TY - JOUR
T1 - Sudden cardiac arrest and rare genetic variants in the community
AU - Milano, Annalisa
AU - Blom, Marieke T.
AU - Lodder, Elisabeth M.
AU - Van Hoeijen, Daniel A.
AU - Barc, Julien
AU - Koopmann, Tamara T.
AU - Bardai, Abdennasser
AU - Beekman, Leander
AU - Lichtner, Peter
AU - Van Den Berg, Maarten P.
AU - Wilde, Arthur A.M.
AU - Bezzina, Connie R.
AU - Tan, Hanno L.
N1 - Publisher Copyright: © 2016 American Heart Association, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Background - Sudden cardiac arrest (SCA) ranks among the most common causes of death worldwide. Because SCA is most often lethal, yet mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCA could save many lives. In unselected SCA victims from the community, common genetic variants (which are not disease-causing per se, but may increase susceptibility to ventricular fibrillation) are found to be associated with increased SCA risk. However, whether rare genetic variants contribute to SCA risk in the community is largely unexplored. Methods and Results - We here investigated the involvement of rare genetic variants in SCA risk at the population level by studying the prevalence of 6 founder genetic variants present in the Dutch population (PLN-p.Arg14del, MYBPC3-p.Trp792fsX17, MYBPC3-p.Arg943X, MYBPC3-p.Pro955fsX95, PKP2-p.Arg79X, and the Chr7q36 idiopathic ventricular fibrillation risk haplotype) in a cohort of 1440 unselected Dutch SCA victims included in the Amsterdam Resuscitation Study (ARREST). The six studied founder mutations were found to be more prevalent (1.1%) in the ARREST SCA cohort compared with an ethnically and geographically matched set of controls (0.4%, n=1379; P<0.05) or a set of Dutch individuals drawn from the Genome of the Netherlands (GoNL) study (0%, n=500; P<0.02). Conclusions - This finding provides proof-of-concept for the notion that rare genetic variants contribute to some extent to SCA risk in the community.
AB - Background - Sudden cardiac arrest (SCA) ranks among the most common causes of death worldwide. Because SCA is most often lethal, yet mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCA could save many lives. In unselected SCA victims from the community, common genetic variants (which are not disease-causing per se, but may increase susceptibility to ventricular fibrillation) are found to be associated with increased SCA risk. However, whether rare genetic variants contribute to SCA risk in the community is largely unexplored. Methods and Results - We here investigated the involvement of rare genetic variants in SCA risk at the population level by studying the prevalence of 6 founder genetic variants present in the Dutch population (PLN-p.Arg14del, MYBPC3-p.Trp792fsX17, MYBPC3-p.Arg943X, MYBPC3-p.Pro955fsX95, PKP2-p.Arg79X, and the Chr7q36 idiopathic ventricular fibrillation risk haplotype) in a cohort of 1440 unselected Dutch SCA victims included in the Amsterdam Resuscitation Study (ARREST). The six studied founder mutations were found to be more prevalent (1.1%) in the ARREST SCA cohort compared with an ethnically and geographically matched set of controls (0.4%, n=1379; P<0.05) or a set of Dutch individuals drawn from the Genome of the Netherlands (GoNL) study (0%, n=500; P<0.02). Conclusions - This finding provides proof-of-concept for the notion that rare genetic variants contribute to some extent to SCA risk in the community.
KW - arrhythmia
KW - cardiac arrest
KW - founder mutations
KW - genetics
KW - population genetics
UR - http://www.scopus.com/inward/record.url?scp=84966293793&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCGENETICS.115.001263
DO - https://doi.org/10.1161/CIRCGENETICS.115.001263
M3 - Article
C2 - 26800703
SN - 1942-325X
VL - 9
SP - 147
EP - 153
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 2
ER -