Predicting sudden cardiac death using common genetic risk variants for coronary artery disease

• Verfasst von: Hernesniemi, Jussi A. [VerfasserIn]
• Verfasst von: Kleber, Marcus E. [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Titel: Predicting sudden cardiac death using common genetic risk variants for coronary artery disease
• Verf.angabe: Jussi A. Hernesniemi, Leo-Pekka Lyytikäinen, Niku Oksala, Ilkka Seppälä, Marcus E. Kleber, Nina Mononen, Winfried März, Jussi Mikkelsson, Tanja Pessi, Anne-Mari Louhelainen, Mika Martiskainen, Kjell Nikus, Norman Klopp, Melanie Waldenberger, Thomas Illig, Mika Kähönen, Reijo Laaksonen, Pekka J. Karhunen, and Terho Lehtimäki
• E-Jahr: 2015
• Jahr: 23 April 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 22.01.2018
• Titel Quelle: Enthalten in: European heart journal
• Ort Quelle: Oxford : Oxford University Press, 1980
• Jahr Quelle: 2015
• Band/Heft Quelle: 36(2015), 26, Seite 1669-1675
• ISSN Quelle: 1522-9645
• DOI: doi:10.1093/eurheartj/ehv106
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1567482589

Abstract

Aims: 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).Methods and 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 r2 < 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]. Conclusion: Genetic risk estimate for CAD may also be used to predict SCD.