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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Kilpeläinen, Tuomas O; Bentley, Amy R; Noordam, Raymond; Sung, Yun Ju; Schwander, Karen; Winkler, Thomas W; Jakupovic, Hermina; Chasman, Daniel I; Manning, Alisa; Ntalla, Ioanna; Aschard, Hugues; Brown, Michael R; de Las Fuentes, Lisa; Franceschini, Nora; Guo, Xiuqing; Vojinovic, Dina; Aslibekyan, Stella; Feitosa, Mary F; Kho, Minjung; Musani, Solomon K; Richard, Melissa; Wang, Heming; Wang, Zhe; Bartz, Traci M; Bielak, Lawrence F; Campbell, Archie; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P; Horimoto, Andrea R V R; Li, Changwei; Lohman, Kurt K; Marten, Jonathan; Sim, Xueling; Smith, Albert V; Tajuddin, Salman M; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Evangelou, Evangelos; Gao, Chuan; Graff, Mariaelisa; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Jackson, Anne U; Zhao, Jing Hua.
Affiliation
  • Kilpeläinen TO; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. tuomas.kilpelainen@sund.ku.dk.
  • Bentley AR; Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA. tuomas.kilpelainen@sund.ku.dk.
  • Noordam R; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
  • Sung YJ; Internal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
  • Schwander K; Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
  • Winkler TW; Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
  • Jakupovic H; Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93051, Germany.
  • Chasman DI; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Manning A; Preventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
  • Ntalla I; Harvard Medical School, Boston, 02131, MA, USA.
  • Aschard H; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, 02114, MA, USA.
  • Brown MR; Department of Medicine, Harvard Medical School, Boston, 02115, MA, USA.
  • de Las Fuentes L; Clinical Pharmacology, William Harvey Research Instititute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Franceschini N; Department of Epidemiology, Harvard School of Public Health, Boston, 02115, MA, USA.
  • Guo X; Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75015, France.
  • Vojinovic D; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
  • Aslibekyan S; Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
  • Feitosa MF; Cardiovascular Division, Department of Medicine, Washington University, St. Louis, 63110, MO, USA.
  • Kho M; Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27514, NC, USA.
  • Musani SK; The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, 90502, CA, USA.
  • Richard M; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
  • Wang H; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, 35294, AL, USA.
  • Wang Z; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA.
  • Bartz TM; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Bielak LF; Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, 39213, MS, USA.
  • Campbell A; Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
  • Dorajoo R; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, USA.
  • Fisher V; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
  • Hartwig FP; Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, 98101, WA, USA.
  • Horimoto ARVR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Li C; Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Lohman KK; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
  • Marten J; Biostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
  • Sim X; Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, 96020220, RS, Brazil.
  • Smith AV; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.
  • Tajuddin SM; Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, 01246903, SP, Brazil.
  • Alver M; Epidemiology and Biostatistics, University of Giorgia at Athens College of Public Health, Athens, 30602, GA, USA.
  • Amini M; Public Health Sciences, Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, USA.
  • Boissel M; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Chai JF; Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
  • Chen X; Icelandic Heart Association, 201, Kopavogur, Iceland.
  • Divers J; Department of Biostatistics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Evangelou E; Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
  • Gao C; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Graff M; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
  • Harris SE; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
  • He M; Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
  • Hsu FC; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
  • Jackson AU; Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
  • Zhao JH; Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
Nat Commun ; 10(1): 376, 2019 01 22.
Article in En | MEDLINE | ID: mdl-30670697
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Exercise / Genetic Loci / Lipids Type of study: Prognostic_studies Limits: Aged80 Country/Region as subject: America do sul / Brasil Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Denmark Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Exercise / Genetic Loci / Lipids Type of study: Prognostic_studies Limits: Aged80 Country/Region as subject: America do sul / Brasil Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Denmark Country of publication: United kingdom