Discovery and refinement of loci associated with lipid levels

Cristen J Willer; Ellen M Schmidt; Sebanti Sengupta; Gina M Peloso; Stefan Gustafsson; Stavroula Kanoni; Andrea Ganna; Jin Chen; Martin L Buchkovich; Samia Mora; Jacques S Beckmann; Jennifer L Bragg-Gresham; Hsing-Yi Chang; Ayşe Demirkan; Heleen M Den Hertog; Ron Do; Louise A Donnelly; Georg B Ehret; Tõnu Esko; Mary F Feitosa; Teresa Ferreira; Krista Fischer; Pierre Fontanillas; Ross M Fraser; Daniel F Freitag; Deepti Gurdasani; Kauko Heikkilä; Elina Hyppönen; Aaron Isaacs; Anne U Jackson; Åsa Johansson; Toby Johnson; Marika Kaakinen; Johannes Kettunen; Marcus E Kleber; Xiaohui Li; Jian'an Luan; Leo-Pekka Lyytikäinen; Patrik K E Magnusson; Massimo Mangino; Evelin Mihailov; May E Montasser; Martina Müller-Nurasyid; Ilja M Nolte; Jeffrey R O'Connell; Cameron D Palmer; Markus Perola; Ann-Kristin Petersen; Serena Sanna; Richa Saxena; Susan K Service; Sonia Shah; Dmitry Shungin; Carlo Sidore; Ci Song; Rona J Strawbridge; Ida Surakka; Toshiko Tanaka; Tanya M Teslovich; Gudmar Thorleifsson; Evita G Van den Herik; Benjamin F Voight; Kelly A Volcik; Lindsay L Waite; Andrew Wong; Ying Wu; Weihua Zhang; Devin Absher; Gershim Asiki; Inês Barroso; Latonya F Been; Jennifer L Bolton; Lori L Bonnycastle; Paolo Brambilla; Mary S Burnett; Giancarlo Cesana; Maria Dimitriou; Alex S F Doney; Angela Döring; Paul Elliott; Stephen E Epstein; Gudmundur Ingi Eyjolfsson; Bruna Gigante; Mark O Goodarzi; Harald Grallert; Martha L Gravito; Christopher J Groves; Göran Hallmans; Anna-Liisa Hartikainen; Caroline Hayward; Dena Hernandez; Andrew A Hicks; Hilma Holm; Yi-Jen Hung; Thomas Illig; Michelle R Jones; Pontiano Kaleebu; John J P Kastelein; Kay-Tee Khaw; Eric Kim; Global Lipids Genetics Consortium

doi:10.1038/ng.2797

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Discovery and refinement of loci associated with lipid levels

Journal article

Peer reviewed

Discovery and refinement of loci associated with lipid levels

Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, …

Nature genetics, Vol.45(11), pp.1274-1283

01/11/2013

DOI: https://doi.org/10.1038/ng.2797

PMID: 24097068

Abstract

Asian People - genetics

Black People - genetics

Cholesterol, HDL - blood

Cholesterol, HDL - genetics

Cholesterol, LDL - blood

Cholesterol, LDL - genetics

Coronary Artery Disease - blood

Coronary Artery Disease - genetics

Genetic Predisposition to Disease

Genome-Wide Association Study

Genotype

Humans

Lipids - blood

Lipids - genetics

Triglycerides - blood

Triglycerides - genetics

White People - genetics

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

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Title: Discovery and refinement of loci associated with lipid levels
Creators: Cristen J Willer - University of Michigan–Ann Arbor
Ellen M Schmidt - University of Michigan–Ann Arbor
Sebanti Sengupta - University of Michigan–Ann Arbor
Gina M Peloso - Boston University
Stefan Gustafsson - Uppsala University
Stavroula Kanoni - Wellcome Sanger Institute
Andrea Ganna - Science for Life Laboratory
Jin Chen - University of Michigan–Ann Arbor
Martin L Buchkovich - University of North Carolina at Chapel Hill
Samia Mora - Brigham and Women's Hospital
Jacques S Beckmann - University of Lausanne
Jennifer L Bragg-Gresham - University of Michigan–Ann Arbor
Hsing-Yi Chang - National Health Research Institutes
Ayşe Demirkan - Erasmus MC
Heleen M Den Hertog - Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Ron Do - Massachusetts General Hospital
Louise A Donnelly - Ninewells Hospital
Georg B Ehret - Johns Hopkins Medicine
Tõnu Esko - University of Tartu
Mary F Feitosa - Department of Genetics, Washington University School of Medicine, USA
Teresa Ferreira - Wellcome Centre for Human Genetics
Krista Fischer - University of Tartu
Pierre Fontanillas - Broad Institute
Ross M Fraser - University of Edinburgh
Daniel F Freitag - University of Cambridge
Deepti Gurdasani - Wellcome Sanger Institute
Kauko Heikkilä - University of Helsinki
Elina Hyppönen - UCL Australia
Aaron Isaacs - Erasmus MC
Anne U Jackson - University of Michigan–Ann Arbor
Åsa Johansson - Uppsala University
Toby Johnson - Queen Mary University of London
Marika Kaakinen - University of Oulu
Johannes Kettunen - University of Helsinki
Marcus E Kleber - University Hospital Heidelberg
Xiaohui Li - Cedars-Sinai Medical Center
Jian'an Luan - MRC Epidemiology Unit
Leo-Pekka Lyytikäinen - University of Tampere
Patrik K E Magnusson - Karolinska Institutet
Massimo Mangino - King's College London
Evelin Mihailov - University of Tartu
May E Montasser - University of Maryland, Baltimore
Martina Müller-Nurasyid - Ludwig-Maximilians-Universität München
Ilja M Nolte - University Medical Center Groningen
Jeffrey R O'Connell - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland
Cameron D Palmer - Broad Institute
Markus Perola - Finnish Institute for Health and Welfare
Ann-Kristin Petersen - Helmholtz Zentrum München
Serena Sanna - Institute of Genetic and Biomedical Research
Richa Saxena - Broad Institute
Susan K Service - University of California, Los Angeles
Sonia Shah - University College London
Dmitry Shungin - Umeå University
Carlo Sidore - University of Michigan–Ann Arbor
Ci Song - Science for Life Laboratory
Rona J Strawbridge - Karolinska Institutet
Ida Surakka - Institute for Molecular Medicine Finland
Toshiko Tanaka - Clinical Research Branch, National Institute Health, Baltimore, MD, USA
Tanya M Teslovich - University of Michigan–Ann Arbor
Gudmar Thorleifsson - deCODE Genetics/Amgen, 101 Reykjavik, Iceland
Evita G Van den Herik - Erasmus MC
Benjamin F Voight - University of Pennsylvania
Kelly A Volcik - The University of Texas Health Science Center at Houston
Lindsay L Waite - HudsonAlpha Institute for Biotechnology
Andrew Wong - MRC Unit for Lifelong Health and Ageing
Ying Wu - Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA
Weihua Zhang - Imperial College London
Devin Absher - HudsonAlpha Institute for Biotechnology
Gershim Asiki - Uganda Virus Research Institute
Inês Barroso - Wellcome Sanger Institute
Latonya F Been - University of Oklahoma Health Sciences Center
Jennifer L Bolton - University of Edinburgh
Lori L Bonnycastle - National Human Genome Research Institute
Paolo Brambilla - University of Milano-Bicocca
Mary S Burnett - MedStar Health
Giancarlo Cesana - University of Milano-Bicocca
Maria Dimitriou - Harokopio University of Athens
Alex S F Doney - Ninewells Hospital
Angela Döring - Helmholtz Zentrum München
Paul Elliott - Imperial College London
Stephen E Epstein - MedStar Health
Gudmundur Ingi Eyjolfsson - The Laboratory in Mjodd, 108 Reykjavik, Iceland
Bruna Gigante - Karolinska Institutet
Mark O Goodarzi - Cedars-Sinai Medical Center
Harald Grallert - Helmholtz Zentrum München
Martha L Gravito - University of Oklahoma Health Sciences Center
Christopher J Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Göran Hallmans - Umeå University
Anna-Liisa Hartikainen - Oulu University Hospital
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Dena Hernandez - National Institute on Aging
Andrew A Hicks - Eurac Research
Hilma Holm - deCODE Genetics
Yi-Jen Hung - National Defense Medical Center
Thomas Illig - Helmholtz Zentrum München
Michelle R Jones - Cedars-Sinai Medical Center
Pontiano Kaleebu - Uganda Virus Research Institute
John J P Kastelein - Academic Medical Center
Kay-Tee Khaw - University of Cambridge
Eric Kim - Cedars-Sinai Medical Center
Global Lipids Genetics Consortium
Publication Details: Nature genetics, Vol.45(11), pp.1274-1283
Date published: 01/11/2013
Grant note: G0401527 / Medical Research Council MC_U106188470 / Medical Research Council R01 DK072193 / NIDDK NIH HHS CZB/4/672 / Chief Scientist Office R01 HL109946 / NHLBI NIH HHS 090532 / Wellcome Trust PG/08/094/26019 / British Heart Foundation 100891 / Wellcome Trust RG/08/008/25291 / British Heart Foundation CZB/4/710 / Chief Scientist Office
Identifiers: 99928715402346
Academic Unit: Institute for Sustainability; Surrey Institute for People-Centred AI; School of Biosciences
Language: English
Resource Type: Journal article

Discovery and refinement of loci associated with lipid levels

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