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

Lemaitre, RN and Johnson, CO and Hesselson, S and Sotoodhenia, N and McKnight, B and Sitlani, CM and Rea, TD and King, IB and Kwok, PY and Mak, A and Li, G and Brody, J and Larson, E and Mozaffarian, D and Psaty, BM and Huertas-Vazquez, A and Tardif, JC and Albert, CM and Lyytikainen, LP and Arking, DE and Kaab, S and Huikuri, HV and Krijthe, BP and Eijgelsheim, M and Wang, YA and Reinier, K and Lehtimaki, T and Pulit, SL and Brugada, R and Muller-Nurasyid, M and Newton-Cheh, CH and Karhunen, PJ and Stricker, BH and Goyette, P and Rotter, JI and Chugh, SS and Chakravarti, A and Jouven, X and Siscovick, DS (2014) Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. Heart Rhythm. pp. 471-477.

Abstract

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

Item Type: Article
Additional Information: NIBR author: institute: NIBR contributor address: [Lemaitre, Rozenn N.; Johnson, Catherine O.; Sotoodhenia, Nona; Sitlani, Colleen M.; Rea, Thomas D.; Li, Guo; Brody, Jennifer; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Hesselson, Stephanie; Kwok, Pui-Yan; Mak, Angel] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Hesselson, Stephanie; Kwok, Pui-Yan; Mak, Angel] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [King, Irena B.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Larson, Eric; Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA. [Mozaffarian, Dariush] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. [Mozaffarian, Dariush; Albert, Christine M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Pulit, Sara L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Huertas-Vazquez, Adriana; Reinier, Kyndaron; Chugh, Sumeet S.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Tardif, Jean-Claude; Goyette, Philippe] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Tardif, Jean-Claude; Goyette, Philippe] Univ Montreal, Montreal, PQ, Canada. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Karhunen, Pekka J.] Fimlab Labs, Dept Forens Med, Tampere, Finland. [Karhunen, Pekka J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kaeaeb, Stefan; Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Huikuri, Heikki V.] Univ Oulu, Med Res Ctr Oulu, Inst Clin Med, Oulu, Finland. [Krijthe, Bouwe P.; Eijgelsheim, Mark; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Wang, Ying A.] Novartis Inst BioMed Res, Cambridge, MA USA. [Pulit, Sara L.] Broad Inst Massachusetts Inst Technol & Harvard U, Program Med & Populat Genet, Cambridge, MA USA. [Brugada, Ramon] IDIBGI Univ Girona, Inst Invest Biomed Girona, Cardiovasc Genet Ctr, Girona, Spain. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Newton-Cheh, Chris H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Chris H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Chris H.] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. [Stricker, Bruno H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands. [Rotter, Jerome I.] Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Jouven, Xavier] Univ Paris 05, Dept Cardiol, Paris, France. [Jouven, Xavier] Univ Paris 05, Dept Epidemiol, Paris, France.
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/23414

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