalem Demissie - Boston University
Panagiotis Deloukas - Wellcome Sanger Institute
Eco J. C. de Geus - University of Amsterdam
Ulf de Faire - Karolinska Institutet
Gabriel Crawford - Broad Institute
Francis S. Collins - NHGRI, NIH, Bethesda, MD 20892 USA
Yii-der I. Chen - College Station Medical Center
Mark J. Caulfield - Queen Mary University of London
Harry Campbell - University of Edinburgh
Noel P. Burtt - Broad Institute
Lori L. Bonnycastle - NHGRI, NIH, Bethesda, MD 20892 USA
Dorret I. Boomsma - University of Amsterdam
S. Matthijs Boekholdt - University of Amsterdam
Richard N. Bergman - Biostat
Ines Barroso - Wellcome Sanger Institute
Stefania Bandinelli - Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
Christie M. Ballantyne - Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
Themistocles L. Assimes - Harvard University
Thomas Quertermous - Harvard University
David Altshuler - Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
Mark Seielstad - Genome Institute of Singapore
Tien Y. Wong - Broad Institute
E-Shyong Tai - Johns Hopkins University
Alan B. Feranil - Iceland Heart Assoc, Heart Prevent Clin & Res Inst, IS-201 Kopavogur, Iceland
Christopher W. Kuzawa - University of Iceland
Linda S. Adair - Supreme Council Of Health
Herman A. Taylor - University of Mississippi
Ingrid B. Borecki - Supreme Council Of Health
Stacey B. Gabriel - Broad Institute
James G. Wilson - University of Mississippi
Hilma Holm - DeCODE, IS-101 Reykjavik, Iceland
Unnur Thorsteinsdottir - University of Iceland
Vilmundur Gudnason - Iceland Heart Assoc, Heart Prevent Clin & Res Inst, IS-201 Kopavogur, Iceland
Ronald M. Krauss - Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
Jose M. Ordovas - Ctr Nacl Invest Cardiovasc, Dept Cardiovasc Epidemiol & Populat Genet, Madrid 28029, Spain
Patricia B. Munroe - Queen Mary University of London
Jaspal S. Kooner - University of London
Alan R. Tall - Columbia University
Robert A. Hegele - Western University
John J. P. Kastelein - University of Amsterdam
Eric E. Schadt - Sage Bionetworks
Jerome I. Rotter - College Station Medical Center
Eric Boerwinkle - Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA
David P. Strachan - University of London
Vincent Mooser - GlaxoSmithKline
Kari Stefansson - University of Iceland
Muredach P. Reilly - Supreme Council Of Health
Nilesh J. Samani - University of Leicester
Heribert Schunkert - University of Lübeck
L. Adrienne Cupples - Boston University
Manjinder S. Sandhu - University of Cambridge
Paul M. Ridker - Harvard University
Daniel J. Rader - Supreme Council Of Health
Cornelia M. van Duijn - College Station Medical Center
Leena Peltonen
Goncalo R. Abecasis - Biostat
Michael Boehnke - Biostat
Sekar Kathiresan - Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
Publication Details: Nature (London), Vol.466(7307), pp.707-713
Publisher: Springer Nature
Number of pages: 7
Grant note: ZIAAG000965 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) RR20649; U54 RR020278; M01-RR00425; UL1RR025005 / NCRR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) CA 047988 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32HL007208; 5R01HL08770003; K99 HL098364-01; RC2 HL102419; N01-HC-45133; N01-HC-25195; N02-HL-6-4278; N01-HC-85082; R01 HL087676; K99HL094535; N01-HC-55016; HL-54776; HL 080467; N01-HC-55022; N01-HC-85081; RC1 HL099634-02; R01HL086694; N01-HC-85086; 5R01HL087679-02; U01 HL080295; N01-HC-55021; N01-HC-85084; RC1 HL099634; RC2 HL101864,; R01HL087652; N01-HC-85079; K99 HL098364; RC1 HL099793; R01 HL089650; 5R01HL08821502; R01 HL089309; N01-HC-55018; U01 HL069757; N01 HC-15103; N01-HC-85080; R01HL59367; N01-HC-55020; N01-HC-75150; N01-HC-85083; HL 04381; N01-HC-55015; R01HL087641; N01-HC-85085; HL085144; N01-HC-55019; N01 HC-55222; N01-HC-35129 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01TW005596 / FOGARTY INTERNATIONAL CENTER; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC) U54RR020278 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) N01-AG-12100 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) ES10126 / NIEHS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) CZB/4/710 / Chief Scientist Office MC_qA137934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R24HD050924 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) N01-HG-65403; T32 HG000040; 1Z01 HG000024; U01HG004402; T32 HG00040 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) MC_U106188470; MC_U127561128; G9521010; G0801056; G0700931; MC_QA137934; G0000934; G0801566; G0401527; G9521010D; MC_U106179471; G0701863; G0601966 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R01HL064278 / 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) P30ES010126 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) PG/02/128; PG/08/094; SP/08/005/25115; RG/07/005/23633; PG/08/094/26019 / British Heart Foundation G0701863 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Intramural NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R24 HD050924 / NICHD NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) N01HC085083 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; 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Identifiers: 9935313608331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article