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

Tuomas O. Kilpelainen; Amy R. Bentley; Raymond Noordam; Yun Ju Sung; Karen Schwander; Thomas W. Winkler; Hermina Jakupovic; Daniel I. Chasman; Alisa Manning; Ioanna Ntalla; Hugues Aschard; Michael R. Brown; Lisa de las Fuentes; Nora Franceschini; Xiuqing Guo; Dina Vojinovic; Stella Aslibekyan; Mary F. Feitosa; Minjung Kho; Solomon K. Musani; Melissa Richard; Heming Wang; Zhe Wang; Traci M. Bartz; Lawrence F. Bielak; Archie Campbell; Rajkumar Dorajoo; Virginia Fisher; Fernando P. Hartwig; Andrea R. V. R. Horimoto; Changwei Li; Kurt K. Lohman; Jonathan Marten; Xueling Sim; Albert V. Smith; Salman M. Tajuddin; Maris Alver; Marzyeh Amini; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Evangelos Evangelou; Chuan Gao; Mariaelisa Graff; Sarah E. Harris; Meian He; Fang-Chi Hsu; Anne U. Jackson; Jing Hua Zhao; Aldi T. Kraja; Brigitte Kuehnel; Federica Laguzzi; Leo-Pekka Lyytikainen; Ilja M. Nolte; Rainer Rauramaa; Muhammad Riaz; Antonietta Robino; Rico Rueedi; Heather M. Stringham; Fumihiko Takeuchi; Peter J. van der Most; Tibor V. Varga; Niek Verweij; Erin B. Ware; Wanqing Wen; Xiaoyin Li; Lisa R. Yanek; Najaf Amin; Donna K. Arnett; Eric Boerwinkle; Marco Brumat; Brian Cade; Mickael Canouil; Yii-Der Ida Chen; Maria Pina Concas; John Connell; Renee de Mutsert; H. Janaka de Silva; Paul S. de Vries; Ayse Demirkan; Jingzhong Ding; Charles B. Eaton; Jessica D. Faul; Yechiel Friedlander; Kelley P. Gabriel; Mohsen Ghanbari; Franco Giulianini; Chi Charles Gu; Dongfeng Gu; Tamara B. Harris; Jiang He; Sami Heikkinen; Chew-Kiat Heng; Steven C. Hunt; M. Arfan Ikram; Jost B. Jonas; Woon-Puay Koh; Pirjo Komulainen; Jose E. Krieger; Stephen B. Kritchevsky; Zoltan Kutalik; Johanna Kuusisto; Carl D. Langefeld; Claudia Langenberg; Lenore J. Launer; Karin Leander; Rozenn N. Lemaitre; Cora E. Lewis; Jingjing Liang; Behrooz Z. Alizadeh; H. Marike Boezen; Lude Franke; Gerjan Navis; Marianne Rots; Morris Swertz; Bruce H. R. Wolffenbuttel; Cisca Wijmenga; Jianjun Liu; Reedik Magi; Ani Manichaikul; Thomas Meitinger; Andres Metspalu; Yuri Milaneschi; Karen L. Mohlke; Thomas H. Mosley; Alison D. Murray; Mike A. Nalls; Ei-Ei Khaing Nang; Christopher P. Nelson; Sotoodehnia Nona; Jill M. Norris; Chiamaka Vivian Nwuba; Jeff O'Connell; Nicholette D. Palmer; George J. Papanicolau; Raha Pazoki; Nancy L. Pedersen; Annette Peters; Patricia A. Peyser; Ozren Polasek; David J. Porteous; Alaitz Poveda; Olli T. Raitakari; Stephen S. Rich; Neil Risch; Jennifer G. Robinson; Lynda M. Rose; Igor Rudan; Pamela J. Schreiner; Robert A. Scott; Stephen S. Sidney; Mario Sims; Jennifer A. Smith; Harold Snieder; Tamar Sofer; John M. Starr; Barbara Sternfeld; Konstantin Strauch; Hua Tang; Kent D. Taylor; Michael Y. Tsai; Jaakko Tuomilehto; Andre G. Uitterlinden; M. Yldau van der Ende; Diana van Heemst; Trudy Voortman; Melanie Waldenberger; Patrik Wennberg; Gregory Wilson; Yong-Bing Xiang; Jie Yao; Caizheng Yu; Jian-Min Yuan; Wei Zhao; Alan B. Zonderman; Diane M. Becker; Michael Boehnke; Donald W. Bowden; Ulf de Faire; Ian J. Deary; Paul Elliott; Tonu Esko; Barry I. Freedman; Philippe Froguel; Paolo Gasparini; Christian Gieger; Norihiro Kato; Markku Laakso; Timo A. Lakka; Terho Lehtimaki; Patrik K. E. Magnusson; Albertine J. Oldehinkel; Brenda W. J. H. Penninx; Nilesh J. Samani; Xiao-Ou Shu; Pim van der Harst; Jana V. Van Vliet-Ostaptchouk; Peter Vollenweider; Lynne E. Wagenknecht; Ya X. Wang; Nicholas J. Wareham; David R. Weir; Tangchun Wu; Wei Zheng; Xiaofeng Zhu; Michele K. Evans; Paul W. Franks; Vilmundur Gudnason; Caroline Hayward; Bernardo L. Horta; Tanika N. Kelly; Yongmei Liu; Kari E. North; Alexandre C. Pereira; Paul M. Ridker; E. Shyong Tai; Rob M. van Dam; Ervin R. Fox; Sharon L. R. Kardia; Ching-Ti Liu; Dennis O. Mook-Kanamori; Michael A. Province; Susan Redline; Cornelia M. van Duijn; Jerome I. Rotter; Charles B. Kooperberg; W. James Gauderman; Bruce M. Psaty; Kenneth Rice; Patricia B. Munroe; Myriam Fornage; L. Adrienne Cupples; Charles N. Rotimi; Alanna C. Morrison; Dabeeru C. Rao; Ruth J. F. Loos; Lifelines Cohort Study

doi:10.1038/s41467-018-08008-w

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

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

Tuomas O. Kilpelainen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupovic, Daniel I. Chasman, Alisa Manning, Ioanna Ntalla, …

Nature communications, Vol.10(1), pp.376-376

2019

DOI: https://doi.org/10.1038/s41467-018-08008-w

PMCID: PMC6342931

PMID: 30670697

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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.

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Title: Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Creators - without role: Tuomas O. Kilpelainen - University of Copenhagen
Amy R. Bentley - NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA
Raymond Noordam - Leiden University
Yun Ju Sung - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
Karen Schwander - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
Thomas W. Winkler - University of Regensburg
Hermina Jakupovic - University of Copenhagen
Daniel I. Chasman - Brigham and Women's Hospital
Alisa Manning - Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA
Ioanna Ntalla - Queen Mary University of London
Hugues Aschard - Supreme Council Of Health
Michael R. Brown - Supreme Council Of Health
Lisa de las Fuentes - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
Nora Franceschini - Supreme Council Of Health
Xiuqing Guo - Biomed Research Institute
Dina Vojinovic - College Station Medical Center
Stella Aslibekyan - University of Alabama
Mary F. Feitosa - Supreme Council Of Health
Minjung Kho - Supreme Council Of Health
Solomon K. Musani - University of Mississippi
Melissa Richard - Supreme Council Of Health
Heming Wang - Circadian
Zhe Wang - Supreme Council Of Health
Traci M. Bartz - University of Washington
Lawrence F. Bielak - Supreme Council Of Health
Archie Campbell - University of Edinburgh
Rajkumar Dorajoo - Genome Institute of Singapore
Virginia Fisher - Boston University
Fernando P. Hartwig - Univ Fed Pelotas, Postgrad Program Epidemiol, BR-96020220 Pelotas, RS, Brazil
Andrea R. V. R. Horimoto - Supreme Council Of Health
Changwei Li - Biostat
Kurt K. Lohman - Wake Forest University
Jonathan Marten - University of Edinburgh
Xueling Sim - Supreme Council Of Health
Albert V. Smith - Iceland Heart Assoc, IS-201 Kopavogur, Iceland
Salman M. Tajuddin - NIA, Hlth Dispar Res Sect, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA
Maris Alver - University of Tartu
Marzyeh Amini - University of Groningen
Mathilde Boissel - Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, F-59000 Lille, France
Jin Fang Chai - Supreme Council Of Health
Xu Chen - Karolinska Institutet
Jasmin Divers - Supreme Council Of Health
Evangelos Evangelou - Biostat
Chuan Gao - Supreme Council Of Health
Mariaelisa Graff - Supreme Council Of Health
Sarah E. Harris - University of Edinburgh
Meian He - College Station Medical Center
Fang-Chi Hsu - Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA
Anne U. Jackson - Biostat
Jing Hua Zhao - University of Cambridge
Aldi T. Kraja - Supreme Council Of Health
Brigitte Kuehnel - Helmholtz Zentrum München
Federica Laguzzi - Karolinska Institutet
Leo-Pekka Lyytikainen - Fimlab
Ilja M. Nolte - University of Groningen
Rainer Rauramaa - College Station Medical Center
Muhammad Riaz - Infant
Antonietta Robino - Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy
Rico Rueedi - University of Lausanne
Heather M. Stringham - Biostat
Fumihiko Takeuchi - College Station Medical Center
Peter J. van der Most - University of Groningen
Tibor V. Varga - Lund University
Niek Verweij - University of Groningen
Erin B. Ware - Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA
Wanqing Wen - Vanderbilt University
Xiaoyin Li - Case Western Reserve University
Lisa R. Yanek - Johns Hopkins University
Najaf Amin - College Station Medical Center
Donna K. Arnett - University of Kentucky
Eric Boerwinkle - Supreme Council Of Health
Marco Brumat - University of Trieste
Brian Cade - Circadian
Mickael Canouil - Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, F-59000 Lille, France
Yii-Der Ida Chen - Biomed Research Institute
Maria Pina Concas - Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy
John Connell - University of Dundee
Renee de Mutsert - Leiden University
H. Janaka de Silva - University of Kelaniya
Paul S. de Vries - Supreme Council Of Health
Ayse Demirkan - College Station Medical Center
Jingzhong Ding - Supreme Council Of Health
Charles B. Eaton - Brown University
Jessica D. Faul - Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA
Yechiel Friedlander - Hebrew University of Jerusalem
Kelley P. Gabriel - Supreme Council Of Health
Mohsen Ghanbari - College Station Medical Center
Franco Giulianini - Brigham and Women's Hospital
Chi Charles Gu - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
Dongfeng Gu - College Station Medical Center
Tamara B. Harris - NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA
Jiang He - Tulane University
Sami Heikkinen - University of Eastern Finland
Chew-Kiat Heng - Supreme Council Of Health
Steven C. Hunt - University of Utah
M. Arfan Ikram - College Station Medical Center
Jost B. Jonas - Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, D-98167 Mannheim, Germany
Woon-Puay Koh - Supreme Council Of Health
Pirjo Komulainen - College Station Medical Center
Jose E. Krieger - Supreme Council Of Health
Stephen B. Kritchevsky - Supreme Council Of Health
Zoltan Kutalik - Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland
Johanna Kuusisto - University of Eastern Finland
Carl D. Langefeld - Supreme Council Of Health
Claudia Langenberg - University of Cambridge
Lenore J. Launer - NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA
Karin Leander - Karolinska Institutet
Rozenn N. Lemaitre - University of Washington
Cora E. Lewis - University of Alabama
Jingjing Liang - Case Western Reserve University
Behrooz Z. Alizadeh - University of Groningen
H. Marike Boezen - University of Groningen
Lude Franke - University of Groningen
Gerjan Navis - University of Groningen
Marianne Rots - University of Groningen
Morris Swertz - University of Groningen
Bruce H. R. Wolffenbuttel - University of Groningen
Cisca Wijmenga - University of Groningen
Jianjun Liu - Genome Institute of Singapore
Reedik Magi - University of Tartu
Ani Manichaikul - University of Virginia
Thomas Meitinger - Helmholtz Zentrum München
Andres Metspalu - University of Tartu
Yuri Milaneschi - University of Amsterdam
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA
Thomas H. Mosley - University of Mississippi
Alison D. Murray - University of Aberdeen
Mike A. Nalls - NIA, Mol Genet Sect, Lab Neurogenet, Bethesda, MD 20892 USA
Ei-Ei Khaing Nang - Supreme Council Of Health
Christopher P. Nelson - University of Leicester
Sotoodehnia Nona - University of Washington
Jill M. Norris - University of Colorado Denver
Chiamaka Vivian Nwuba - University of Copenhagen
Jeff O'Connell - Supreme Council Of Health
Nicholette D. Palmer - Supreme Council Of Health
George J. Papanicolau - NHLBI, Epidemiol Branch, NIH, Bethesda, MD 20892 USA
Raha Pazoki - Biostat
Nancy L. Pedersen - Karolinska Institutet
Annette Peters - Helmholtz Zentrum München
Patricia A. Peyser - Supreme Council Of Health
Ozren Polasek - University of Split
David J. Porteous - University of Edinburgh
Alaitz Poveda - Lund University
Olli T. Raitakari - College Station Medical Center
Stephen S. Rich - College Station Medical Center
Neil Risch - Biostat
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
Mario Sims - University of Mississippi
Jennifer A. Smith - Supreme Council Of Health
Harold Snieder - University of Groningen
Tamar Sofer - Supreme Council Of Health
John M. Starr - University of Edinburgh
Barbara Sternfeld - Kaiser Permanente
Konstantin Strauch - Helmholtz Zentrum München
Hua Tang - Stanford University
Kent D. Taylor - Biomed Research Institute
Michael Y. Tsai - University of Minnesota
Jaakko Tuomilehto - Natl Inst Hlth & Welf, Publ Hlth Solut, Helsinki 00271, Finland
Andre G. Uitterlinden - College Station Medical Center
M. Yldau van der Ende - University of Groningen
Diana van Heemst - Leiden University
Trudy Voortman - College Station Medical Center
Melanie Waldenberger - Helmholtz Zentrum München
Patrik Wennberg - Umeå University
Gregory Wilson - Jackson State University
Yong-Bing Xiang - Shanghai Jiao Tong University
Jie Yao - Biomed Research Institute
Caizheng Yu - College Station Medical Center
Jian-Min Yuan - University of Pittsburgh
Wei Zhao - Supreme Council Of Health
Alan B. Zonderman - NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA
Diane M. Becker - Johns Hopkins University
Michael Boehnke - Biostat
Donald W. Bowden - Supreme Council Of Health
Ulf de Faire - Karolinska Institutet
Ian J. Deary - University of Edinburgh
Paul Elliott - Biostat
Tonu Esko - University of Tartu
Barry I. Freedman - Supreme Council Of Health
Philippe Froguel - University of Lille
Paolo Gasparini - Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy
Christian Gieger - Helmholtz Zentrum München
Norihiro Kato - College Station Medical Center
Markku Laakso - University of Eastern Finland
Timo A. Lakka - University of Lausanne
Terho Lehtimaki - Fimlab
Patrik K. E. Magnusson - Karolinska Institutet
Albertine J. Oldehinkel - University of Groningen
Brenda W. J. H. Penninx - University of Amsterdam
Nilesh J. Samani - University of Leicester
Xiao-Ou Shu - Vanderbilt University
Pim van der Harst - University of Groningen
Jana V. Van Vliet-Ostaptchouk - University of Groningen
Peter Vollenweider - College Station Medical Center
Lynne E. Wagenknecht - Supreme Council Of Health
Ya X. Wang - College Station Medical Center
Nicholas J. Wareham - University of Cambridge
David R. Weir - Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA
Tangchun Wu - College Station Medical Center
Wei Zheng - Vanderbilt University
Xiaofeng Zhu - Case Western Reserve University
Michele K. Evans - NIA, Hlth Dispar Res Sect, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA
Paul W. Franks - Lund University
Vilmundur Gudnason - Iceland Heart Assoc, IS-201 Kopavogur, Iceland
Caroline Hayward - University of Edinburgh
Bernardo L. Horta - Univ Fed Pelotas, Postgrad Program Epidemiol, BR-96020220 Pelotas, RS, Brazil
Tanika N. Kelly - Tulane University
Yongmei Liu - Wake Forest University
Kari E. North - Supreme Council Of Health
Alexandre C. Pereira - Supreme Council Of Health
Paul M. Ridker - Brigham and Women's Hospital
E. Shyong Tai - Supreme Council Of Health
Rob M. van Dam - Supreme Council Of Health
Ervin R. Fox - University of Mississippi
Sharon L. R. Kardia - Supreme Council Of Health
Ching-Ti Liu - Boston University
Dennis O. Mook-Kanamori - Leiden University
Michael A. Province - Supreme Council Of Health
Susan Redline - Circadian
Cornelia M. van Duijn - College Station Medical Center
Jerome I. Rotter - Biomed Research Institute
Charles B. Kooperberg - University of Washington
W. James Gauderman - Biostat
Bruce M. Psaty - Kaiser Permanente
Kenneth Rice - University of Washington
Patricia B. Munroe - Queen Mary University of London
Myriam Fornage - Supreme Council Of Health
L. Adrienne Cupples - Boston University
Charles N. Rotimi - NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA
Alanna C. Morrison - Supreme Council Of Health
Dabeeru C. Rao - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
Ruth J. F. Loos - Supreme Council Of Health
Lifelines Cohort Study
Publication Details: Nature communications, Vol.10(1), pp.376-376
Publisher: Springer Nature
Number of pages: 11
Grant note: R01HL142302 / 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) P2CHD050924 / 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) ZIAAG000513 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) P01CA196569 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30DK056341 / 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) R56HG010297 / 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) R01HL118305 / US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health BB/F019394/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) MR/R023484/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9937475108331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article