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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest

Ashar, FN; Mitchell, RN; Albert, CM; Newton-Cheh, C; Brody, JA; Mueller-Nurasyid, M; Moes, A; ... Sotoodehnia, N; + view all (2018) A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. European Heart Journal , 39 (44) pp. 3961-3969. 10.1093/eurheartj/ehy474. Green open access

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Abstract

Aims 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. Methods and results 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. Conclusions 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 factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

Type: Article
Title: A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/eurheartj/ehy474
Publisher version: https://doi.org/10.1093/eurheartj/ehy474
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, Sudden cardiac arrest, Genome-wide association study, Mendelian randomization, MENDELIAN RANDOMIZATION, RISK-FACTOR, ATHEROSCLEROSIS-RISK, DEATH, VARIANTS, POPULATION, FIBRILLATION, INTERVAL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/10070234
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