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Multi-ethnic genome-wide association study for atrial fibrillation

Roselli, Carolina; Chaffin, Mark D.; Weng, Lu Chen; Aeschbacher, Stefanie; Ahlberg, Gustav; Albert, Christine M.; Almgren, Peter LU ; Alonso, Alvaro; Anderson, Christopher D. and Aragam, Krishna G., et al. (2018) In Nature Genetics 50(9). p.1225-1233
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... (More)

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.

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Nature Genetics
volume
50
issue
9
pages
1225 - 1233
publisher
Nature Publishing Group
external identifiers
  • scopus:85048317620
ISSN
1061-4036
DOI
10.1038/s41588-018-0133-9
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English
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yes
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30ecd6a3-425a-4417-816b-1da549b2bd4c
date added to LUP
2018-06-25 16:34:30
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2019-02-03 05:33:34
@article{30ecd6a3-425a-4417-816b-1da549b2bd4c,
  abstract     = {<p>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 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.</p>},
  author       = {Roselli, Carolina and Chaffin, Mark D. and Weng, Lu Chen and Aeschbacher, Stefanie and Ahlberg, Gustav and Albert, Christine M. and Almgren, Peter and Alonso, Alvaro and Anderson, Christopher D. and Aragam, Krishna G. and Arking, Dan E. and Barnard, John and Bartz, Traci M. and Benjamin, Emelia J. and Bihlmeyer, Nathan A. and Bis, Joshua C. and Bloom, Heather L. and Boerwinkle, Eric and Bottinger, Erwin B. and Brody, Jennifer A. and Calkins, Hugh and Campbell, Archie and Cappola, Thomas P. and Carlquist, John and Chasman, Daniel I. and Chen, Lin Y. and Chen, Yii Der Ida and Choi, Eue Keun and Choi, Seung Hoan and Christophersen, Ingrid E. and Chung, Mina K. and Cole, John W. and Conen, David and Cook, James and Crijns, Harry J. and Cutler, Michael J. and Damrauer, Scott M. and Daniels, Brian R. and Darbar, Dawood and Delgado, Graciela and Denny, Joshua C. and Dichgans, Martin and Dörr, Marcus and Dudink, Elton A. and Dudley, Samuel C. and Gustafsson, Stefan and Lindgren, Cecilia M. and Melander, Olle and Nilsson, Peter and Orho-Melander, Marju and Lubitz, Steven A and Lunetta, Kathryn L and Ellinor, Patrick T},
  issn         = {1061-4036},
  language     = {eng},
  number       = {9},
  pages        = {1225--1233},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Multi-ethnic genome-wide association study for atrial fibrillation},
  url          = {http://dx.doi.org/10.1038/s41588-018-0133-9},
  volume       = {50},
  year         = {2018},
}