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

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


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.

MeSH terms

  • Alleles
  • Biological Specimen Banks
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / metabolism*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Insulin Resistance
  • Insulins / metabolism*
  • Male
  • Mendelian Randomization Analysis
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Factors
  • United Kingdom / epidemiology


  • Insulins