title: Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.
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.
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington. Electronic address: rozenl@uw.edu.
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Catherine O
authors.initials: CO
authors.lastname: Johnson
authors.affiliation: Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, California.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hesselson
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodhenia
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Sitlani
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Rea
authors.affiliation: Department of Medicine, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, California.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, California.
authors.forename: Angel
authors.initials: A
authors.lastname: Mak
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brody
authors.affiliation: Group Health Research Institute, Seattle, Washington.
authors.forename: Eric
authors.initials: E
authors.lastname: Larson
authors.affiliation: Department of Epidemiology, Harvard University, Boston, Massachusetts; Divisions of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington; Health Services, University of Washington, Seattle, Washington; Group Health Research Institute, Seattle, Washington.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Cedars-Sinai Medical Center, Heart Institute, Los Angeles, California.
authors.forename: Adriana
authors.initials: A
authors.lastname: Huertas-Vazquez
authors.affiliation: Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Divisions of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Albert
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.affiliation: Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University and Munich Heart Alliance, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.affiliation: Institute of Clinical Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland.
authors.forename: Heikki V
authors.initials: HV
authors.lastname: Huikuri
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging [NCHA], The Netherlands.
authors.forename: Bouwe P
authors.initials: BP
authors.lastname: Krijthe
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Eijgelsheim
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.affiliation: Cedars-Sinai Medical Center, Heart Institute, Los Angeles, California.
authors.forename: Kyndaron
authors.initials: K
authors.lastname: Reinier
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Program in Medical and Population Genetics, the Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pulit
authors.affiliation: Cardiovascular Genetics Center, Institut Investigació Biomèdica de Girona IDIBGI-Universitat de Girona, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.affiliation: Department of Medicine I, University Hospital Grosshadern, and Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Nurasyid
authors.affiliation: Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Framingham Heart Study, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Massachusetts.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Newton-Cheh
authors.affiliation: Department of Forensic Medicine, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging [NCHA], The Netherlands; Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Goyette
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute, Torrance, California; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Cedars-Sinai Medical Center, Heart Institute, Los Angeles, California.
authors.forename: Sumeet S
authors.initials: SS
authors.lastname: Chugh
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Department of Cardiology, University Paris Descartes, Paris, France; Department of Epidemiology, University Paris Descartes, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics*; D000368:Aged; D000465:Algorithms; D000483:Alleles; D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac; D005227:Fatty Acids / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D005227:Fatty Acids; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human
keywords: Death; Genetic epidemiology; Sudden