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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest

Ashar, Foram N; Franks, Paul LU ; Engström, Thomas LU ; Arking, Dan E; Sotoodehnia, Nona and , (2018) In European Heart Journal 39(44). p.3961-3969
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Heart Journal
volume
39
issue
44
pages
9 pages
publisher
Oxford University Press
external identifiers
  • scopus:85056802981
ISSN
1522-9645
DOI
10.1093/eurheartj/ehy474
language
English
LU publication?
yes
id
2f647862-915a-43a0-942f-14653d6811ab
date added to LUP
2018-11-27 08:27:49
date last changed
2019-04-23 04:42:57
@article{2f647862-915a-43a0-942f-14653d6811ab,
  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.},
  author       = {Ashar, Foram N and Franks, Paul and Engström, Thomas and Arking, Dan E and Sotoodehnia, Nona and , },
  issn         = {1522-9645},
  language     = {eng},
  number       = {44},
  pages        = {3961--3969},
  publisher    = {Oxford University Press},
  series       = {European Heart Journal},
  title        = {A comprehensive evaluation of the genetic architecture of sudden cardiac arrest},
  url          = {http://dx.doi.org/10.1093/eurheartj/ehy474},
  volume       = {39},
  year         = {2018},
}