Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

AFGen Consortium; Ingrid E Christophersen; Michiel Rienstra; Carolina Roselli; Xiaoyan Yin; Bastiaan Geelhoed; John Barnard; Honghuang Lin; Dan E Arking; Albert V Smith; Christine M Albert; Mark Chaffin; Nathan R Tucker; Molong Li; Derek Klarin; Nathan A Bihlmeyer; Siew-Kee Low; Peter E Weeke; Martina Müller-nurasyid; J Gustav Smith; Jennifer A Brody; Maartje N Niemeijer; Marcus Dörr; Stella Trompet; Jennifer Huffman; Stefan Gustafsson; Claudia Schurmann; Marcus E Kleber; Leo-Pekka Lyytikäinen; Ilkka Seppälä; Rainer Malik; Andrea R V R Horimoto; Marco Perez; Juha Sinisalo; Stefanie Aeschbacher; Sébastien Thériault; Jie Yao; Farid Radmanesh; Stefan Weiss; Alexander Teumer; Seung Hoan Choi; Lu-Chen Weng; Sebastian Clauss; Rajat Deo; Daniel J Rader; Svati H Shah; Albert Sun; Andrew P Morris; Archie Campbell; David Porteous; METASTROKE Consortium of the ISGC; The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium; Caroline Hayward

doi:10.1038/ng.3843

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

AFGen Consortium, Ingrid E Christophersen, Michiel Rienstra, Carolina Roselli, Xiaoyan Yin, Bastiaan Geelhoed, John Barnard, Honghuang Lin, Dan E Arking, Albert V Smith, Christine M Albert, Mark Chaffin, Nathan R Tucker, Molong Li, Derek Klarin, Nathan A Bihlmeyer, Siew-Kee Low, Peter E Weeke, Martina Müller-nurasyid, J Gustav SmithJennifer A Brody, Maartje N Niemeijer, Marcus Dörr, Stella Trompet, Jennifer Huffman, Stefan Gustafsson, Claudia Schurmann, Marcus E Kleber, Leo-Pekka Lyytikäinen, Ilkka Seppälä, Rainer Malik, Andrea R V R Horimoto, Marco Perez, Juha Sinisalo, Stefanie Aeschbacher, Sébastien Thériault, Jie Yao, Farid Radmanesh, Stefan Weiss, Alexander Teumer, Seung Hoan Choi, Lu-Chen Weng, Sebastian Clauss, Rajat Deo, Daniel J Rader, Svati H Shah, Albert Sun, Andrew P Morris, Archie Campbell, David Porteous, METASTROKE Consortium of the ISGC, The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Caroline Hayward

Research output: Contribution to journal › Article › peer-review

Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

Original language	English
Pages (from-to)	946-952
Number of pages	7
Journal	Nature Genetics
Volume	49
Issue number	6
Early online date	17 Apr 2017
DOIs	https://doi.org/10.1038/ng.3843
Publication status	Published - Jun 2017

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Journal Article

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10.1038/ng.3843

Large‐scale analyses of common and rare variants identify 12 new lociAccepted author manuscript, 303 KB

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AFGen Consortium, Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., Lin, H., Arking, D. E., Smith, A. V., Albert, C. M., Chaffin, M., Tucker, N. R., Li, M., Klarin, D., Bihlmeyer, N. A., Low, S.-K., Weeke, P. E., Müller-nurasyid, M., ... Hayward, C. (2017). Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nature Genetics, 49(6), 946-952. https://doi.org/10.1038/ng.3843

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abstract = "Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.",

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author = "\{AFGen Consortium\} and Christophersen, \{Ingrid E\} and Michiel Rienstra and Carolina Roselli and Xiaoyan Yin and Bastiaan Geelhoed and John Barnard and Honghuang Lin and Arking, \{Dan E\} and Smith, \{Albert V\} and Albert, \{Christine M\} and Mark Chaffin and Tucker, \{Nathan R\} and Molong Li and Derek Klarin and Bihlmeyer, \{Nathan A\} and Siew-Kee Low and Weeke, \{Peter E\} and Martina M{\"u}ller-nurasyid and Smith, \{J Gustav\} and Brody, \{Jennifer A\} and Niemeijer, \{Maartje N\} and Marcus D{\"o}rr and Stella Trompet and Jennifer Huffman and Stefan Gustafsson and Claudia Schurmann and Kleber, \{Marcus E\} and Leo-Pekka Lyytik{\"a}inen and Ilkka Sepp{\"a}l{\"a} and Rainer Malik and Horimoto, \{Andrea R V R\} and Marco Perez and Juha Sinisalo and Stefanie Aeschbacher and S{\'e}bastien Th{\'e}riault and Jie Yao and Farid Radmanesh and Stefan Weiss and Alexander Teumer and Choi, \{Seung Hoan\} and Lu-Chen Weng and Sebastian Clauss and Rajat Deo and Rader, \{Daniel J\} and Shah, \{Svati H\} and Albert Sun and Morris, \{Andrew P\} and Archie Campbell and David Porteous and \{METASTROKE Consortium of the ISGC\} and \{The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium\} and Caroline Hayward",

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doi = "10.1038/ng.3843",

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journal = "Nature Genetics",

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AFGen Consortium, Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, AV, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Müller-nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Dörr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikäinen, L-P, Seppälä, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Thériault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Choi, SH, Weng, L-C, Clauss, S, Deo, R, Rader, DJ, Shah, SH, Sun, A, Morris, AP, Campbell, A, Porteous, D, METASTROKE Consortium of the ISGC, The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium & Hayward, C 2017, 'Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation', Nature Genetics, vol. 49, no. 6, pp. 946-952. https://doi.org/10.1038/ng.3843

TY - JOUR

T1 - Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

AU - AFGen Consortium

AU - Christophersen, Ingrid E

AU - Rienstra, Michiel

AU - Roselli, Carolina

AU - Yin, Xiaoyan

AU - Geelhoed, Bastiaan

AU - Barnard, John

AU - Lin, Honghuang

AU - Arking, Dan E

AU - Smith, Albert V

AU - Albert, Christine M

AU - Chaffin, Mark

AU - Tucker, Nathan R

AU - Li, Molong

AU - Klarin, Derek

AU - Bihlmeyer, Nathan A

AU - Low, Siew-Kee

AU - Weeke, Peter E

AU - Müller-nurasyid, Martina

AU - Smith, J Gustav

AU - Brody, Jennifer A

AU - Niemeijer, Maartje N

AU - Dörr, Marcus

AU - Trompet, Stella

AU - Huffman, Jennifer

AU - Gustafsson, Stefan

AU - Schurmann, Claudia

AU - Kleber, Marcus E

AU - Lyytikäinen, Leo-Pekka

AU - Seppälä, Ilkka

AU - Malik, Rainer

AU - Horimoto, Andrea R V R

AU - Perez, Marco

AU - Sinisalo, Juha

AU - Aeschbacher, Stefanie

AU - Thériault, Sébastien

AU - Yao, Jie

AU - Radmanesh, Farid

AU - Weiss, Stefan

AU - Teumer, Alexander

AU - Choi, Seung Hoan

AU - Weng, Lu-Chen

AU - Clauss, Sebastian

AU - Deo, Rajat

AU - Rader, Daniel J

AU - Shah, Svati H

AU - Sun, Albert

AU - Morris, Andrew P

AU - Campbell, Archie

AU - Porteous, David

AU - METASTROKE Consortium of the ISGC

AU - The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

AU - Hayward, Caroline

PY - 2017/6

Y1 - 2017/6

N2 - Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

AB - Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

KW - Journal Article

U2 - 10.1038/ng.3843

DO - 10.1038/ng.3843

M3 - Article

C2 - 28416818

SN - 1061-4036

VL - 49

SP - 946

EP - 952

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

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Stratifying Resilience and Depression Longitudinally

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Caroline Hayward

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Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

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Stratifying Resilience and Depression Longitudinally

Generation Scotland

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Caroline Hayward

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