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

Nat Genet
Authors
Carolina Roselli
Mark Chaffin
Lu-Chen Weng
Stefanie Aeschbacher
Gustav Ahlberg
Christine Albert
Peter Almgren
Alvaro Alonso
Christopher Anderson
Krishna Aragam
Dan Arking
John Barnard
Traci Bartz
Emelia Benjamin
Nathan Bihlmeyer
Joshua Bis
Heather Bloom
Eric Boerwinkle
Erwin Bottinger
Jennifer Brody
Hugh Calkins
Archie Campbell
Thomas Cappola
John Carlquist
Daniel Chasman
Lin Chen
Yii-Der Chen
Eue-Keun Choi
Seung Choi
Ingrid Christophersen
Mina Chung
John Cole
David Conen
James Cook
Harry Crijns
Michael Cutler
Scott Damrauer
Brian Daniels
Dawood Darbar
Graciela Delgado
Joshua Denny
Martin Dichgans
Marcus Dorr
Elton Dudink
Samuel Dudley
Nada Esa
Tõnu Esko
Markku Eskola
Diane Fatkin
Stephan Felix
Ian Ford
Oscar Franco
Bastiaan Geelhoed
Raji Grewal
Vilmundur Gudnason
Xiuqing Guo
Namrata Gupta
Stefan Gustafsson
Rebecca Gutmann
Anders Hamsten
Tamara Harris
Caroline Hayward
Susan Heckbert
Jussi Hernesniemi
Lynne Hocking
Albert Hofman
Andrea Horimoto
Jie Huang
Paul Huang
Jennifer Huffman
Erik Ingelsson
Esra Ipek
Kaoru Ito
Jordi Jimenez-Conde
Renee Johnson
J Wouter Jukema
Stefan Kääb
Mika Kähönen
Yoichiro Kamatani
John Kane
Adnan Kastrati
Sekar Kathiresan
Petra Katschnig-Winter
Maryam Kavousi
Thorsten Kessler
Bas Kietselaer
Paulus Kirchhof
Marcus Kleber
Stacey Knight
Jose Krieger
Michiaki Kubo
Lenore Launer
Jari Laurikka
Terho Lehtimäki
Kirsten Leineweber
Rozenn Lemaitre
Man Li
Hong Lim
Henry Lin
Honghuang Lin
Lars Lind
Cecilia Lindgren
Marja-Liisa Lokki
Barry London
Ruth Loos
Siew-Kee Low
Yingchang Lu
Leo-Pekka Lyytikäinen
Peter Macfarlane
Patrik Magnusson
Anubha Mahajan
Rainer Malik
Alfredo Mansur
Gregory Marcus
Lauren Margolin
Kenneth Margulies
Winfried März
David McManus
Olle Melander
Sanghamitra Mohanty
Jay Montgomery
Michael Morley
Andrew Morris
Martina Müller-Nurasyid
Andrea Natale
Saman Nazarian
Benjamin Neumann
Christopher Newton-Cheh
Maartje Niemeijer
Kjell Nikus
Peter Nilsson
Raymond Noordam
Heidi Oellers
Morten Olesen
Marju Orho-Melander
Sandosh Padmanabhan
Hui-Nam Pak
Guillaume Pare
Nancy Pedersen
Joanna Pera
Alexandre Pereira
David Porteous
Bruce Psaty
Sara Pulit
Clive Pullinger
Daniel Rader
Lena Refsgaard
Marta Ribasés
Paul Ridker
Michiel Rienstra
Lorenz Risch
Dan Roden
Jonathan Rosand
Michael Rosenberg
Natalia Rost
Jerome Rotter
Samir Saba
Roopinder Sandhu
Renate Schnabel
Katharina Schramm
Heribert Schunkert
Claudia Schurman
Stuart Scott
Ilkka Seppälä
Christian Shaffer
Svati Shah
Alaa Shalaby
Jaemin Shim
M Benjamin Shoemaker
Joylene Siland
Juha Sinisalo
Moritz Sinner
Agnieszka Slowik
Albert Smith
Blair Smith
J Gustav Smith
Jonathan Smith
Nicholas Smith
Elsayed Soliman
Nona Sotoodehnia
Bruno Stricker
Albert Sun
Han Sun
Jesper Svendsen
Toshihiro Tanaka
Kahraman Tanriverdi
Kent Taylor
Maris Teder-Laving
Alexander Teumer
Sébastien Thériault
Stella Trompet
Nathan Tucker
Arnljot Tveit
André Uitterlinden
Pim van der Harst
Isabelle Van Gelder
David Van Wagoner
Niek Verweij
Efthymia Vlachopoulou
Uwe Volker
Biqi Wang
Peter Weeke
Bob Weijs
Raul Weiss
Stefan Weiss
Quinn Wells
Kerri Wiggins
Jorge Wong
Daniel Woo
Bradford Worrall
Pil-Sung Yang
Jie Yao
Zachary Yoneda
Tanja Zeller
Lingyao Zeng
Steven Lubitz
Kathryn Lunetta
Patrick Ellinor
Keywords
Humans
Genetic Predisposition to Disease
Transcriptome
Genome-Wide Association Study
Quantitative Trait Loci
Case-Control Studies
Atrial Fibrillation
Ethnicity
Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. 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.
Year of Publication
2018
Journal
Nat Genet
Volume
50
Issue
9
Pages
1225-1233
Date Published
2018 06 11
ISSN
1546-1718
DOI
10.1038/s41588-018-0133-9
PubMed ID
29892015
PubMed Central ID
PMC6136836
Links
Grant list
U01 HG007417 / HG / NHGRI NIH HHS / United States
R01 HL139731 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL138737 / HL / NHLBI NIH HHS / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
R01 HL111314 / HL / NHLBI NIH HHS / United States
K23 HL127296 / HL / NHLBI NIH HHS / United States
MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
2014105 / DDCF / Doris Duke Charitable Foundation / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
R01 HL092217 / HL / NHLBI NIH HHS / United States
L30 HL123413 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
T32 GM007569 / GM / NIGMS NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
U01 HL130114 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
16EIA26410001 / AHA / American Heart Association-American Stroke Association / United States
R01 HL090620 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States

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