title: Predicting sudden cardiac death using common genetic risk variants for coronary artery disease.
abstract: OBJECTIVE
  Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD).
  
  
  RESULTS
  A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)].
  
  
  CONCLUSIONS
  Genetic risk estimate for CAD may also be used to predict SCD.
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland North Karelia Central Hospital, Tikkamäentie 16, Joensuu 80210, Finland jussi.hernesniemi@uta.fi.
authors.forename: Jussi A
authors.initials: JA
authors.lastname: Hernesniemi
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland Department of Vascular Surgery, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Department of Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Mononen
authors.affiliation: Department of Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany Synlab Academy, Synlab Services GmbH, Mannheim, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Department of Forensic Medicine, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland Satakunta Central Hospital, Pori, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Mikkelsson
authors.affiliation: Department of Forensic Medicine, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland The Pirkanmaa Hospital District's Science Centre, Tampere, Finland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pessi
authors.affiliation: Department of Forensic Medicine, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Anne-Mari
authors.initials: AM
authors.lastname: Louhelainen
authors.affiliation: Department of Forensic Medicine, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Martiskainen
authors.affiliation: Department of Cardiology, Heart Hospital and University of Tampere Medical School, Tampere, Finland.
authors.forename: Kjell
authors.initials: K
authors.lastname: Nikus
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany Hannover Unified Biobank, Hannover Medical School, Hannover, Germany Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Department of Clinical Physiology, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: Department of Forensic Medicine, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.affiliation: Department of Clinical Chemistry, University of Tampere, Tampere University Hospital and Fimlab Laboratories, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000368:Aged; D001344:Autopsy; D003324:Coronary Artery Disease / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: Coronary artery disease; Death; Genetics; Sudden