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 |
DOIs | |
Publication status | Published - 01-06-2017 |
All Science Journal Classification (ASJC) codes
- Genetics
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Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. / Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A.; Low, Siew Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurmann, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R.V.R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati H.; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge A.; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann-Heimbach, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J.F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; Van Der Harst, Pim; Lokki, Marja Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.
In: Nature Genetics, Vol. 49, No. 6, 01.06.2017, p. 946-952.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation
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 - Hopewell, Jemma C.
AU - Debette, Stephanie
AU - Chauhan, Ganesh
AU - Yang, Qiong
AU - Worrall, Bradford B.
AU - Paré, Guillaume
AU - Kamatani, Yoichiro
AU - Hagemeijer, Yanick P.
AU - Verweij, Niek
AU - Siland, Joylene E.
AU - Kubo, Michiaki
AU - Smith, Jonathan D.
AU - Van Wagoner, David R.
AU - Bis, Joshua C.
AU - Perz, Siegfried
AU - Psaty, Bruce M.
AU - Ridker, Paul M.
AU - Magnani, Jared W.
AU - Harris, Tamara B.
AU - Launer, Lenore J.
AU - Shoemaker, M. Benjamin
AU - Padmanabhan, Sandosh
AU - Haessler, Jeffrey
AU - Bartz, Traci M.
AU - Waldenberger, Melanie
AU - Lichtner, Peter
AU - Arendt, Marina
AU - Krieger, Jose E.
AU - Kähönen, Mika
AU - Risch, Lorenz
AU - Mansur, Alfredo J.
AU - Peters, Annette
AU - Smith, Blair H.
AU - Lind, Lars
AU - Scott, Stuart A.
AU - Lu, Yingchang
AU - Bottinger, Erwin B.
AU - Hernesniemi, Jussi
AU - Lindgren, Cecilia M.
AU - Wong, Jorge A.
AU - Huang, Jie
AU - Eskola, Markku
AU - Morris, Andrew P.
AU - Ford, Ian
AU - Reiner, Alex P.
AU - Delgado, Graciela
AU - Chen, Lin Y.
AU - Chen, Yii Der Ida
AU - Sandhu, Roopinder K.
AU - Li, Man
AU - Boerwinkle, Eric
AU - Eisele, Lewin
AU - Lannfelt, Lars
AU - Rost, Natalia
AU - Anderson, Christopher D.
AU - Taylor, Kent D.
AU - Campbell, Archie
AU - Magnusson, Patrik K.
AU - Porteous, David
AU - Hocking, Lynne J.
AU - Vlachopoulou, Efthymia
AU - Pedersen, Nancy L.
AU - Nikus, Kjell
AU - Orho-Melander, Marju
AU - Hamsten, Anders
AU - Heeringa, Jan
AU - Denny, Joshua C.
AU - Kriebel, Jennifer
AU - Darbar, Dawood
AU - Newton-Cheh, Christopher
AU - Shaffer, Christian
AU - Macfarlane, Peter W.
AU - Heilmann-Heimbach, Stefanie
AU - Almgren, Peter
AU - Huang, Paul L.
AU - Sotoodehnia, Nona
AU - Soliman, Elsayed Z.
AU - Uitterlinden, Andre G.
AU - Hofman, Albert
AU - Franco, Oscar H.
AU - Völker, Uwe
AU - Jöckel, Karl Heinz
AU - Sinner, Moritz F.
AU - Lin, Henry J.
AU - Guo, Xiuqing
AU - Dichgans, Martin
AU - Ingelsson, Erik
AU - Kooperberg, Charles
AU - Melander, Olle
AU - Loos, Ruth J.F.
AU - Laurikka, Jari
AU - Conen, David
AU - Rosand, Jonathan
AU - Van Der Harst, Pim
AU - Lokki, Marja Liisa
AU - Kathiresan, Sekar
AU - Pereira, Alexandre
AU - Jukema, J. Wouter
AU - Hayward, Caroline
AU - Rotter, Jerome I.
AU - März, Winfried
AU - Lehtimäki, Terho
AU - Stricker, Bruno H.
AU - Chung, Mina K.
AU - Felix, Stephan B.
AU - Gudnason, Vilmundur
AU - Alonso, Alvaro
AU - Roden, Dan M.
AU - Kääb, Stefan
AU - Chasman, Daniel I.
AU - Heckbert, Susan R.
AU - Benjamin, Emelia J.
AU - Tanaka, Toshihiro
AU - Lunetta, Kathryn L.
AU - Lubitz, Steven A.
AU - Ellinor, Patrick T.
N1 - Publisher Copyright: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/6/1
Y1 - 2017/6/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85017510399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017510399&partnerID=8YFLogxK
U2 - 10.1038/ng.3843
DO - 10.1038/ng.3843
M3 - Article
C2 - 28416818
AN - SCOPUS:85017510399
VL - 49
SP - 946
EP - 952
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 6
ER -