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

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

Research output: Contribution to journalArticle

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% lower SCA risk (95% 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.

Original languageEnglish (US)
Pages (from-to)471-477
Number of pages7
JournalHeart Rhythm
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2014

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Keywords

  • Death
  • Genetic epidemiology
  • Sudden

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lemaitre, R. N., Johnson, C. O., Hesselson, S., Sotoodhenia, N., McKnight, B., Sitlani, C. M., Rea, T. D., King, I. B., Kwok, P. Y., Mak, A., Li, G., Brody, J., Larson, E., Mozaffarian, D., Psaty, B. M., Huertas-Vazquez, A., Tardif, J. C., Albert, C. M., Lyytikäinen, L. P., ... Siscovick, D. S. (2014). Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. Heart Rhythm, 11(3), 471-477. https://doi.org/10.1016/j.hrthm.2014.01.008