Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.
Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,2...
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Public Library of Science (PLoS)
2011-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002158&type=printable |
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| author | Dan E Arking M Juhani Junttila Philippe Goyette Adriana Huertas-Vazquez Mark Eijgelsheim Marieke T Blom Christopher Newton-Cheh Kyndaron Reinier Carmen Teodorescu Audrey Uy-Evanado Naima Carter-Monroe Kari S Kaikkonen Marja-Leena Kortelainen Gabrielle Boucher Caroline Lagacé Anna Moes XiaoQing Zhao Frank Kolodgie Fernando Rivadeneira Albert Hofman Jacqueline C M Witteman André G Uitterlinden Roos F Marsman Raha Pazoki Abdennasser Bardai Rudolph W Koster Abbas Dehghan Shih-Jen Hwang Pallav Bhatnagar Wendy Post Gina Hilton Ronald J Prineas Man Li Anna Köttgen Georg Ehret Eric Boerwinkle Josef Coresh W H Linda Kao Bruce M Psaty Gordon F Tomaselli Nona Sotoodehnia David S Siscovick Greg L Burke Eduardo Marbán Peter M Spooner L Adrienne Cupples Jonathan Jui Karen Gunson Y Antero Kesäniemi Arthur A M Wilde Jean-Claude Tardif Christopher J O'Donnell Connie R Bezzina Renu Virmani Bruno H C H Stricker Hanno L Tan Christine M Albert Aravinda Chakravarti John D Rioux Heikki V Huikuri Sumeet S Chugh |
| author_facet | Dan E Arking M Juhani Junttila Philippe Goyette Adriana Huertas-Vazquez Mark Eijgelsheim Marieke T Blom Christopher Newton-Cheh Kyndaron Reinier Carmen Teodorescu Audrey Uy-Evanado Naima Carter-Monroe Kari S Kaikkonen Marja-Leena Kortelainen Gabrielle Boucher Caroline Lagacé Anna Moes XiaoQing Zhao Frank Kolodgie Fernando Rivadeneira Albert Hofman Jacqueline C M Witteman André G Uitterlinden Roos F Marsman Raha Pazoki Abdennasser Bardai Rudolph W Koster Abbas Dehghan Shih-Jen Hwang Pallav Bhatnagar Wendy Post Gina Hilton Ronald J Prineas Man Li Anna Köttgen Georg Ehret Eric Boerwinkle Josef Coresh W H Linda Kao Bruce M Psaty Gordon F Tomaselli Nona Sotoodehnia David S Siscovick Greg L Burke Eduardo Marbán Peter M Spooner L Adrienne Cupples Jonathan Jui Karen Gunson Y Antero Kesäniemi Arthur A M Wilde Jean-Claude Tardif Christopher J O'Donnell Connie R Bezzina Renu Virmani Bruno H C H Stricker Hanno L Tan Christine M Albert Aravinda Chakravarti John D Rioux Heikki V Huikuri Sumeet S Chugh |
| author_sort | Dan E Arking |
| collection | DOAJ |
| description | Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). |
| format | Article |
| id | doaj-art-66b3fe689b1d46a3b42f17472cd2611c |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2011-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-66b3fe689b1d46a3b42f17472cd2611c2025-08-20T02:30:55ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-06-0176e100215810.1371/journal.pgen.1002158Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.Dan E ArkingM Juhani JunttilaPhilippe GoyetteAdriana Huertas-VazquezMark EijgelsheimMarieke T BlomChristopher Newton-ChehKyndaron ReinierCarmen TeodorescuAudrey Uy-EvanadoNaima Carter-MonroeKari S KaikkonenMarja-Leena KortelainenGabrielle BoucherCaroline LagacéAnna MoesXiaoQing ZhaoFrank KolodgieFernando RivadeneiraAlbert HofmanJacqueline C M WittemanAndré G UitterlindenRoos F MarsmanRaha PazokiAbdennasser BardaiRudolph W KosterAbbas DehghanShih-Jen HwangPallav BhatnagarWendy PostGina HiltonRonald J PrineasMan LiAnna KöttgenGeorg EhretEric BoerwinkleJosef CoreshW H Linda KaoBruce M PsatyGordon F TomaselliNona SotoodehniaDavid S SiscovickGreg L BurkeEduardo MarbánPeter M SpoonerL Adrienne CupplesJonathan JuiKaren GunsonY Antero KesäniemiArthur A M WildeJean-Claude TardifChristopher J O'DonnellConnie R BezzinaRenu VirmaniBruno H C H StrickerHanno L TanChristine M AlbertAravinda ChakravartiJohn D RiouxHeikki V HuikuriSumeet S ChughSudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002158&type=printable |
| spellingShingle | Dan E Arking M Juhani Junttila Philippe Goyette Adriana Huertas-Vazquez Mark Eijgelsheim Marieke T Blom Christopher Newton-Cheh Kyndaron Reinier Carmen Teodorescu Audrey Uy-Evanado Naima Carter-Monroe Kari S Kaikkonen Marja-Leena Kortelainen Gabrielle Boucher Caroline Lagacé Anna Moes XiaoQing Zhao Frank Kolodgie Fernando Rivadeneira Albert Hofman Jacqueline C M Witteman André G Uitterlinden Roos F Marsman Raha Pazoki Abdennasser Bardai Rudolph W Koster Abbas Dehghan Shih-Jen Hwang Pallav Bhatnagar Wendy Post Gina Hilton Ronald J Prineas Man Li Anna Köttgen Georg Ehret Eric Boerwinkle Josef Coresh W H Linda Kao Bruce M Psaty Gordon F Tomaselli Nona Sotoodehnia David S Siscovick Greg L Burke Eduardo Marbán Peter M Spooner L Adrienne Cupples Jonathan Jui Karen Gunson Y Antero Kesäniemi Arthur A M Wilde Jean-Claude Tardif Christopher J O'Donnell Connie R Bezzina Renu Virmani Bruno H C H Stricker Hanno L Tan Christine M Albert Aravinda Chakravarti John D Rioux Heikki V Huikuri Sumeet S Chugh Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. PLoS Genetics |
| title | Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. |
| title_full | Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. |
| title_fullStr | Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. |
| title_full_unstemmed | Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. |
| title_short | Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. |
| title_sort | identification of a sudden cardiac death susceptibility locus at 2q24 2 through genome wide association in european ancestry individuals |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002158&type=printable |
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