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1. Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest

Author

Lemaitre, R.N. (Rozenn ), Johnson, C.O. (Catherine), Hesselson, S. (Stephanie), Sotoodhenia, N. (Nona), McKnight, B. (Barbara), Sitlani, C.M. (Colleen), Rea, D. (Dan), King, I.B. (Irena), Kwok, P.-Y. (Pui-Yan), Mak, A. (Angel), Li, G. (Guo), Brody, J.A. (Jennifer A.), Larson, E.B. (Eric), Mozaffarian, D. (Dariush), Psaty, B.M. (Bruce), Huertas-Vazquez, A. (Adriana), Tardif, J.-C. (Jean-Claude), Albert, C.M. (Christine), Lyytikäinen, L.-P. (Leo-Pekka), Arking, D.E. (Dan), Kääb, S. (Stefan), Huikuri, H.V. (Heikki), Krijthe, B.P. (Bouwe), Eijgelsheim, M. (Mark), Wang, Y.A. (Ying), Reinier, K. (Kyndaron), Lehtimäki, T. (Terho), Pulit, S.L. (Sara), Brugada, R. (Ramon), Müller-Nurasyid, M. (Martina), Newton-Cheh, C. (Christopher), Karhunen, P.J. (Pekka), Stricker, B.H.Ch. (Bruno), Goyette, P. (Philippe), Rotter, J.I. (Jerome), Chugh, S.S. (Sumeet), Chakravarti, A. (Aravinda), Jouven, X. (Xavier), Siscovick, D.S. (David), Lemaitre, R.N. (Rozenn ), Johnson, C.O. (Catherine), Hesselson, S. (Stephanie), Sotoodhenia, N. (Nona), McKnight, B. (Barbara), Sitlani, C.M. (Colleen), Rea, D. (Dan), King, I.B. (Irena), Kwok, P.-Y. (Pui-Yan), Mak, A. (Angel), Li, G. (Guo), Brody, J.A. (Jennifer A.), Larson, E.B. (Eric), Mozaffarian, D. (Dariush), Psaty, B.M. (Bruce), Huertas-Vazquez, A. (Adriana), Tardif, J.-C. (Jean-Claude), Albert, C.M. (Christine), Lyytikäinen, L.-P. (Leo-Pekka), Arking, D.E. (Dan), Kääb, S. (Stefan), Huikuri, H.V. (Heikki), Krijthe, B.P. (Bouwe), Eijgelsheim, M. (Mark), Wang, Y.A. (Ying), Reinier, K. (Kyndaron), Lehtimäki, T. (Terho), Pulit, S.L. (Sara), Brugada, R. (Ramon), Müller-Nurasyid, M. (Martina), Newton-Cheh, C. (Christopher), Karhunen, P.J. (Pekka), Stricker, B.H.Ch. (Bruno), Goyette, P. (Philippe), Rotter, J.I. (Jerome), Chugh, S.S. (Sumeet), Chakravarti, A. (Aravinda), Jouven, X. (Xavier), and Siscovick, D.S. (David)

Abstract

Background There is limited information on genetic factors associated with sudden cardiac arrest (SCA). Objective To assess the association of common variation in genes in fatty acid pathways with SCA risk. Methods We selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases. Results Eight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lo

Published
2014
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2. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals

Author

Arking, D.E. (Dan), Junttila, M.J. (Juhani), Goyette, P. (Philippe), Huertas-Vazquez, A. (Adriana), Eijgelsheim, M. (Mark), Blom, M.T. (Marieke), Newton-Cheh, C. (Christopher), Reinier, K. (Kyndaron), Teodorescu, C. (Carmen), Uy-Evanado, A. (Audrey), Carter-Monroe, N. (Naima), Kaikkonen, K.S. (Kari), Kortelainen, M.-L., Boucher, G. (Gabrielle), Lagacé, C. (Caroline), Moes, A. (Anna), Zhao, X., Kolodgie, F. (Frank), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Uitterlinden, A.G. (André), Marsman, R.F. (Roos), Pazoki, R. (Raha), Bardai, A. (Abdennasser), Koster, R.W. (Rudolph), Dehghan, A. (Abbas), Hwang, S.J., Bhatnagar, P. (Pallav), Post, W. (Wendy), Hilton, G. (Gina), Prineas, R.J. (Ronald), Li, M. (Man), Köttgen, A. (Anna), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Coresh, J. (Josef), Kao, W.H.L. (Wen), Psaty, B.M. (Bruce), Tomaselli, G.F. (Gordon), Sotoodehnia, N. (Nona), Siscovick, D.S. (David), Burke, G.L. (Greg), Marbán, E. (Eduardo), Spooner, P.M. (Peter), Cupples, L.A. (Adrienne), Jui, J. (Jonathan), Gunson, K. (Karen), Kesaniemi, Y.A. (Antero), Wilde, A.A.M. (Arthur), Tardif, J.-C. (Jean-Claude), O'Donnell, C.J. (Christopher), Bezzina, C.R. (Connie), Virmani, R. (Renu), Stricker, B.H.Ch. (Bruno), Tan, H.L. (Hanno), Albert, C.M. (Christine), Chakravarti, A. (Aravinda), Rioux, J.D. (John), Huikuri, H.V. (Heikki), Chugh, S.S. (Sumeet), Arking, D.E. (Dan), Junttila, M.J. (Juhani), Goyette, P. (Philippe), Huertas-Vazquez, A. (Adriana), Eijgelsheim, M. (Mark), Blom, M.T. (Marieke), Newton-Cheh, C. (Christopher), Reinier, K. (Kyndaron), Teodorescu, C. (Carmen), Uy-Evanado, A. (Audrey), Carter-Monroe, N. (Naima), Kaikkonen, K.S. (Kari), Kortelainen, M.-L., Boucher, G. (Gabrielle), Lagacé, C. (Caroline), Moes, A. (Anna), Zhao, X., Kolodgie, F. (Frank), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Witteman, J.C.M. (Jacqueline), Uitterlinden, A.G. (André), Marsman, R.F. (Roos), Pazoki, R. (Raha), Bardai, A. (Abdennasser), Koster, R.W. (Rudolph), Dehghan, A. (Abbas), Hwang, S.J., Bhatnagar, P. (Pallav), Post, W. (Wendy), Hilton, G. (Gina), Prineas, R.J. (Ronald), Li, M. (Man), Köttgen, A. (Anna), Ehret, G.B. (Georg), Boerwinkle, E.A. (Eric), Coresh, J. (Josef), Kao, W.H.L. (Wen), Psaty, B.M. (Bruce), Tomaselli, G.F. (Gordon), Sotoodehnia, N. (Nona), Siscovick, D.S. (David), Burke, G.L. (Greg), Marbán, E. (Eduardo), Spooner, P.M. (Peter), Cupples, L.A. (Adrienne), Jui, J. (Jonathan), Gunson, K. (Karen), Kesaniemi, Y.A. (Antero), Wilde, A.A.M. (Arthur), Tardif, J.-C. (Jean-Claude), O'Donnell, C.J. (Christopher), Bezzina, C.R. (Connie), Virmani, R. (Renu), Stricker, B.H.Ch. (Bruno), Tan, H.L. (Hanno), Albert, C.M. (Christine), Chakravarti, A. (Aravinda), Rioux, J.D. (John), Huikuri, H.V. (Heikki), and Chugh, S.S. (Sumeet)

Abstract

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

Published
2011
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