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

RN Lemaitre, CO Johnson, S Hesselson, N Sotoodhenia, B McKnight, CM Sitlani, TD Rea, IB King, PY Kwok, A Mak, G Li, J Brody, E Larson, D Mozaffarian, BM Psaty, A Huertas-Vazquez, JC Tardif, CM Albert, LP Lyytikainen, DE ArkingS Kaab, HV Huikuri, Bouwe Krijthe, Mark Eijgelsheim, YA Wang, K Reinier, T Lehtimaki, SL Pulit, R Brugada, M Muller-Nurasyid, CH Newton-Cheh, PJ Karhunen, Bruno Stricker, P Goyette, JI Rotter, SS Chugh, A Chakravarti, X Jouven, DS Siscovick

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BACKGROUND There is limited information on genetic factors OBJECTIVE To assess the association of common variation in associated with sudden cardiac arrest (SCA). 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 SN Ps 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 CPCAT1 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 /a lower SCA risk ( 9 5 % confidence interval 16% to 1%) in the replication phase. CONCLUSIONS While none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation. (C) 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)471-477
Number of pages7
JournalHeart Rhythm
Issue number3
Publication statusPublished - 2014

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  • EMC NIHES-01-64-03

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