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. 2019 Sep 5:2:332.
doi: 10.1038/s42003-019-0579-z. eCollection 2019.

Sex-specific Mendelian randomization study of genetically predicted insulin and cardiovascular events in the UK Biobank

Jie V Zhao  1 , Shan Luo  1 , C Mary Schooling  1   2
Affiliations

Sex-specific Mendelian randomization study of genetically predicted insulin and cardiovascular events in the UK Biobank

Jie V Zhao et al. Commun Biol. .

Abstract

Insulin drives growth and reproduction which trade-off against longevity. Genetically predicted insulin, i.e., insulin proxied by genetic variants, is positively associated with ischemic heart disease, but sex differences are unclear, despite different disease rates and reproductive strategies by sex. We used Mendelian randomization in 392,010 white British from the UK Biobank to assess the sex-specific role of genetically predicted insulin in myocardial infarction (MI) (14,442 cases, 77% men), angina (21,939 cases, 65% men) and heart failure (5537 cases, 71% men). Genetically predicted insulin was associated with MI (odds ratio (OR) 4.27 per pmol/L higher insulin, 95% confidence interval (CI) 1.60 to 11.3) and angina (OR 2.93, 1.27 to 6.73) in men, but not women (MI OR 0.80, 95% CI 0.23 to 2.84, angina OR 1.10, 95% CI 0.38 to 3.18). Patterns were similar for insulin resistance and heart failure. Mitigating the effects of insulin might address sexual disparities in health.

Keywords: Genetic association study; Risk factors; Statistical methods.

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Conflict of interest statement

Competing interestsThe authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Associations of genetically predicted insulin and BMI-adjusted insulin with cardiovascular disease risk factors overall and by sex. ApoB apolipoprotein, BMI body mass index, DBP diastolic blood pressure, LDL low-density lipoprotein, SBP systolic blood pressure. Beta coefficients and 95% confidence intervals (CI) for the associations of insulin and BMI-adjusted insulin with CVD risk factors have been depicted. Gray denotes the 95% CI included the null, purple denotes the 95% CI did not include the null. n = 188,577 for LDL cholesterol, n = 24,925 for ApoB, n ≤ 361,194 for blood pressure and reticulocyte count
Fig. 2
Fig. 2
Flow chart of data sources
See this image and copyright information in PMC

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