Multi-ethnic genome-wide association study for atrial fibrillation

Carolina Roselli; Mark D. Chaffin; Lu-Chen Weng; Stefanie Aeschbacher; Gustav Ahlberg; Christine M. Albert; Peter Almgren; Alvaro Alonso; Christopher D. Anderson; Krishna G. Aragam; Dan E. Arking; John Barnard; Traci M. Bartz; Emelia J. Benjamin; Nathan A. Bihlmeyer; Joshua C. Bis; Heather L. Bloom; Eric Boerwinkle; Erwin B. Bottinger; Jennifer A. Brody; Hugh Calkins; Archie Campbell; Thomas P. Cappola; John Carlquist; Daniel I. Chasman; Lin Y. Chen; Yii-Der Ida Chen; Eue-Keun Choi; Seung Hoan Choi; Ingrid E. Christophersen; Mina K. Chung; John W. Cole; David Conen; James Cook; Harry J. Crijns; Michael J. Cutler; Scott M. Damrauer; Brian R. Daniels; Dawood Darbar; Graciela Delgado; Joshua C. Denny; Martin Dichgans; Marcus Doerr; Elton A. Dudink; Lars Lind; Ruth J. F. Loos; Morten S. Olesen; Lena Refsgaard; Jesper H. Svendsen; Peter Ejvin Weeke; et al.; Steven A Lubitz; Kathryn L Lunetta; Patrick T Ellinor

doi:10.1038/s41588-018-0133-9

Multi-ethnic genome-wide association study for atrial fibrillation

Carolina Roselli, Mark D. Chaffin, Lu-Chen Weng, Stefanie Aeschbacher, Gustav Ahlberg, Christine M. Albert, Peter Almgren, Alvaro Alonso, Christopher D. Anderson, Krishna G. Aragam, Dan E. Arking, John Barnard, Traci M. Bartz, Emelia J. Benjamin, Nathan A. Bihlmeyer, Joshua C. Bis, Heather L. Bloom, Eric Boerwinkle, Erwin B. Bottinger, Jennifer A. BrodyHugh Calkins, Archie Campbell, Thomas P. Cappola, John Carlquist, Daniel I. Chasman, Lin Y. Chen, Yii-Der Ida Chen, Eue-Keun Choi, Seung Hoan Choi, Ingrid E. Christophersen, Mina K. Chung, John W. Cole, David Conen, James Cook, Harry J. Crijns, Michael J. Cutler, Scott M. Damrauer, Brian R. Daniels, Dawood Darbar, Graciela Delgado, Joshua C. Denny, Martin Dichgans, Marcus Doerr, Elton A. Dudink, Lars Lind, Ruth J. F. Loos, Morten S. Olesen, Lena Refsgaard, Jesper H. Svendsen, Peter Ejvin Weeke, et al., Steven A Lubitz, Kathryn L Lunetta, Patrick T Ellinor

Research output: Contribution to journal › Journal article › Research › peer-review

487 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Genetics
Volume	50
Issue number	9
Pages (from-to)	1225-1233
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0133-9
Publication status	Published - Sep 2018

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Roselli, C., Chaffin, M. D., Weng, L-C., Aeschbacher, S., Ahlberg, G., Albert, C. M., Almgren, P., Alonso, A., Anderson, C. D., Aragam, K. G., Arking, D. E., Barnard, J., Bartz, T. M., Benjamin, E. J., Bihlmeyer, N. A., Bis, J. C., Bloom, H. L., Boerwinkle, E., Bottinger, E. B., ... Ellinor, P. T. (2018). Multi-ethnic genome-wide association study for atrial fibrillation. Nature Genetics, 50(9), 1225-1233. https://doi.org/10.1038/s41588-018-0133-9

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; Alonso, Alvaro; Anderson, Christopher D.; Aragam, Krishna G.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Benjamin, Emelia J.; Bihlmeyer, Nathan A.; Bis, Joshua C.; Bloom, Heather L.; Boerwinkle, Eric; Bottinger, Erwin B.; Brody, Jennifer A.; Calkins, Hugh; Campbell, Archie; Cappola, Thomas P.; Carlquist, John; Chasman, Daniel I.; Chen, Lin Y.; Chen, Yii-Der Ida; Choi, Eue-Keun; Choi, Seung Hoan; Christophersen, Ingrid E.; Chung, Mina K.; Cole, John W.; Conen, David; Cook, James; Crijns, Harry J.; Cutler, Michael J.; Damrauer, Scott M.; Daniels, Brian R.; Darbar, Dawood; Delgado, Graciela; Denny, Joshua C.; Dichgans, Martin; Doerr, Marcus; Dudink, Elton A.; Lind, Lars; Loos, Ruth J. F.; Olesen, Morten S.; Refsgaard, Lena; Svendsen, Jesper H.; Weeke, Peter Ejvin; et al.; Lubitz, Steven A; Lunetta, Kathryn L; Ellinor, Patrick T.

In: Nature Genetics, Vol. 50, No. 9, 09.2018, p. 1225-1233.

Research output: Contribution to journal › Journal article › Research › peer-review

Roselli, C, Chaffin, MD, Weng, L-C, Aeschbacher, S, Ahlberg, G, Albert, CM, Almgren, P, Alonso, A, Anderson, CD, Aragam, KG, Arking, DE, Barnard, J, Bartz, TM, Benjamin, EJ, Bihlmeyer, NA, Bis, JC, Bloom, HL, Boerwinkle, E, Bottinger, EB, Brody, JA, Calkins, H, Campbell, A, Cappola, TP, Carlquist, J, Chasman, DI, Chen, LY, Chen, Y-DI, Choi, E-K, Choi, SH, Christophersen, IE, Chung, MK, Cole, JW, Conen, D, Cook, J, Crijns, HJ, Cutler, MJ, Damrauer, SM, Daniels, BR, Darbar, D, Delgado, G, Denny, JC, Dichgans, M, Doerr, M, Dudink, EA, Lind, L, Loos, RJF , Olesen, MS, Refsgaard, L, Svendsen, JH, Weeke, PE, et al., Lubitz, SA, Lunetta, KL & Ellinor, PT 2018, 'Multi-ethnic genome-wide association study for atrial fibrillation', Nature Genetics, vol. 50, no. 9, pp. 1225-1233. https://doi.org/10.1038/s41588-018-0133-9

Roselli, Carolina ; Chaffin, Mark D. ; Weng, Lu-Chen ; Aeschbacher, Stefanie ; Ahlberg, Gustav ; Albert, Christine M. ; Almgren, Peter ; Alonso, Alvaro ; Anderson, Christopher D. ; Aragam, Krishna G. ; Arking, Dan E. ; Barnard, John ; Bartz, Traci M. ; Benjamin, Emelia J. ; Bihlmeyer, Nathan A. ; Bis, Joshua C. ; Bloom, Heather L. ; Boerwinkle, Eric ; Bottinger, Erwin B. ; Brody, Jennifer A. ; Calkins, Hugh ; Campbell, Archie ; Cappola, Thomas P. ; Carlquist, John ; Chasman, Daniel I. ; Chen, Lin Y. ; Chen, Yii-Der Ida ; Choi, Eue-Keun ; Choi, Seung Hoan ; Christophersen, Ingrid E. ; Chung, Mina K. ; Cole, John W. ; Conen, David ; Cook, James ; Crijns, Harry J. ; Cutler, Michael J. ; Damrauer, Scott M. ; Daniels, Brian R. ; Darbar, Dawood ; Delgado, Graciela ; Denny, Joshua C. ; Dichgans, Martin ; Doerr, Marcus ; Dudink, Elton A. ; Lind, Lars ; Loos, Ruth J. F. ; Olesen, Morten S. ; Refsgaard, Lena ; Svendsen, Jesper H. ; Weeke, Peter Ejvin ; et al. ; Lubitz, Steven A ; Lunetta, Kathryn L ; Ellinor, Patrick T. / Multi-ethnic genome-wide association study for atrial fibrillation. In: Nature Genetics. 2018 ; Vol. 50, No. 9. pp. 1225-1233.

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title = "Multi-ethnic genome-wide association study for atrial fibrillation",

abstract = "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.",

author = "Carolina Roselli and Chaffin, {Mark D.} and Lu-Chen Weng and Stefanie Aeschbacher and Gustav Ahlberg and Albert, {Christine M.} and Peter Almgren and Alvaro Alonso and Anderson, {Christopher D.} and Aragam, {Krishna G.} and Arking, {Dan E.} and John Barnard and Bartz, {Traci M.} and Benjamin, {Emelia J.} and Bihlmeyer, {Nathan A.} and Bis, {Joshua C.} and Bloom, {Heather L.} and Eric Boerwinkle and Bottinger, {Erwin B.} and Brody, {Jennifer A.} and Hugh Calkins and Archie Campbell and Cappola, {Thomas P.} and John Carlquist and Chasman, {Daniel I.} and Chen, {Lin Y.} and Chen, {Yii-Der Ida} and Eue-Keun Choi and Choi, {Seung Hoan} and Christophersen, {Ingrid E.} and Chung, {Mina K.} and Cole, {John W.} and David Conen and James Cook and Crijns, {Harry J.} and Cutler, {Michael J.} and Damrauer, {Scott M.} and Daniels, {Brian R.} and Dawood Darbar and Graciela Delgado and Denny, {Joshua C.} and Martin Dichgans and Marcus Doerr and Dudink, {Elton A.} and Lars Lind and Loos, {Ruth J. F.} and Olesen, {Morten S.} and Lena Refsgaard and Svendsen, {Jesper H.} and Weeke, {Peter Ejvin} and {et al.} and Lubitz, {Steven A} and Lunetta, {Kathryn L} and Ellinor, {Patrick T}",

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AU - Roselli, Carolina

AU - Chaffin, Mark D.

AU - Weng, Lu-Chen

AU - Aeschbacher, Stefanie

AU - Ahlberg, Gustav

AU - Albert, Christine M.

AU - Almgren, Peter

AU - Alonso, Alvaro

AU - Anderson, Christopher D.

AU - Aragam, Krishna G.

AU - Arking, Dan E.

AU - Barnard, John

AU - Bartz, Traci M.

AU - Benjamin, Emelia J.

AU - Bihlmeyer, Nathan A.

AU - Bis, Joshua C.

AU - Bloom, Heather L.

AU - Boerwinkle, Eric

AU - Bottinger, Erwin B.

AU - Brody, Jennifer A.

AU - Calkins, Hugh

AU - Campbell, Archie

AU - Cappola, Thomas P.

AU - Carlquist, John

AU - Chasman, Daniel I.

AU - Chen, Lin Y.

AU - Chen, Yii-Der Ida

AU - Choi, Eue-Keun

AU - Choi, Seung Hoan

AU - Christophersen, Ingrid E.

AU - Chung, Mina K.

AU - Cole, John W.

AU - Conen, David

AU - Cook, James

AU - Crijns, Harry J.

AU - Cutler, Michael J.

AU - Damrauer, Scott M.

AU - Daniels, Brian R.

AU - Darbar, Dawood

AU - Delgado, Graciela

AU - Denny, Joshua C.

AU - Dichgans, Martin

AU - Doerr, Marcus

AU - Dudink, Elton A.

AU - Lind, Lars

AU - Loos, Ruth J. F.

AU - Olesen, Morten S.

AU - Refsgaard, Lena

AU - Svendsen, Jesper H.

AU - Weeke, Peter Ejvin

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AB - 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.

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DO - 10.1038/s41588-018-0133-9

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VL - 50

SP - 1225

EP - 1233

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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