Evidence map›Paper›PMID 37532724›Full record

SynthesisNature communications2023

Genetic insights into resting heart rate and its role in cardiovascular disease.

Yordi J van de Vegte, Ruben N Eppinga, M Yldau van der Ende, Yanick P Hagemeijer, Yuvaraj Mahendran, Elias Salfati, Albert V Smith, Vanessa Y Tan, Dan E Arking, Ioanna Ntalla and 181 more

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 3 pooled it
6.6field-weighted citation impact, top 2% 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

18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 30 citations in OpenAlex.

  1. Pooled it
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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

191 authors at 20 institutions in 19 countries.

Yordi J van de Vegte *Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, the Netherlands.ORCID http://orcid.org/0000-0002-6689-0144
Ruben N Eppinga *Department of Cardiology, Isala Zwolle ziekenhuis, Zwolle, 8025 AB, the Netherlands.
M Yldau van der EndeDepartment of Cardiology, University medical Center Utrecht, Utrecht, 3584 Cx, the Netherlands.
Yanick P HagemeijerDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, the Netherlands.ORCID http://orcid.org/0000-0001-6036-3741
Yuvaraj MahendranThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen, Copenhagen Ø, 2100, Denmark.
Elias SalfatiDepartment of Medicine, Stanford University School of Medicine, Stanford, 94305, USA.
Albert V SmithDepartment of Biostatistics, University of Michigan, Ann Arbor, MI48109, USA.ORCID http://orcid.org/0000-0003-1942-5845
Vanessa Y TanBristol Medical School, Population Health Sciences, University of Bristol, Bristol, BS82BN, UK.
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21215, USA.
Ioanna NtallaClinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Emil V AppelThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen, Copenhagen Ø, 2100, Denmark.
Claudia SchurmannThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, 10029, USA.ORCID http://orcid.org/0000-0003-4158-9192
Jennifer A BrodyMedicine, University of Washington, Seattle, 98195, USA.ORCID http://orcid.org/0000-0001-8509-148X
Rico RueediDepartment of Computational Biology, University of Lausanne, Lausanne, 1015, Switzerland.
Ozren PolasekDepartment of Public Health, University of Split School of Medicine, Split, 21000, Croatia.
Gardar SveinbjornssondeCODE genetics / Amgen Inc., Reykjavik, 102, Iceland.ORCID http://orcid.org/0000-0003-2429-9468
Cecile LecoeurUMR 8199, University of Lille Nord de France, Lille, 59000, France.ORCID http://orcid.org/0000-0003-0075-6417
Claes LadenvallClinial Genomics Uppsala, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, 75185, Sweden.ORCID http://orcid.org/0000-0002-7501-6598
Jing Hua ZhaoBHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, CB2 0BB, UK.
Aaron IsaacsCARIM School for Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio), Department of Physiology, Maastricht University, Maastricht, 6229ER, Netherlands.ORCID http://orcid.org/0000-0001-5037-4834
Lihua WangDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63108-2212, Campus Box 8506, USA.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0003-3137-6337
Shih-Jen HwangDivision of Intramural Research, National Heart Lung and Blood Institute, NIH, USA, Framingham, 1702, USA.
Nina MononenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, FI-33014, Finland.
Kirsi AuroDepartment of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland, Helsinki, FI-00290, Finland.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-9672-2547
Lawrence F BielakDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-3443-8030
Linyao ZengDepartment of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, 80636, Germany.
Nabi ShahDivision of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
Maria NethanderSahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.ORCID http://orcid.org/0000-0003-3688-906X
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Tuomo RankinenHuman Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.
Sonali PechlivanisInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, 45122, Germany.
Lu QiDepartment of Epidemiology, Tulane University, New Orleans, LA, 70112, USA.
Wei ZhaoDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0001-7388-0692
Federica RizziUnit of Biomedicine, Bio4Dreams-Business Nursery for Life Sciences, Milano, 20121, Italy.
Toshiko TanakaLongitudinal Study Section, National Institute on Aging, Baltimore, 21224, USA.
Antonietta RobinoInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
Massimiliano CoccaInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
Leslie LangeMedicine, University of Colorado Anschutz Medical Campus, Aurora, 80045, USA.
Martina Müller-NurasyidIBE, Ludwig-Maximilians-University Munich, LMU Munich, Munich, 81377, Germany.
Carolina RoselliInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, 85764, Germany.ORCID http://orcid.org/0000-0001-5267-6756
Weihua ZhangDepartment of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.ORCID http://orcid.org/0000-0001-8279-3611
Marcus E KleberVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68167, Germany.ORCID http://orcid.org/0000-0003-0663-7275
Xiuqing GuoPediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, Torrance, 90502, USA.
Henry J LinPediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, Torrance, 90502, USA.
Francesca PavaniInstitute for Biomedicine, Eurac Research, Bolzano, 39100, Italy.
Tessel E GaleslootRadboud university medical center, Nijmegen, 6500 HB, the Netherlands.
Raymond NoordamDepartment of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands.ORCID http://orcid.org/0000-0001-7801-809X
Yuri MilaneschiDepartment of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Amsterdam UMC, Vrije Universiteit, Amsterdam, Amsterdam, 1081 HL, the Netherlands.
Katharina E SchrautCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, Scotland, UK.
Marcel den HoedThe Beijer laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and Science for Life Laboratory, Uppsala, 75237, Sweden.
Frauke DegenhardtInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany.
Stella TrompetDepartment of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands.ORCID http://orcid.org/0000-0001-5006-0528
Marten E van den BergDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, 3015GD, the Netherlands.
Giorgio PistisInstitute of Genetics and Biomedic Research (IRGB), Italian National Research Council (CNR), Monserrato, (CA), 9042, Italy.
Yih-Chung ThamSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Stefan WeissInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.ORCID http://orcid.org/0000-0002-3553-4315
Xueling S SimSaw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.ORCID http://orcid.org/0000-0002-1233-7642
Hengtong L LiSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.ORCID http://orcid.org/0000-0001-8450-3518
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.ORCID http://orcid.org/0000-0001-5047-4077
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, FI-33014, Finland.ORCID http://orcid.org/0000-0002-7200-5455
M Abdullah SaidDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, the Netherlands.ORCID http://orcid.org/0000-0003-2920-7745
Daniel R WitteDepartment of Public Health, Aarhus University, Aarhus C, 8000, Denmark.
Carlos IribarrenDivision of Research, Kaiser Permenente of Northern California, Oakland, 94612, USA.
Lenore LaunerNational Institute on Aging, Bethesda, MSC2292, USA.ORCID http://orcid.org/0000-0002-3238-7612
Susan M RingBristol Medical School, Population Health Sciences, University of Bristol, Bristol, BS82BN, UK.ORCID http://orcid.org/0000-0003-3103-9330
Paul S de VriesDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, School of Public Health, Houston, 77030, USA.
Peter SeverNational Heart and Lung Institute, Imperial College London, London, W12 0NN, UK.
Allan LinnebergCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, 2400, Denmark.ORCID http://orcid.org/0000-0002-0994-0184
Erwin P BottingerThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Bruce M PsatyDepartments of Medicine, Epidemiology and Health Systems and Population Health, University of Washington, Seattle, 98195, USA.ORCID http://orcid.org/0000-0002-7278-2190
Nona SotoodehniaMedicine and Epidemiology, University of Washington, Seattle, 98195, USA.
Ivana KolcicDepartment of Public Health, University of Split School of Medicine, Split, 21000, Croatia.
DCCT/EDIC Research Group
David O ArnardeCODE genetics / Amgen Inc., Reykjavik, 102, Iceland.
Daniel F GudbjartssondeCODE genetics / Amgen Inc., Reykjavik, 102, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Hilma HolmdeCODE genetics / Amgen Inc., Reykjavik, 102, Iceland.ORCID http://orcid.org/0000-0002-9517-6636
Beverley BalkauCentre for Research in Epidemiology and Population Health, Institut national de la santé et de la recherche médicale, Villejuif, 94800, France.ORCID http://orcid.org/0000-0003-2021-413X
Claudia T SilvaGenetic Epidemiology Unit, Dept. of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000CA, Netherlands.
Christopher H Newton-ChehCardiology Section, Massachusetts general hospital,, Boston, 02130, USA.ORCID http://orcid.org/0000-0002-3001-9111
Kjell NikusDepartment of Cardiology, Heart Center, Tampere University Hospital, Tampere, FI-33521, Finland.
Perttu SaloDepartment of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland, Helsinki, FI-00290, Finland.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Patricia A PeyserDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-9717-8459
Heribert SchunkertDepartment of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, 80636, Germany.ORCID http://orcid.org/0000-0001-6428-3001
Mattias LorentzonSahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.
Jari LahtiDepartment of Psychology and Logopedics, University of Helsinki, Helsinki, 00014, Finland.ORCID http://orcid.org/0000-0002-4310-5297
Dabeeru C RaoDivision of Biostatistics, Washington University, St. Louis, MO, 63110, USA.
Marilyn C CornelisPreventive Medicine, Northwestern University, Chicago, IL, 60611, USA.
Jessica D FaulSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
Jennifer A SmithDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-3575-5468
Katarzyna Stolarz-SkrzypekDepartment of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Kraków, 31-008, Poland.
Stefania BandinelliGeriatric Unit, Unità sanitaria locale Toscana Centro, Florence, 50142, Italy.
Maria Pina ConcasInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, 34137, Italy.ORCID http://orcid.org/0000-0003-3598-2537
Gianfranco SinagraCardiovascular Department, "Ospedali Riuniti and University of Trieste", Trieste, 34149, Italy.
Thomas MeitingerInstitute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, München, 81675, Germany.ORCID http://orcid.org/0000-0002-8838-8403
Melanie WaldenbergerResearch Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, 85764, Germany.ORCID http://orcid.org/0000-0003-0583-5093
Moritz F SinnerGerman Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, 80802, Germany.ORCID http://orcid.org/0000-0002-6660-796X
Konstantin StrauchInstitute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, 55101, Germany.
Graciela E DelgadoVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68167, Germany.
Kent D TaylorPediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, Torrance, 90502, USA.ORCID http://orcid.org/0000-0002-2756-4370
Jie YaoPediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, Torrance, 90502, USA.
Luisa FocoInstitute for Biomedicine, Eurac Research, Bolzano, 39100, Italy.ORCID http://orcid.org/0000-0002-6694-3322
Olle MelanderDepartment of Internal Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Malmo, 221 85, Sweden.
Jacqueline de GraafRadboud university medical center, Nijmegen, 6500 HB, the Netherlands.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands.
Eco J C de GeusBiological Psychology, EMGO+ Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University, Amsterdam, 1081 BT, the Netherlands.
Åsa JohanssonDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 75108, Sweden.ORCID http://orcid.org/0000-0002-2915-4498
Peter K JoshiCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, Scotland, UK.ORCID http://orcid.org/0000-0002-6361-5059
Lars LindDepartment of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital, Uppsala, 75237, Sweden.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany.
Peter W MacfarlaneInstitute of Health and Wellbeing, Faculty of Medicine, University of Glasgow, Glasgow, G12 0XH, UK.ORCID http://orcid.org/0000-0002-5390-1596
Kirill V TarasovLaboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.ORCID http://orcid.org/0000-0001-7799-4670
Nicholas TanSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Stephan B FelixDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, 17475, Germany.
E-Shyong TaiSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Debra Q QuekSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.ORCID http://orcid.org/0000-0003-1949-2298
Johan OrmelDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.ORCID http://orcid.org/0000-0002-5463-037X
Martin IngelssonDepartment of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, 75237, Sweden.
Cecilia LindgrenGenetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Andrew P MorrisGenetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0002-6805-6014
Olli T RaitakariCentre for Population Health Research, University of Turku and Turku University Hospital, Turku, FI-20521, Finland.
Torben HansenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen, Copenhagen Ø, 2100, Denmark.ORCID http://orcid.org/0000-0001-8748-3831
Themistocles AssimesDepartment of Medicine, Stanford University School of Medicine, Stanford, 94305, USA.ORCID http://orcid.org/0000-0003-2349-0009
Vilmundur GudnasonFaculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.ORCID http://orcid.org/0000-0001-5696-0084
Nicholas J TimpsonMRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.ORCID http://orcid.org/0000-0002-7141-9189
Alanna C MorrisonDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, School of Public Health, Houston, 77030, USA.ORCID http://orcid.org/0000-0001-6381-4296
Patricia B MunroeClinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-4176-2947
David P StrachanPopulation Health Research Institute, St George's, University of London, London, SW17 0RE, UK.ORCID http://orcid.org/0000-0001-7854-1366
Niels GrarupThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen, Copenhagen Ø, 2100, Denmark.ORCID http://orcid.org/0000-0001-5526-1070
Ruth J F LoosThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen, Copenhagen Ø, 2100, Denmark.ORCID http://orcid.org/0000-0002-8532-5087
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, 98195, USA.ORCID http://orcid.org/0000-0002-7100-512X
Peter VollenweiderDepartment of Medicine, Internal Medicine, Lausanne University hospital, Lausanne, 1015, Switzerland.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, Scotland, UK.
Kari StefanssondeCODE genetics / Amgen Inc., Reykjavik, 102, Iceland.
Philippe FroguelDepartment of Metabolism, Imperial College London, London, W12 0HS, UK.ORCID http://orcid.org/0000-0003-2972-0784
Leif GroopLund University Diabetes Center, Department of Clinical Sciences, Lund University, Malmö, 20502, Sweden.ORCID http://orcid.org/0000-0002-0187-3263
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0003-1422-2993
Cornelia M van DuijnGenetic Epidemiology Unit, Dept. of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000CA, Netherlands.
Mary F FeitosaDivision of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63108-2212, Campus Box 8506, USA.ORCID http://orcid.org/0000-0002-0933-2410
Christopher J O'DonnellCardiology Section, VA Boston Healthcare System, Harvard Medical School, Boston, MA, 02132, USA.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, Tampere, FI-33521, Finland.
Markus PerolaDepartment of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland, Helsinki, FI-00290, Finland.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0002-6442-7754
Sharon L R KardiaDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Jeanette ErdmannInstitute for Cardiogenetics, University of Lübeck, Lübeck, 23562, Germany.ORCID http://orcid.org/0000-0002-4486-6231
Colin N A PalmerDivision of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.ORCID http://orcid.org/0000-0002-6415-6560
Claes OhlssonSahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden.ORCID http://orcid.org/0000-0002-9633-2805
David J PorteousCentre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID http://orcid.org/0000-0003-1249-6106
Johan G ErikssonDepartment of General practice and primary care, University of Helsinki, Helsinki, 00014, Finland.
Claude BouchardHuman Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.ORCID http://orcid.org/0000-0002-0048-491X
Susanne MoebusInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, 45122, Germany.ORCID http://orcid.org/0000-0002-0072-5410
Peter KraftEpidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02112, USA.ORCID http://orcid.org/0000-0002-4472-8103
David R WeirSurvey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.ORCID http://orcid.org/0000-0002-1661-2402
Daniele CusiUnit of Biomedicine, Bio4Dreams-Business Nursery for Life Sciences, Milano, 20121, Italy.
Luigi FerrucciLongitudinal Study Section, National Institute on Aging, Baltimore, 21224, USA.ORCID http://orcid.org/0000-0002-6273-1613
Sheila UliviInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
Giorgia GirottoInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, 34137, Italy.ORCID http://orcid.org/0000-0003-4507-6589
Adolfo CorreaJackson Heart Study, University of Mississippi Medical Center, Jackson, 39216, USA.ORCID http://orcid.org/0000-0002-9501-600X
Stefan KääbGerman Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, 80802, Germany.ORCID http://orcid.org/0000-0001-8824-3581
Annette PetersInstitute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, 85764, Germany.ORCID http://orcid.org/0000-0001-6645-0985
John C ChambersDepartment of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
Jaspal S KoonerDepartment of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, Middlesex, UB1 3HW, UK.ORCID http://orcid.org/0000-0003-2086-4837
Winfried MärzVth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68167, Germany.
Jerome I RotterPediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA, Torrance, 90502, USA.ORCID http://orcid.org/0000-0001-7191-1723
Andrew A HicksInstitute for Biomedicine, Eurac Research, Bolzano, 39100, Italy.ORCID http://orcid.org/0000-0001-6320-0411
J Gustav SmithDepartment of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, 221 85, Sweden.
Lambertus A L M KiemeneyRadboud university medical center, Nijmegen, 6500 HB, the Netherlands.ORCID http://orcid.org/0000-0002-2368-1326
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Amsterdam UMC, Vrije Universiteit, Amsterdam, Amsterdam, 1081 HL, the Netherlands.
Ulf GyllenstenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 75108, Sweden.ORCID http://orcid.org/0000-0002-6316-3355
James F WilsonCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, Scotland, UK.ORCID http://orcid.org/0000-0001-5751-9178
Stephen BurgessMRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK.ORCID http://orcid.org/0000-0001-5365-8760
Johan SundströmDepartment of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital, Uppsala, 75237, Sweden.ORCID http://orcid.org/0000-0003-2247-8454
Wolfgang LiebInstitute of Epidemiology and Biobank PopGen, Kiel University, Kiel, 24105, Germany.ORCID http://orcid.org/0000-0003-2544-4460
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, ZA, 2333, the Netherlands.ORCID http://orcid.org/0000-0002-3246-8359
Mark EijgelsheimDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, 3015GD, the Netherlands.
Edward L M LakattaLaboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.ORCID http://orcid.org/0000-0002-4772-0035
Ching-Yu ChengSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.ORCID http://orcid.org/0000-0003-0655-885X
Marcus DörrDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, 17475, Germany.ORCID http://orcid.org/0000-0001-7471-475X
Tien-Yin WongSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
Charumathi SabanayagamSingapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.ORCID http://orcid.org/0000-0002-4042-4719
Albertine J OldehinkelInterdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.ORCID http://orcid.org/0000-0003-3925-3913
Harriette RieseDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, FI-33014, Finland.ORCID http://orcid.org/0000-0002-2555-4427
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, the Netherlands.
Pim van der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, the Netherlands. P.vanderHarst@umcutrecht.nl.
University Medical Center Groningen · NLUniversity of Michigan · USSingapore National Eye Center · SGUniversity of Copenhagen · DKUniversity of Helsinki · FIdeCODE Genetics (Iceland) · ISLeiden University Medical Center · NLThe Lundquist Institute · USUppsala University · SEIRCCS Materno Infantile Burlo Garofolo · ITUniversity of Cambridge · GBUniversity of Washington · USChristian-Albrechts-Universität zu Kiel · DEErasmus MC · NLEurac Research · ITLund University · SENational Institute on Aging · USNational University of Singapore · SGRadboud University Nijmegen · NLTampere University · FI

Funding

Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7M
CLINICAL PROJECT: Age, Gene/Environment Susceptibility Study on the Multi-omics of Aging: A clinical epidemiologic prospective studyZIAAG007380 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$6.1M
The InChianti StudyZIAAG001050 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$2.1M
Genome-wide Association Study of Cardiovascular Traits in 6142 SardiniansZIAAG000799 · NIA · NATIONAL INSTITUTE ON AGING · PI LAKATTA, EDWARD · 2009 to 2025
$1.8M
Cancer Research UK C18281/A29019Medical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MC_PC_U127592696Medical Research Council MC_UU_00002/7Medical Research Council MC_UU_00006/1Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00032/1Medical Research Council MR/R010676/1NHLBI NIH HHS R01 HL105756NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193Wellcome Trust 100114Wellcome Trust 202802/Z/16/ZWellcome Trust 204623/Z/16/ZWellcome Trust 212945/Z/18/ZWellcome Trust 217065/Z/19/Z
6 · The paper itself

Abstract

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Indexed as

Atrial FibrillationCardiovascular DiseasesGenetic Predisposition to DiseaseGenome-Wide Association StudyHeart RateHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk Factors

Identifiers

PMID37532724
PMCPMC10397318
OpenAlexW4385490353

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