Genetic risk score-based gene-smoking interaction association with heart failure Open Access

Wei, Qiying (Spring 2020)

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Background: Multiple genetic and environmental factors contribute to the individual’s risk for developing heart failure. Previous studies have focused on either genetic susceptibility or environmental risk factors (such as cigarette smoking) for heart failure. However, the gene-environmental interaction effect has not been well studied for heart failure. The goal of this study is to examine gene-smoking interactions on heart failure risk using a genetic risk score (GRS) based on recent findings from genome-wide association study (GWAS) of heart failure.

Methods: A heart failure GRS including 12 loci were calculated in the UK Biobank study to examine gene-smoking interactions with heart failure using logistic regression models, controlling for covariates including age, sex, alcohol intake frequency, body mass index, diabetes history and socioeconomic status. Additionally, the gene-smoking interaction of individual genetic variants association with heart failure was assessed.

Results: We identified significant synergistic interaction between the GRS and smoking status for heart failure. While GRS was positively associated with heart failure within ever-smokers or never-smokers, GRS was more strongly associated with heart failure among smokers (OR= 1.74 among ever-smokers, OR = 1.39 among never-smoker). Furthermore, compared to the low GRS group, smoking showed higher risk for heart failure among the high GRS group (OR = 1.28, 95%CI: 1.15-1.42), while the smoking effect was diminished among people with low GRS for heart failure (OR = 1.02, 95%CI: 0.90-1.16). In the analysis of a single genetic variant, we identified significant gene-smoking interaction of BAG3 locus on heart failure.

Conclusions: Genetic risk modifies the impact of smoking on heart failure. Cigarette smoking poses particularly higher risk among people with high genetic risk for heart failure.

Key words: Gene-environment interaction, genetics, smoking, heart failure, genetic risk score

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