Evidence map›Paper›PMID 30670697›Full record

ArticleNature communications2019

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

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 and 220 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 11 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 11 syntheses or guidelines pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  3. Selected social and lifestyle correlates of brain health markers: the Cross-Cohort Collaboration Consortium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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  15. Robust Mixed Model Association Test for Gene-Environment Interactions.medRxiv : the preprint server for health sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

230 authors at 20 institutions in 24 countries.

Tuomas O KilpeläinenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. tuomas.kilpelainen@sund.ku.dk.
Amy R BentleyCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.ORCID http://orcid.org/0000-0002-0827-9101
Raymond NoordamInternal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Yun Ju SungDivision of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
Karen SchwanderDivision of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
Thomas W WinklerDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, 93051, Germany.
Hermina JakupovićNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.ORCID http://orcid.org/0000-0001-9667-9406
Daniel I ChasmanPreventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
Alisa ManningClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, 02114, MA, USA.ORCID http://orcid.org/0000-0003-0247-902X
Ioanna NtallaClinical Pharmacology, William Harvey Research Instititute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Hugues AschardDepartment of Epidemiology, Harvard School of Public Health, Boston, 02115, MA, USA.ORCID http://orcid.org/0000-0003-0907-2548
Michael R BrownHuman 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.
Lisa de las FuentesDivision of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.ORCID http://orcid.org/0000-0002-4689-325X
Nora FranceschiniEpidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27514, NC, USA.
Xiuqing GuoThe 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.
Dina VojinovicDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Stella AslibekyanDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, 35294, AL, USA.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA.
Minjung KhoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Solomon K MusaniJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, 39213, MS, USA.
Melissa RichardInstitute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.ORCID http://orcid.org/0000-0003-0129-9860
Heming WangDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, USA.
Zhe WangHuman 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.
Traci M BartzCardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, 98101, WA, USA.
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Archie CampbellCentre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Rajkumar DorajooGenome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
Virginia FisherBiostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
Fernando P HartwigPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, 96020220, RS, Brazil.
Andrea R V R HorimotoLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, 01246903, SP, Brazil.
Changwei LiEpidemiology and Biostatistics, University of Giorgia at Athens College of Public Health, Athens, 30602, GA, USA.
Kurt K LohmanPublic Health Sciences, Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, USA.
Jonathan MartenMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Xueling SimSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Albert V SmithIcelandic Heart Association, 201, Kopavogur, Iceland.
Salman M TajuddinHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
Maris AlverEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Marzyeh AminiDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
Mathilde BoisselCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
Jin Fang ChaiSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Xu ChenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
Jasmin DiversDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
Chuan GaoMolecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Mariaelisa GraffEpidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27514, NC, USA.
Sarah E HarrisCentre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Meian HeDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
Fang-Chi HsuDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
Jing Hua ZhaoMRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
Aldi T KrajaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA.
Brigitte KühnelResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Federica LaguzziUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
Rainer RauramaaFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
Muhammad RiazCollege of Medicine, Biological Sciences and Psychology, Health Sciences, The Infant Mortality and Morbidity Studies (TIMMS), Leicester, LE1 7RH, UK.
Antonietta RobinoInstitute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
Rico RueediDepartment of Computational Biology, University of Lausanne, Lausanne, 1015, Switzerland.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
Fumihiko TakeuchiDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 1628655, Japan.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
Tibor V VargaDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, 20502, Sweden.
Niek VerweijUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700 RB, The Netherlands.
Erin B WareSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48104, MI, USA.
Wanqing WenDivision of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37203, TN, USA.
Xiaoyin LiDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106, OH, USA.
Lisa R YanekDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Najaf AminDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Donna K ArnettDean's Office, University of Kentucky College of Public Health, Lexington, 40536, KY, USA.
Eric BoerwinkleHuman 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.
Marco BrumatDepartment of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
Brian CadeDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, USA.
Mickaël CanouilCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
Yii-Der Ida ChenThe 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.
Maria Pina ConcasInstitute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
John ConnellNinewells Hospital & Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
Renée de MutsertClinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, Netherlands.
H Janaka de SilvaDepartment of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, 11600, Sri Lanka.
Paul S de VriesHuman 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.
Ayşe DemirkanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Jingzhong DingDepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Charles B EatonDepartment of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, 02860, RI, USA.
Jessica D FaulSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48104, MI, USA.
Yechiel FriedlanderBraun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel.
Kelley P GabrielDepartment of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Austin, Austin, 78712, TX, USA.
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Franco GiulianiniPreventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
Chi Charles GuDivision of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
Dongfeng GuDepartment of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100006, China.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
Jiang HeEpidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, 70112, LA, USA.
Sami HeikkinenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, 70211, Finland.
Chew-Kiat HengDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
Steven C HuntDivision of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, 84132, UT, USA.
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Jost B JonasDepartment of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, 68167, Germany.
Woon-Puay KohSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Pirjo KomulainenFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
Jose E KriegerLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, 01246903, SP, Brazil.
Stephen B KritchevskyDepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Zoltán KutalikSwiss Institute of Bioinformatics, 1015, Lausanne, Switzerland.
Johanna KuusistoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
Carl D LangefeldDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
Karin LeanderUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
Rozenn N LemaitreCardiovascular Health Research Unit, Medicine, University of Washington, Seattle, 98101, WA, USA.
Cora E LewisDivision of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, School of Medicine, Birmingham, 35294, AL, USA.
Jingjing LiangDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106, OH, USA.
Lifelines Cohort Study
Jianjun LiuGenome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
Reedik MägiEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, 22908, VA, USA.
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Yuri MilaneschiDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 HV, The Netherlands.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, 27514, NC, USA.
Thomas H MosleyGeriatrics, Medicine, University of Mississippi, Jackson, 39216, MS, USA.
Alison D MurrayThe Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Mike A NallsMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, 20892, MD, USA.
Ei-Ei Khaing NangSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9PQ, UK.
Sotoodehnia NonaCardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, 98101, WA, USA.
Jill M NorrisDepartment of Epidemiology, University of Colorado Denver, Aurora, 80045, CO, USA.
Chiamaka Vivian NwubaNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
Jeff O'ConnellDivision of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, 21201, MD, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
George J PapanicolauEpidemiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
Raha PazokiDepartment of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Ozren PolasekDepartment of Public Health, Department of Medicine, University of Split, Split, 21000, Croatia.
David J PorteousCentre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Alaitz PovedaDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, 20502, Sweden.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland.
Stephen S RichCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, 22908, VA, USA.
Neil RischInstitute for Human Genetics, Department of Epidemiology and Biostatistics, University of California, San Francisco, 94143, CA, USA.
Jennifer G RobinsonDepartment of Epidemiology and Medicine, University of Iowa, Iowa City, 52242, IA, USA.
Lynda M RosePreventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
Igor RudanCentre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK.
Pamela J SchreinerDivision of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, 55454, MN, USA.
Robert A ScottMRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
Stephen S SidneyKaiser Permanente Washington, Health Research Institute, Seattle, 98101, WA, USA.
Mario SimsJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, 39213, MS, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
Tamar SoferDepartment of Medicine, Harvard Medical School, Boston, 02115, MA, USA.
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Barbara SternfeldKaiser Permanente Washington, Health Research Institute, Seattle, 98101, WA, USA.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Hua TangDepartment of Genetics, Stanford University, Stanford, 94305, CA, USA.
Kent D TaylorThe 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.
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, 55455, MN, USA.
Jaakko TuomilehtoPublic Health Solutions, National Institute for Health and Welfare, Helsinki, 00271, Finland.
André G UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
M Yldau van der EndeUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700 RB, The Netherlands.
Diana van HeemstInternal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
Trudy VoortmanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Melanie WaldenbergerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Patrik WennbergDepartment of Public Health & Clinical Medicine, Umeå University, Umeå, 90185, Västerbotten, Sweden.
Gregory WilsonJackson Heart Study, School of Public Health, Jackson State University, Jackson, 39213, MS, USA.
Yong-Bing XiangState Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.
Jie YaoThe 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.
Caizheng YuDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
Jian-Min YuanDepartment of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, 15261, PA, USA.
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Alan B ZondermanBehavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
Diane M BeckerDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Ulf de FaireUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Paul ElliottDepartment of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Barry I FreedmanSection on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Philippe FroguelCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
Paolo GaspariniInstitute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
Norihiro KatoDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 1628655, Japan.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
Timo A LakkaFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
Albertine J OldehinkelDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 HV, The Netherlands.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9PQ, UK.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37203, TN, USA.
Pim van der HarstUniversity of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700 RB, The Netherlands.
Jana V Van Vliet-OstaptchoukDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Peter VollenweiderInternal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, 1011, Switzerland.
Lynne E WagenknechtPublic Health Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
Ya X WangBeijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
David R WeirSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48104, MI, USA.
Tangchun WuDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37203, TN, USA.
Xiaofeng ZhuDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106, OH, USA.
Michele K EvansHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
Paul W FranksDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, 20502, Sweden.
Vilmundur GudnasonIcelandic Heart Association, 201, Kopavogur, Iceland.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Bernardo L HortaPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, 96020220, RS, Brazil.
Tanika N KellyEpidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, 70112, LA, USA.
Yongmei LiuPublic Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, USA.
Kari E NorthEpidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27514, NC, USA.
Alexandre C PereiraLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, 01246903, SP, Brazil.
Paul M RidkerPreventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
E Shyong TaiSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Rob M van DamSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
Ervin R FoxCardiology, Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
Ching-Ti LiuBiostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.ORCID http://orcid.org/0000-0002-0703-0742
Dennis O Mook-KanamoriClinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, Netherlands.
Michael A ProvinceDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA.
Susan RedlineDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, USA.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
Jerome I RotterThe 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.
Charles B KooperbergFred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, 98109, WA, USA.
W James GaudermanBiostatistics, Preventive Medicine, University of Southern California, Los Angeles, 90032, CA, USA.
Bruce M PsatyKaiser Permanente Washington, Health Research Institute, Seattle, 98101, WA, USA.
Kenneth RiceDepartment of Biostatistics, University of Washington, Seattle, 98105, WA, USA.ORCID http://orcid.org/0000-0002-3071-7278
Patricia B MunroeClinical Pharmacology, William Harvey Research Instititute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-4176-2947
Myriam FornageInstitute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
L Adrienne CupplesBiostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
Charles N RotimiCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
Alanna C MorrisonHuman 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.
Dabeeru C RaoDivision of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA. rao@wustl.edu.
Ruth J F LoosIcahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, 10029, NY, USA. ruth.loos@mssm.edu.ORCID http://orcid.org/0000-0002-8532-5087
University Medical Center Groningen · NLUniversity of Michigan · USBrigham and Women's Hospital · USNational Institutes of Health · USWake Forest University · USNational University of Singapore · SGThe University of Texas Health Science Center at Houston · USKaiser Permanente Washington Health Research Institute · USThe Lundquist Institute · USUniversity of North Carolina at Chapel Hill · USBoston University · USErasmus MC · NLUniversity of Eastern Finland · FIUniversity of Washington · USWashington University in St. Louis · USCentre National de la Recherche Scientifique · FRHarvard University · USLeiden University Medical Center · NLUniversity of Cambridge · GBUniversity of Minnesota · US

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
Healthy Aging In Neighborhoods of Diversity Across the Life Span (HANDLS)ZIAAG000513 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2009 to 2025
$70.9M
Genetic epidemiology of complex diseasesZIAHG200362 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ROTIMI, CHARLES · 2009 to 2025
$54.7M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul Marjoram · 2016 to 2026
$25.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Zevalin Radioimmunotherapy Using a Modified TreatmentM01RR000032 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI RICH, ROBERT R. · 1985 to 2008
$23.6M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
The Underlying Biology of Health DisparitiesZIAAG000519 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2009 to 2025
$15.7M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
Identifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6M
Biotechnology and Biological Sciences Research Council BB/F019394/1Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_12015/1Medical Research Council MR/K026992/1Medical Research Council MR/L01341X/1Medical Research Council MR/L01632X/1Medical Research Council MR/R023484/1NCI NIH HHS P01 CA196569NCI NIH HHS R01 CA080205NCI NIH HHS R01 CA144034NCI NIH HHS UM1 CA173640NCI NIH HHS UM1 CA182876NCI NIH HHS UM1 CA182910NCRR NIH HHS M01 RR000032NHGRI NIH HHS U01 HG007417NHLBI NIH HHS K01 HL135405NHLBI NIH HHS K01 HL136700NHLBI NIH HHS R01 HL046380NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL118305NHLBI NIH HHS R01 HL119443NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL142302NHLBI NIH HHS R35 HL135818NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL137162NIA NIH HHS R01 AG055406NIA NIH HHS U01 AG009740NICHD NIH HHS P2C HD050924NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30 DK079626NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK075787NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R01 DK107786NIDDK NIH HHS T32 DK091317NIDDK NIH HHS U01 DK062370
6 · The paper itself

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.

Indexed as

ExerciseAdolescentAdultAgedAged, 80 and overAsian PeopleBlack PeopleBrazilCalcium-Binding ProteinsCholesterolCholesterol, HDLCholesterol, LDLFemaleGenetic LociGenome-Wide Association StudyGenotypeCalcium-Binding ProteinsCholesterolCholesterol, HDLCholesterol, LDLCLASP1 protein, humanCNTNAP2 protein, humanLHX1 protein, humanLIM-Homeodomain ProteinsLipidsMembrane ProteinsMicrotubule-Associated ProteinsMuscle ProteinsNerve Tissue Proteinssyntrophin alpha1Transcription FactorsTriglycerides

Identifiers

PMID30670697
PMCPMC6342931
OpenAlexW2911684552

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