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 Dörr; Elton A. Dudink; Samuel C. Dudley; Stefan Gustafsson; Cecilia M. Lindgren; Olle Melander; Peter Nilsson; Marju Orho-Melander; 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 Dörr, Elton A. Dudink, Samuel C. Dudley, Stefan Gustafsson, Cecilia M. Lindgren, Olle Melander, Peter Nilsson, Marju Orho-Melander, Steven A Lubitz, Kathryn L Lunetta, Patrick T Ellinor

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	1225-1233
Tidskrift	Nature Genetics
Volym	50
Nummer	9
Tidigt onlinedatum	2018 juni 11
DOI	https://doi.org/10.1038/s41588-018-0133-9
Status	Published - 2018 sep.

Ämnesklassifikation (UKÄ)

Medicinsk genetik

Tillgång till dokument

10.1038/s41588-018-0133-9

Andra filer och länkar

Link to publication in Scopus

Citera det här

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

@article{30ecd6a3425a4417816b1da549b2bd4c,

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

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 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 Weng, {Lu Chen} 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 Choi, {Eue Keun} 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 D{\"o}rr and Dudink, {Elton A.} and Dudley, {Samuel C.} and Stefan Gustafsson and Lindgren, {Cecilia M.} and Olle Melander and Peter Nilsson and Marju Orho-Melander and Lubitz, {Steven A} and Lunetta, {Kathryn L} and Ellinor, {Patrick T}",

year = "2018",

month = sep,

doi = "10.1038/s41588-018-0133-9",

language = "English",

volume = "50",

pages = "1225--1233",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

Roselli, C, Chaffin, MD, Weng, LC, 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, YDI, Choi, EK, 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, Dörr, M, Dudink, EA, Dudley, SC, Gustafsson, S, Lindgren, CM, Melander, O , Nilsson, P , Orho-Melander, M, Lubitz, SA, Lunetta, KL & Ellinor, PT 2018, 'Multi-ethnic genome-wide association study for atrial fibrillation', Nature Genetics, vol. 50, nr. 9, s. 1225-1233. https://doi.org/10.1038/s41588-018-0133-9

TY - JOUR

T1 - Multi-ethnic genome-wide association study for atrial fibrillation

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 - Dörr, Marcus

AU - Dudink, Elton A.

AU - Dudley, Samuel C.

AU - Gustafsson, Stefan

AU - Lindgren, Cecilia M.

AU - Melander, Olle

AU - Nilsson, Peter

AU - Orho-Melander, Marju

AU - Lubitz, Steven A

AU - Lunetta, Kathryn L

AU - Ellinor, Patrick T

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048317620&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0133-9

DO - 10.1038/s41588-018-0133-9

M3 - Article

C2 - 29892015

AN - SCOPUS:85048317620

SN - 1061-4036

VL - 50

SP - 1225

EP - 1233

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Multi-ethnic genome-wide association study for atrial fibrillation

Sammanfattning

Ämnesklassifikation (UKÄ)

Tillgång till dokument

Andra filer och länkar

Fingeravtryck

Citera det här