A comprehensive evaluation of the genetic architecture of sudden cardiac arrest.

European Heart Journal
Foram N AsharNona Sotoodehnia

Abstract

Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing f...Continue Reading

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Citations

Nov 22, 2019·Journal of the American Heart Association·Rebecca N MitchellDan E Arking
Jan 30, 2020·Circulation·Salim S ViraniUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
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Mar 7, 2019·European Heart Journal·Thomas F Lüscher
Nov 21, 2020·European Heart Journal·Thomas F Lüscher
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Aug 28, 2021·Experimental and Therapeutic Medicine·Nenghua ZhangGengqian Zhang

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