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

TitleMulti-ethnic genome-wide association study for atrial fibrillation.
Publication TypeJournal Article
Year of Publication2018
AuthorsRoselli C, Chaffin MD, Weng L-C, et al.
Secondary AuthorsEllinor PT
JournalNat Genet
Volume50
Issue9
Pagination1225-1233
Date Published2018 06 11
ISSN1546-1718
KeywordsAtrial Fibrillation, Case-Control Studies, Ethnic Groups, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Quantitative Trait Loci, Transcriptome
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.

DOI10.1038/s41588-018-0133-9
Alternate JournalNat Genet
PubMed ID29892015
PubMed Central IDPMC6136836
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
R01 HL139731 / HL / NHLBI NIH HHS / United States
16EIA26410001 / AHA / American Heart Association-American Stroke Association / 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