TY - JOUR
T1 - Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest
AU - Lemaitre, Rozenn N.
AU - Johnson, Catherine O.
AU - Hesselson, Stephanie
AU - Sotoodhenia, Nona
AU - McKnight, Barbara
AU - Sitlani, Colleen M.
AU - Rea, Thomas D.
AU - King, Irena B.
AU - Kwok, Pui Yan
AU - Mak, Angel
AU - Li, Guo
AU - Brody, Jennifer
AU - Larson, Eric
AU - Mozaffarian, Dariush
AU - Psaty, Bruce M.
AU - Huertas-Vazquez, Adriana
AU - Tardif, Jean Claude
AU - Albert, Christine M.
AU - Lyytikäinen, Leo Pekka
AU - Arking, Dan E.
AU - Kääb, Stefan
AU - Huikuri, Heikki V.
AU - Krijthe, Bouwe P.
AU - Eijgelsheim, Mark
AU - Wang, Ying A.
AU - Reinier, Kyndaron
AU - Lehtimäki, Terho
AU - Pulit, Sara L.
AU - Brugada, Ramon
AU - Müller-Nurasyid, Martina
AU - Newton-Cheh, Chris H.
AU - Karhunen, Pekka J.
AU - Stricker, Bruno H.
AU - Goyette, Philippe
AU - Rotter, Jerome I.
AU - Chugh, Sumeet S.
AU - Chakravarti, Aravinda
AU - Jouven, Xavier
AU - Siscovick, David S.
N1 - Funding Information:
The Sudden Cardiac Blood Repository Study was financed by the National Lung, Heart, and Blood Institute (grants RO1-HL092144 , RO1-HL092111 , and RO1-HL088456 ). Funding sources for the other contributing studies are listed in the Online Supplement.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Death
KW - Genetic epidemiology
KW - Sudden
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U2 - 10.1016/j.hrthm.2014.01.008
DO - 10.1016/j.hrthm.2014.01.008
M3 - Article
C2 - 24418166
AN - SCOPUS:84894585484
SN - 1547-5271
VL - 11
SP - 471
EP - 477
JO - Heart Rhythm
JF - Heart Rhythm
IS - 3
ER -