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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author

Listed:
  • Tuomas O. Kilpeläinen

    (University of Copenhagen
    The Icahn School of Medicine at Mount Sinai)

  • Amy R. Bentley

    (National Institutes of Health)

  • Raymond Noordam

    (Leiden University Medical Center)

  • Yun Ju Sung

    (Washington University School of Medicine)

  • Karen Schwander

    (Washington University School of Medicine)

  • Thomas W. Winkler

    (University of Regensburg)

  • Hermina Jakupović

    (University of Copenhagen)

  • Daniel I. Chasman

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Alisa Manning

    (Massachusetts General Hospital
    Harvard Medical School)

  • Ioanna Ntalla

    (Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Hugues Aschard

    (Harvard School of Public Health
    Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur)

  • Michael R. Brown

    (The University of Texas Health Science Center at Houston)

  • Lisa las Fuentes

    (Washington University School of Medicine
    Washington University)

  • Nora Franceschini

    (Epidemiology, University of North Carolina Gillings School of Global Public Health)

  • Xiuqing Guo

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Dina Vojinovic

    (Erasmus University Medical Center)

  • Stella Aslibekyan

    (University of Alabama at Birmingham)

  • Mary F. Feitosa

    (Washington University School of Medicine)

  • Minjung Kho

    (University of Michigan)

  • Solomon K. Musani

    (University of Mississippi Medical Center)

  • Melissa Richard

    (University of Texas Health Science Center at Houston)

  • Heming Wang

    (Brigham and Women’s Hospital)

  • Zhe Wang

    (The University of Texas Health Science Center at Houston)

  • Traci M. Bartz

    (University of Washington)

  • Lawrence F. Bielak

    (University of Michigan)

  • Archie Campbell

    (University of Edinburgh)

  • Rajkumar Dorajoo

    (Agency for Science Technology and Research)

  • Virginia Fisher

    (Biostatistics, Boston University School of Public Health)

  • Fernando P. Hartwig

    (Federal University of Pelotas
    University of Bristol)

  • Andrea R. V. R. Horimoto

    (University of São Paulo Medical School)

  • Changwei Li

    (University of Giorgia at Athens College of Public Health)

  • Kurt K. Lohman

    (Wake Forest University Health Sciences)

  • Jonathan Marten

    (University of Edinburgh)

  • Xueling Sim

    (National University Health System and National University of Singapore)

  • Albert V. Smith

    (Icelandic Heart Association
    University of Michigan)

  • Salman M. Tajuddin

    (National Institute on Aging, National Institutes of Health)

  • Maris Alver

    (University of Tartu)

  • Marzyeh Amini

    (University Medical Center Groningen)

  • Mathilde Boissel

    (Institut Pasteur de Lille, University of Lille)

  • Jin Fang Chai

    (National University Health System and National University of Singapore)

  • Xu Chen

    (Karolinska Institutet, Stockholm)

  • Jasmin Divers

    (Wake Forest School of Medicine)

  • Evangelos Evangelou

    (Imperial College London
    University of Ioannina Medical School)

  • Chuan Gao

    (Wake Forest School of Medicine)

  • Mariaelisa Graff

    (Epidemiology, University of North Carolina Gillings School of Global Public Health)

  • Sarah E. Harris

    (University of Edinburgh
    The University of Edinburgh)

  • Meian He

    (Huazhong University of Science and Technology)

  • Fang-Chi Hsu

    (Wake Forest School of Medicine)

  • Anne U. Jackson

    (University of Michigan)

  • Jing Hua Zhao

    (University of Cambridge)

  • Aldi T. Kraja

    (Washington University School of Medicine)

  • Brigitte Kühnel

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    German Research Center for Environmental Health)

  • Federica Laguzzi

    (Karolinska Institutet)

  • Leo-Pekka Lyytikäinen

    (Fimlab Laboratories
    University of Tampere)

  • Ilja M. Nolte

    (University Medical Center Groningen)

  • Rainer Rauramaa

    (Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine)

  • Muhammad Riaz

    (The Infant Mortality and Morbidity Studies (TIMMS))

  • Antonietta Robino

    (Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”)

  • Rico Rueedi

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Heather M. Stringham

    (University of Michigan)

  • Fumihiko Takeuchi

    (National Center for Global Health and Medicine)

  • Peter J. Most

    (University Medical Center Groningen)

  • Tibor V. Varga

    (Skåne University Hospital)

  • Niek Verweij

    (University of Groningen, University Medical Center Groningen, Department of Cardiology)

  • Erin B. Ware

    (University of Michigan)

  • Wanqing Wen

    (Vanderbilt University School of Medicine)

  • Xiaoyin Li

    (Case Western Reserve University)

  • Lisa R. Yanek

    (Johns Hopkins University School of Medicine)

  • Najaf Amin

    (Erasmus University Medical Center)

  • Donna K. Arnett

    (University of Kentucky College of Public Health)

  • Eric Boerwinkle

    (The University of Texas Health Science Center at Houston
    Baylor College of Medicine)

  • Marco Brumat

    (University of Trieste)

  • Brian Cade

    (Brigham and Women’s Hospital)

  • Mickaël Canouil

    (Institut Pasteur de Lille, University of Lille)

  • Yii-Der Ida Chen

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Maria Pina Concas

    (Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”)

  • John Connell

    (University of Dundee)

  • Renée Mutsert

    (Leiden University Medical Center)

  • H. Janaka Silva

    (University of Kelaniya)

  • Paul S. Vries

    (The University of Texas Health Science Center at Houston)

  • Ayşe Demirkan

    (Erasmus University Medical Center)

  • Jingzhong Ding

    (Wake Forest School of Medicine)

  • Charles B. Eaton

    (Alpert Medical School of Brown University)

  • Jessica D. Faul

    (University of Michigan)

  • Yechiel Friedlander

    (Hebrew University-Hadassah Medical Center)

  • Kelley P. Gabriel

    (The University of Texas Health Science Center at Austin)

  • Mohsen Ghanbari

    (Erasmus University Medical Center
    Mashhad University of Medical Sciences)

  • Franco Giulianini

    (Brigham and Women’s Hospital)

  • Chi Charles Gu

    (Washington University School of Medicine)

  • Dongfeng Gu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Tamara B. Harris

    (National Institutes of Health)

  • Jiang He

    (Epidemiology, Tulane University School of Public Health and Tropical Medicine
    Medicine, Tulane University School of Medicine)

  • Sami Heikkinen

    (University of Eastern Finland
    University of Eastern Finland)

  • Chew-Kiat Heng

    (National University of Singapore
    National University Health System)

  • Steven C. Hunt

    (University of Utah
    Weill Cornell Medicine)

  • M. Arfan Ikram

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Jost B. Jonas

    (University Heidelberg
    Capital Medical University)

  • Woon-Puay Koh

    (National University Health System and National University of Singapore
    Duke-NUS Medical School)

  • Pirjo Komulainen

    (Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine)

  • Jose E. Krieger

    (University of São Paulo Medical School)

  • Stephen B. Kritchevsky

    (Wake Forest School of Medicine)

  • Zoltán Kutalik

    (Swiss Institute of Bioinformatics
    Lausanne University Hospital)

  • Johanna Kuusisto

    (University of Eastern Finland)

  • Carl D. Langefeld

    (Wake Forest School of Medicine)

  • Claudia Langenberg

    (University of Cambridge)

  • Lenore J. Launer

    (National Institutes of Health)

  • Karin Leander

    (Karolinska Institutet)

  • Rozenn N. Lemaitre

    (University of Washington)

  • Cora E. Lewis

    (University of Alabama at Birmingham, School of Medicine)

  • Jingjing Liang

    (Case Western Reserve University)

  • Jianjun Liu

    (Agency for Science Technology and Research
    National University of Singapore)

  • Reedik Mägi

    (University of Tartu)

  • Ani Manichaikul

    (University of Virginia School of Medicine)

  • Thomas Meitinger

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    Technische Universität München)

  • Andres Metspalu

    (University of Tartu)

  • Yuri Milaneschi

    (VU University Medical Center)

  • Karen L. Mohlke

    (University of North Carolina)

  • Thomas H. Mosley

    (University of Mississippi)

  • Alison D. Murray

    (University of Aberdeen)

  • Mike A. Nalls

    (National Institute on Aging
    Data Tecnica International)

  • Ei-Ei Khaing Nang

    (National University Health System and National University of Singapore)

  • Christopher P. Nelson

    (University of Leicester
    Glenfield Hospital)

  • Sotoodehnia Nona

    (University of Washington)

  • Jill M. Norris

    (University of Colorado Denver)

  • Chiamaka Vivian Nwuba

    (University of Copenhagen)

  • Jeff O’Connell

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Nicholette D. Palmer

    (Wake Forest School of Medicine)

  • George J. Papanicolau

    (National Institutes of Health)

  • Raha Pazoki

    (Imperial College London)

  • Nancy L. Pedersen

    (Karolinska Institutet, Stockholm)

  • Annette Peters

    (German Research Center for Environmental Health
    partner site Munich Heart Alliance)

  • Patricia A. Peyser

    (University of Michigan)

  • Ozren Polasek

    (University of Split
    Psychiatric Hospital “Sveti Ivan”
    Gen-Info Ltd.)

  • David J. Porteous

    (University of Edinburgh
    The University of Edinburgh)

  • Alaitz Poveda

    (Skåne University Hospital)

  • Olli T. Raitakari

    (Turku University Hospital
    University of Turku)

  • Stephen S. Rich

    (University of Virginia School of Medicine)

  • Neil Risch

    (University of California)

  • Jennifer G. Robinson

    (University of Iowa)

  • Lynda M. Rose

    (Brigham and Women’s Hospital)

  • Igor Rudan

    (University of Edinburgh)

  • Pamela J. Schreiner

    (University of Minnesota)

  • Robert A. Scott

    (University of Cambridge)

  • Stephen S. Sidney

    (Kaiser Permanente Washington, Health Research Institute)

  • Mario Sims

    (University of Mississippi Medical Center)

  • Jennifer A. Smith

    (University of Michigan
    University of Michigan)

  • Harold Snieder

    (University Medical Center Groningen)

  • Tamar Sofer

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • John M. Starr

    (The University of Edinburgh
    The University of Edinburgh)

  • Barbara Sternfeld

    (Kaiser Permanente Washington, Health Research Institute)

  • Konstantin Strauch

    (German Research Center for Environmental Health
    Ludwig-Maximilians-Universitat Munchen)

  • Hua Tang

    (Stanford University)

  • Kent D. Taylor

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Michael Y. Tsai

    (University of Minnesota)

  • Jaakko Tuomilehto

    (National Institute for Health and Welfare
    King Abdulaziz University)

  • André G. Uitterlinden

    (Erasmus University Medical Center)

  • M. Yldau Ende

    (University of Groningen, University Medical Center Groningen, Department of Cardiology)

  • Diana Heemst

    (Leiden University Medical Center)

  • Trudy Voortman

    (Erasmus University Medical Center)

  • Melanie Waldenberger

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    German Research Center for Environmental Health)

  • Patrik Wennberg

    (Umeå University)

  • Gregory Wilson

    (Jackson State University)

  • Yong-Bing Xiang

    (Shanghai Jiaotong University School of Medicine)

  • Jie Yao

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Caizheng Yu

    (Huazhong University of Science and Technology)

  • Jian-Min Yuan

    (University of Pittsburgh
    UPMC Hillman Cancer, University of Pittsburgh)

  • Wei Zhao

    (University of Michigan)

  • Alan B. Zonderman

    (National Institutes of Health)

  • Diane M. Becker

    (Johns Hopkins University School of Medicine)

  • Michael Boehnke

    (University of Michigan)

  • Donald W. Bowden

    (Wake Forest School of Medicine)

  • Ulf Faire

    (Karolinska Institutet)

  • Ian J. Deary

    (The University of Edinburgh
    Psychology, The University of Edinburgh)

  • Paul Elliott

    (Imperial College London
    Imperial College London)

  • Tõnu Esko

    (University of Tartu
    Broad Institute of the Massachusetts Institute of Technology and Harvard University)

  • Barry I. Freedman

    (Wake Forest School of Medicine)

  • Philippe Froguel

    (Institut Pasteur de Lille, University of Lille
    Imperial College London)

  • Paolo Gasparini

    (Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”
    University of Trieste)

  • Christian Gieger

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD e.V.))

  • Norihiro Kato

    (National Center for Global Health and Medicine)

  • Markku Laakso

    (University of Eastern Finland)

  • Timo A. Lakka

    (Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine
    University of Eastern Finland
    Kuopio University Hospital)

  • Terho Lehtimäki

    (Fimlab Laboratories
    University of Tampere)

  • Patrik K. E. Magnusson

    (Karolinska Institutet, Stockholm)

  • Albertine J. Oldehinkel

    (University Medical Center Groningen)

  • Brenda W. J. H. Penninx

    (VU University Medical Center)

  • Nilesh J. Samani

    (University of Leicester
    Glenfield Hospital)

  • Xiao-Ou Shu

    (Vanderbilt University School of Medicine)

  • Pim Harst

    (University of Groningen, University Medical Center Groningen, Department of Cardiology
    University Medical Center Groningen
    ICIN-Netherlands Heart Institute)

  • Jana V. Vliet-Ostaptchouk

    (University Medical Center Groningen)

  • Peter Vollenweider

    (Lausanne University Hospital)

  • Lynne E. Wagenknecht

    (Wake Forest School of Medicine)

  • Ya X. Wang

    (Capital Medical University)

  • Nicholas J. Wareham

    (University of Cambridge)

  • David R. Weir

    (University of Michigan)

  • Tangchun Wu

    (Huazhong University of Science and Technology)

  • Wei Zheng

    (Vanderbilt University School of Medicine)

  • Xiaofeng Zhu

    (Case Western Reserve University)

  • Michele K. Evans

    (National Institute on Aging, National Institutes of Health)

  • Paul W. Franks

    (Skåne University Hospital
    Umeå University
    Harvard University
    University of Oxford)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Caroline Hayward

    (University of Edinburgh)

  • Bernardo L. Horta

    (Federal University of Pelotas)

  • Tanika N. Kelly

    (Epidemiology, Tulane University School of Public Health and Tropical Medicine)

  • Yongmei Liu

    (Wake Forest University Health Sciences)

  • Kari E. North

    (Epidemiology, University of North Carolina Gillings School of Global Public Health)

  • Alexandre C. Pereira

    (University of São Paulo Medical School)

  • Paul M. Ridker

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • E. Shyong Tai

    (National University Health System and National University of Singapore
    Duke-NUS Medical School
    National University of Singapore)

  • Rob M. Dam

    (National University Health System and National University of Singapore
    National University of Singapore)

  • Ervin R. Fox

    (University of Mississippi Medical Center)

  • Sharon L. R. Kardia

    (University of Michigan)

  • Ching-Ti Liu

    (Biostatistics, Boston University School of Public Health)

  • Dennis O. Mook-Kanamori

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Michael A. Province

    (Washington University School of Medicine)

  • Susan Redline

    (Brigham and Women’s Hospital)

  • Cornelia M. Duijn

    (Erasmus University Medical Center)

  • Jerome I. Rotter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Charles B. Kooperberg

    (University of Washington School of Public Health)

  • W. James Gauderman

    (University of Southern California)

  • Bruce M. Psaty

    (Kaiser Permanente Washington, Health Research Institute
    University of Washington)

  • Kenneth Rice

    (University of Washington)

  • Patricia B. Munroe

    (Barts and The London School of Medicine and Dentistry, Queen Mary University of London
    Queen Mary University of London, Charterhouse Square)

  • Myriam Fornage

    (University of Texas Health Science Center at Houston)

  • L. Adrienne Cupples

    (Biostatistics, Boston University School of Public Health
    NHLBI Framingham Heart Study)

  • Charles N. Rotimi

    (National Institutes of Health)

  • Alanna C. Morrison

    (The University of Texas Health Science Center at Houston)

  • Dabeeru C. Rao

    (Washington University School of Medicine)

  • Ruth J. F. Loos

    (The Charles Bronfman Institute for Personalized Medicine
    The Mindich Child Health and Development Institute)

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

Suggested Citation

  • Tuomas O. Kilpeläinen & Amy R. Bentley & Raymond Noordam & Yun Ju Sung & Karen Schwander & Thomas W. Winkler & Hermina Jakupović & Daniel I. Chasman & Alisa Manning & Ioanna Ntalla & Hugues Aschard & , 2019. "Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08008-w
    DOI: 10.1038/s41467-018-08008-w
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