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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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, 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 Kühnel, Federica Laguzzi, Leo-Pekka Lyytikäinen, 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, Mickaël Canouil, Yii-Der Ida Chen, Maria Pina Concas, John Connell, Renée de Mutsert, H. Janaka de Silva, Paul S. de Vries, Ayşe 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, Zoltán Kutalik, Johanna Kuusisto, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Karin Leander, Rozenn N. Lemaitre, Cora E. Lewis, Jingjing Liang, , Jianjun Liu, Reedik Mägi, 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, André 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, Tõnu Esko, Barry I. Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Norihiro Kato, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, 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

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. More... »

PAGES

376

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

10

Author Affiliations

  • Icahn School of Medicine at Mount Sinai
  • National Human Genome Research Institute
  • Leiden University Medical Center
  • Washington University in St. Louis
  • University of Regensburg
  • University of Copenhagen
  • Harvard University
  • Queen Mary University of London
  • Institut Pasteur
  • The University of Texas Health Science Center at Houston
  • University of North Carolina at Chapel Hill
  • Harbor–UCLA Medical Center
  • Erasmus University Medical Center
  • University of Alabama at Birmingham
  • University of Michigan–Ann Arbor
  • University of Mississippi Medical Center
  • Brigham and Women's Hospital
  • University of Washington
  • University of Edinburgh
  • Genome Institute of Singapore
  • Boston University
  • University of Bristol
  • University of Sao Paulo
  • Wake Forest Baptist Medical Center
  • National University Health System
  • National Institute on Aging
  • University of Tartu
  • University Medical Center Groningen
  • Lille 1 University
  • Karolinska Institute
  • Wake Forest University
  • University of Ioannina
  • Huazhong University of Science and Technology
  • University of Cambridge
  • Helmholtz Zentrum München
  • University of Tampere
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University of Leicester
  • IRCCS Materno Infantile Burlo Garofolo
  • Swiss Institute of Bioinformatics
  • National Center For Global Health and Medicine
  • Skåne University Hospital
  • Vanderbilt University
  • Case Western Reserve University
  • Johns Hopkins University
  • University of Kentucky
  • Baylor College of Medicine
  • University of Trieste
  • Brown University
  • Hadassah Medical Center
  • The University of Texas Health Science Center
  • Mashhad University of Medical Sciences
  • Peking Union Medical College Hospital
  • National Institutes of Health
  • Tulane University
  • University of Eastern Finland
  • University of Utah
  • Capital Medical University
  • National University of Singapore
  • Institute of Social and Preventive Medicine
  • University of Virginia
  • Technical University Munich
  • VU University Medical Center
  • University of Mississippi
  • University of Aberdeen
  • Glenfield Hospital
  • University of Colorado Anschutz Medical Campus
  • University of Maryland, Baltimore
  • Imperial College London
  • German Centre for Cardiovascular Research
  • University of Split
  • University of Turku
  • University of California, San Francisco
  • University of Iowa
  • University of Minnesota
  • Kaiser Permanente Washington Health Research Institute
  • Ludwig Maximilian University of Munich
  • Stanford University
  • King Abdulaziz University
  • Umeå University
  • Jackson State University
  • Shanghai Jiao Tong University
  • University of Pittsburgh
  • German Center for Diabetes Research
  • Kuopio University Hospital
  • Netherlands Heart Institute
  • University Hospital of Lausanne
  • Oxford Centre for Diabetes, Endocrinology and Metabolism
  • University of Iceland
  • Universidade Federal de Pelotas
  • Fred Hutchinson Cancer Research Center
  • University of Southern California
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-08008-w

    DOI

    http://dx.doi.org/10.1038/s41467-018-08008-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111593700

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30670697


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