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Multi-ethnic genome-wide association study for atrial fibrillation
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.ORCID iD: 0000-0002-1234-5562
Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
Univ Hosp Basel, Basel, Switzerland;Cardiovasc Res Inst Basel, Basel, Switzerland.
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2018 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 9, p. 1225-1233Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 50, no 9, p. 1225-1233
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Medical Genetics
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URN: urn:nbn:se:uu:diva-364160DOI: 10.1038/s41588-018-0133-9ISI: 000443151300012PubMedID: 29892015OAI: oai:DiVA.org:uu-364160DiVA, id: diva2:1259998
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-10-31Bibliographically approved

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Chaffin, Mark D.Alonso, AlvaroBihlmeyer, Nathan A.Gustafsson, StefanIngelsson, ErikKahonen, MikaKirchhof, PaulusLind, LarsPulit, Sara L.Risch, LorenzVerweij, Niek
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