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Multi-ethnic genome-wide association study for atrial fibrillation.


ABSTRACT: Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. 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.

SUBMITTER: Roselli C 

PROVIDER: S-EPMC6136836 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Multi-ethnic genome-wide association study for atrial fibrillation.

Roselli Carolina C   Chaffin Mark D MD   Weng Lu-Chen LC   Aeschbacher Stefanie S   Ahlberg Gustav G   Albert Christine M CM   Almgren Peter P   Alonso Alvaro A   Anderson Christopher D CD   Aragam Krishna G KG   Arking Dan E DE   Barnard John J   Bartz Traci M TM   Benjamin Emelia J EJ   Bihlmeyer Nathan A NA   Bis Joshua C JC   Bloom Heather L HL   Boerwinkle Eric E   Bottinger Erwin B EB   Brody Jennifer A JA   Calkins Hugh H   Campbell Archie A   Cappola Thomas P TP   Carlquist John J   Chasman Daniel I DI   Chen Lin Y LY   Chen Yii-Der Ida YI   Choi Eue-Keun EK   Choi Seung Hoan SH   Christophersen Ingrid E IE   Chung Mina K MK   Cole John W JW   Conen David D   Cook James J   Crijns Harry J HJ   Cutler Michael J MJ   Damrauer Scott M SM   Daniels Brian R BR   Darbar Dawood D   Delgado Graciela G   Denny Joshua C JC   Dichgans Martin M   Dörr Marcus M   Dudink Elton A EA   Dudley Samuel C SC   Esa Nada N   Esko Tonu T   Eskola Markku M   Fatkin Diane D   Felix Stephan B SB   Ford Ian I   Franco Oscar H OH   Geelhoed Bastiaan B   Grewal Raji P RP   Gudnason Vilmundur V   Guo Xiuqing X   Gupta Namrata N   Gustafsson Stefan S   Gutmann Rebecca R   Hamsten Anders A   Harris Tamara B TB   Hayward Caroline C   Heckbert Susan R SR   Hernesniemi Jussi J   Hocking Lynne J LJ   Hofman Albert A   Horimoto Andrea R V R ARVR   Huang Jie J   Huang Paul L PL   Huffman Jennifer J   Ingelsson Erik E   Ipek Esra Gucuk EG   Ito Kaoru K   Jimenez-Conde Jordi J   Johnson Renee R   Jukema J Wouter JW   Kääb Stefan S   Kähönen Mika M   Kamatani Yoichiro Y   Kane John P JP   Kastrati Adnan A   Kathiresan Sekar S   Katschnig-Winter Petra P   Kavousi Maryam M   Kessler Thorsten T   Kietselaer Bas L BL   Kirchhof Paulus P   Kleber Marcus E ME   Knight Stacey S   Krieger Jose E JE   Kubo Michiaki M   Launer Lenore J LJ   Laurikka Jari J   Lehtimäki Terho T   Leineweber Kirsten K   Lemaitre Rozenn N RN   Li Man M   Lim Hong Euy HE   Lin Henry J HJ   Lin Honghuang H   Lind Lars L   Lindgren Cecilia M CM   Lokki Marja-Liisa ML   London Barry B   Loos Ruth J F RJF   Low Siew-Kee SK   Lu Yingchang Y   Lyytikäinen Leo-Pekka LP   Macfarlane Peter W PW   Magnusson Patrik K PK   Mahajan Anubha A   Malik Rainer R   Mansur Alfredo J AJ   Marcus Gregory M GM   Margolin Lauren L   Margulies Kenneth B KB   März Winfried W   McManus David D DD   Melander Olle O   Mohanty Sanghamitra S   Montgomery Jay A JA   Morley Michael P MP   Morris Andrew P AP   Müller-Nurasyid Martina M   Natale Andrea A   Nazarian Saman S   Neumann Benjamin B   Newton-Cheh Christopher C   Niemeijer Maartje N MN   Nikus Kjell K   Nilsson Peter P   Noordam Raymond R   Oellers Heidi H   Olesen Morten S MS   Orho-Melander Marju M   Padmanabhan Sandosh S   Pak Hui-Nam HN   Paré Guillaume G   Pedersen Nancy L NL   Pera Joanna J   Pereira Alexandre A   Porteous David D   Psaty Bruce M BM   Pulit Sara L SL   Pullinger Clive R CR   Rader Daniel J DJ   Refsgaard Lena L   Ribasés Marta M   Ridker Paul M PM   Rienstra Michiel M   Risch Lorenz L   Roden Dan M DM   Rosand Jonathan J   Rosenberg Michael A MA   Rost Natalia N   Rotter Jerome I JI   Saba Samir S   Sandhu Roopinder K RK   Schnabel Renate B RB   Schramm Katharina K   Schunkert Heribert H   Schurman Claudia C   Scott Stuart A SA   Seppälä Ilkka I   Shaffer Christian C   Shah Svati S   Shalaby Alaa A AA   Shim Jaemin J   Shoemaker M Benjamin MB   Siland Joylene E JE   Sinisalo Juha J   Sinner Moritz F MF   Slowik Agnieszka A   Smith Albert V AV   Smith Blair H BH   Smith J Gustav JG   Smith Jonathan D JD   Smith Nicholas L NL   Soliman Elsayed Z EZ   Sotoodehnia Nona N   Stricker Bruno H BH   Sun Albert A   Sun Han H   Svendsen Jesper H JH   Tanaka Toshihiro T   Tanriverdi Kahraman K   Taylor Kent D KD   Teder-Laving Maris M   Teumer Alexander A   Thériault Sébastien S   Trompet Stella S   Tucker Nathan R NR   Tveit Arnljot A   Uitterlinden Andre G AG   Van Der Harst Pim P   Van Gelder Isabelle C IC   Van Wagoner David R DR   Verweij Niek N   Vlachopoulou Efthymia E   Völker Uwe U   Wang Biqi B   Weeke Peter E PE   Weijs Bob B   Weiss Raul R   Weiss Stefan S   Wells Quinn S QS   Wiggins Kerri L KL   Wong Jorge A JA   Woo Daniel D   Worrall Bradford B BB   Yang Pil-Sung PS   Yao Jie J   Yoneda Zachary T ZT   Zeller Tanja T   Zeng Lingyao L   Lubitz Steven A SA   Lunetta Kathryn L KL   Ellinor Patrick T PT  

Nature genetics 20180611 9


Atrial fibrillation (AF) affects more than 33 million individuals worldwide<sup>1</sup> and has a complex heritability<sup>2</sup>. 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  ...[more]

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