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@article{Mitchell:2019:10.1161/JAHA.119.013751,
author = {Mitchell, RN and Ashar, FN and Jarvelin, M-R and Froguel, P and Sotoodehnia, N and Brody, JA and Sebert, S and Huikuri, H and Rioux, J and Goyette, P and Newcomb, CE and Junttila, MJ and Arking, DE},
doi = {10.1161/JAHA.119.013751},
journal = {Journal of the American Heart Association},
pages = {1--27},
title = {Effect of sex and underlying disease on the genetic association of QT interval and sudden cardiac death},
url = {http://dx.doi.org/10.1161/JAHA.119.013751},
volume = {8},
year = {2019}
}

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TY  - JOUR
AB  - BackgroundSudden cardiac death (SCD) accounts for ≈300 000 deaths annually in the United States. Men have a higher risk of SCD and are more likely to have underlying coronary artery disease, while women are more likely to have arrhythmic events in the setting of inherited or acquired QT prolongation. Moreover, there is evidence of sex differences in the genetics of QT interval duration. Using sex and coronary artery disease–stratified analyses, we assess differences in genetic association between longer QT interval and SCD risk.Methods and ResultsWe examined 2282 SCD subjects and 3561 Finnish controls. The SCD subjects were stratified by underlying disease (ischemic versus nonischemic) and by sex. We used logistic regression to test for association between the top QT interval–associated singlenucleotide polymorphism, rs12143842 (in the NOS1AP locus), and SCD risk. We also performed Mendelian randomization to test for causal association of QT interval in the various subgroups. No statistically significant differences were observed between the sexes for associations with rs12143842, despite the odds ratio being higher in females across all subgroup analyses. Consistent with our hypothesis, female nonischemics had the highest odds ratio point estimate for association between rs12143842 and SCD risk and male ischemics the lowest odds ratio point estimate (P=0.036 for difference). Similar trends were observed for the Mendelian randomization analysis.ConclusionsWhile individual subgroup comparisons did not achieve traditional criteria for statistical significance, this study is consistent with the hypothesis that the causal association of longer QT interval on SCD risk is stronger in women and nonischemic individuals.
AU  - Mitchell,RN
AU  - Ashar,FN
AU  - Jarvelin,M-R
AU  - Froguel,P
AU  - Sotoodehnia,N
AU  - Brody,JA
AU  - Sebert,S
AU  - Huikuri,H
AU  - Rioux,J
AU  - Goyette,P
AU  - Newcomb,CE
AU  - Junttila,MJ
AU  - Arking,DE
DO  - 10.1161/JAHA.119.013751
EP  - 27
PY  - 2019///
SN  - 2047-9980
SP  - 1
TI  - Effect of sex and underlying disease on the genetic association of QT interval and sudden cardiac death
T2  - Journal of the American Heart Association
UR  - http://dx.doi.org/10.1161/JAHA.119.013751
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000517997000032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.ahajournals.org/doi/10.1161/JAHA.119.013751
UR  - http://hdl.handle.net/10044/1/85495
VL  - 8
ER  -

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