Hernesniemi, J.A.* ; Lyytikäinen, L.-P.* ; Oksala, N.* ; Seppälä, I.* ; Kleber, M.E.* ; Mononen, N.* ; Marz, W.* ; Mikkelsson, J.* ; Pessi, T.* ; Louhelainen, A.M.* ; Martiskainen, M.* ; Nikus, K.* ; Klopp, N. ; Waldenberger, M. ; Illig, T. ; Kähönen, M.* ; Laaksonen, R.* ; Karhunen, P.J.* ; Lehtimäki, T.*
Predicting sudden cardiac death using common genetic risk variants for coronary artery disease.
Eur. Heart J. 36, 1669-1675 (2015)
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 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)]. CONCLUSION: Genetic risk estimate for CAD may also be used to predict SCD.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Coronary Artery Disease ; Death ; Genetics ; Sudden; Genome-wide Association; Mendelian Randomization; Heart-disease; Qt Interval; Reclassification; Polymorphism; Population; Pathways
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2015
Prepublished im Jahr
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0195-668X
e-ISSN
1522-9645
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 36,
Heft: 26,
Seiten: 1669-1675
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Oxford University Press
Verlagsort
Oxford
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504091-001
Förderungen
Copyright
Erfassungsdatum
2015-04-26