Journal article
Multi-ethnic genome-wide association study for atrial fibrillation
Nature genetics, Vol.50(9), pp.1225-+
09/01/2018
DOI: 10.1038/s41588-018-0133-9
PMCID: PMC6136836
PMID: 29892015
Abstract
Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
Details
- Title: Subtitle
- Multi-ethnic genome-wide association study for atrial fibrillation
- Creators
- Carolina Roselli - Broad InstituteMark D. Chaffin - Broad InstituteLu-Chen Weng - Broad InstituteStefanie Aeschbacher - University of BaselGustav Ahlberg - University of CopenhagenChristine M. Albert - Harvard UniversityPeter Almgren - Lund UniversityAlvaro Alonso - Emory UniversityChristopher D. Anderson - Broad InstituteKrishna G. Aragam - Broad InstituteDan E. Arking - Johns Hopkins UniversityJohn Barnard - Cleveland ClinicTraci M. Bartz - University of WashingtonEmelia J. Benjamin - Boston UniversityNathan A. Bihlmeyer - Johns Hopkins UniversityJoshua C. Bis - University of WashingtonHeather L. Bloom - Veterans Health AdministrationEric Boerwinkle - Baylor College of MedicineErwin B. Bottinger - Icahn School of Medicine at Mount SinaiJennifer A. Brody - University of WashingtonHugh Calkins - Johns Hopkins UniversityArchie Campbell - University of EdinburghThomas P. Cappola - University of PennsylvaniaJohn Carlquist - University of UtahDaniel I. Chasman - Broad InstituteLin Y. Chen - University of MinnesotaYii-Der Ida Chen - University of California, Los AngelesEue-Keun Choi - Seoul National UniversitySeung Hoan Choi - Broad InstituteIngrid E. Christophersen - Broad InstituteMina K. Chung - Cleveland ClinicJohn W. Cole - University of Maryland, BaltimoreDavid Conen - University of BaselJames Cook - University of LiverpoolHarry J. Crijns - Maastricht Univ, Med Ctr, Maastricht, NetherlandsMichael J. Cutler - Primary Children's HospitalScott M. Damrauer - University of PennsylvaniaBrian R. Daniels - Broad InstituteDawood Darbar - University of Illinois ChicagoGraciela Delgado - Heidelberg UniversityJoshua C. Denny - Vanderbilt UniversityMartin Dichgans - Ludwig-Maximilians-Universität MünchenMarcus Dörr - Univ Med Greifswald, Dept Internal Med B, Greifswald, GermanyElton A. Dudink - Maastricht Univ, Med Ctr, Maastricht, NetherlandsSamuel C. Dudley - University of MinnesotaNada Esa - University of Massachusetts Medical SchoolTonu Esko - University of TartuMarkku Eskola - Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, FinlandDiane Fatkin - Victor Chang Cardiac Research InstituteStephan B. Felix - Greifswald University HospitalIan Ford - University of GlasgowOscar H. Franco - Erasmus University RotterdamBastiaan Geelhoed - University of GroningenRaji P. Grewal - Seton Hall UniversityVilmundur Gudnason - University of IcelandXiuqing Guo - University of California, Los AngelesNamrata Gupta - Broad InstituteStefan Gustafsson - Uppsala UniversityRebecca Gutmann - University of IowaAnders Hamsten - Karolinska InstituteTamara B. Harris - National Institutes of HealthCaroline Hayward - University of EdinburghSusan R. Heckbert - University of WashingtonJussi Hernesniemi - Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, FinlandLynne J. Hocking - University of AberdeenAlbert Hofman - Erasmus University RotterdamAndrea R. V. R. Horimoto - Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, BrazilPaul L. Huang - Harvard UniversityJennifer Huffman - University of EdinburghErik Ingelsson - Stanford UniversityEsra Gucuk Ipek - Johns Hopkins UniversityKaoru Ito - RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, JapanJordi Jimenez-Conde - Autonomous University of BarcelonaRenee Johnson - Victor Chang Cardiac Research InstituteJ. Wouter Jukema - Leiden UniversityStefan Kaeaeb - Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, GermanyMika Kahonen - Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Dept Clin Physiol, Tampere, FinlandYoichiro Kamatani - RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, JapanJohn P. Kane - University of California, San FranciscoSekar Kathiresan - Broad InstituteAdnan Kastrati - Technical University of MunichPetra Katschnig-Winter - Medical University of GrazMaryam Kavousi - Erasmus University RotterdamThorsten Kessler - Technical University of MunichBas L. Kietselaer - Maastricht Univ, Med Ctr, Maastricht, NetherlandsPaulus Kirchhof - University of BirminghamMarcus E. Kleber - Heidelberg UniversityStacey Knight - University of UtahJose E. Krieger - Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, BrazilMichiaki Kubo - RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, JapanLenore J. Launer - National Institutes of HealthJari Laurikka - Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Heart Ctr,Dept Cardiothoracic Surg, Tampere, FinlandTerho Lehtimaki - Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, FinlandKirsten Leineweber - BayerRozenn N. Lemaitre - University of WashingtonMan Li - Johns Hopkins UniversityHong Euy Lim - Korea UniversityHenry J. Lin - University of California, Los AngelesHonghuang Lin - Boston UniversityLars Lind - Uppsala UniversityCecilia M. Lindgren - University of OxfordMarja-Liisa Lokki - University of HelsinkiBarry London - University of IowaRuth J. F. Loos - Icahn School of Medicine at Mount SinaiSiew-Kee Low - RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, JapanYingchang Lu - Icahn School of Medicine at Mount SinaiLeo-Pekka Lyytikainen - Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, FinlandPeter W. Macfarlane - University of GlasgowPatrik K. Magnusson - Karolinska InstituteAnubha Mahajan - University of OxfordRainer Malik - Ludwig-Maximilians-Universität MünchenAlfredo J. Mansur - Univ Sao Paulo, Heart Inst, Sao Paulo, BrazilGregory M. Marcus - University of California, Los AngelesLauren Margolin - Broad InstituteKenneth B. Margulies - University of PennsylvaniaWinfried Maerz - Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, AustriaDavid D. McManus - University of Massachusetts Chan Medical SchoolOlle Melander - Lund UniversitySanghamitra Mohanty - The University of Texas at AustinJay A Montgomery - Vanderbilt UniversityMichael P. Morley - University of PennsylvaniaAndrew P. Morris - University of LiverpoolMartina Mueller-Nurasyid - Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, GermanyAndrea Natale - The University of Texas at AustinSaman Nazarian - University of PennsylvaniaBenjamin Neumann - Ludwig-Maximilians-Universität MünchenChristopher Newton-Cheh - Broad InstituteMaartje N. Niemeijer - Erasmus University RotterdamKjell Nikus - Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, FinlandPeter Nilsson - Lund UniversityRaymond Noordam - Leiden UniversityHeidi Oellers - Atrial Fibrillat NETwork, Munster, GermanyMorten S. Olesen - University of CopenhagenMarju Orho-Melander - Lund UniversitySandosh Padmanabhan - Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, ScotlandHui-Nam Pak - Yonsei UniversityGuillaume Pare - McMaster UniversityNancy L. Pedersen - Karolinska InstituteJoanna Pera - Jagiellonian UniversityAlexandre Pereira - Harvard UniversityDavid Porteous - University of EdinburghBruce M. Psaty - University of WashingtonSara L. Pulit - University of OxfordClive R. Pullinger - University of California, San FranciscoDaniel J. Rader - University of PennsylvaniaLena Refsgaard - University of CopenhagenMarta Ribases - Autonomous University of BarcelonaPaul M. Ridker - Harvard UniversityMichiel Rienstra - University of GroningenLorenz Risch - University of BernDan M. Roden - Vanderbilt UniversityJonathan Rosand - Broad InstituteMichael A. Rosenberg - Harvard UniversityNatalia Rost - Broad InstituteJerome I. Rotter - University of California, Los AngelesSamir Saba - University of PittsburghRoopinder K. Sandhu - University of AlbertaRenate B. Schnabel - Universität HamburgKatharina Schramm - Ludwig-Maximilians-Universität MünchenHeribert Schunkert - Technical University of MunichClaudia Schurman - Icahn School of Medicine at Mount SinaiStuart A. Scott - Icahn School of Medicine at Mount SinaiIlkka Seppala - Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, FinlandChristian Shaffer - Vanderbilt UniversitySvati Shah - Duke UniversityAlaa A. Shalaby - University of PittsburghJaemin Shim - Korea UniversityM. Benjamin Shoemaker - Vanderbilt UniversityJoylene E. Siland - University of GroningenJuha Sinisalo - University of HelsinkiMoritz F. Sinner - Ludwig-Maximilians-Universität MünchenAgnieszka Slowik - Jagiellonian UniversityAlbert V. Smith - University of IcelandBlair H. Smith - University of DundeeJ. Gustav Smith - Broad InstituteJonathan D. Smith - Cleveland ClinicNicholas L. Smith - Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USAElsayed Z. Soliman - Wake Forest UniversityNona Sotoodehnia - University of WashingtonBruno H. Stricker - Erasmus University RotterdamAlbert Sun - Duke UniversityHan Sun - Cleveland ClinicJesper H. Svendsen - University of CopenhagenToshihiro Tanaka - Tokyo Medical and Dental UniversityKahraman Tanriverdi - University of Massachusetts Medical SchoolKent D. Taylor - University of California, Los AngelesMaris Teder-Laving - University of TartuAlexander Teumer - Universitätsmedizin GreifswaldSebastien Theriault - McMaster UniversityStella Trompet - Leiden UniversityNathan R. Tucker - Broad InstituteArnljot Tveit - University of OsloAndre G. Uitterlinden - Erasmus University RotterdamPim Van Der Harst - University of GroningenIsabelle C. Van Gelder - University of GroningenDavid R. Van Wagoner - Cleveland ClinicNiek Verweij - University of GroningenEfthymia Vlachopoulou - University of HelsinkiUwe Voelker - Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, GermanyBiqi Wang - Boston UniversityPeter E. Weeke - University of CopenhagenBob Weijs - Maastricht UniversityRaul Weiss - The Ohio State UniversityStefan Weiss - University of GreifswaldQuinn S. Wells - Vanderbilt UniversityKerri L. Wiggins - University of WashingtonJorge A. Wong - McMaster UniversityDaniel Woo - University of CincinnatiBradford B. Worrall - University of VirginiaPil-Sung Yang - Yonsei UniversityJie Yao - University of California, Los AngelesZachary T. Yoneda - Vanderbilt UniversityTanja Zeller - Universität HamburgLingyao Zeng - Technical University of MunichSteven A. Lubitz - Broad InstituteKathryn L. Lunetta - Boston UniversityPatrick T. Ellinor - Broad Institute
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.50(9), pp.1225-+
- DOI
- 10.1038/s41588-018-0133-9
- PMID
- 29892015
- PMCID
- PMC6136836
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 12
- Grant note
- 16EIA26410001 / American Heart Association-American Stroke Association; American Heart Association U01 HG007417 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01 HL138737; R01 HL116747; R01 HL128914; R01 HL111314; K23 HL127296; R01 HL090620; U01 HL120393; U01 HL130114; R01 HL120393; R01 HL139731; L30 HL123413; R01 HL105756; R01 HL092577; R01 HL092217; K24 HL105780 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) MC_PC_17228; MC_QA137853 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission T32GM007569 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) ZIAAG007380 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) T32 GM007569 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 2014105 / Doris Duke Charitable Foundation; Doris Duke Charitable Foundation (DDCF) U01HL130114 / 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) U01HG007417 / 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)
- Language
- English
- Date published
- 09/01/2018
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984297505602771
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