Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

Diabetes Care. 2021 Feb;44(2):556-562. doi: 10.2337/dc20-1137. Epub 2020 Dec 4.

Abstract

Objective: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding.

Research design and methods: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment.

Results: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08-1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17-1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs.

Conclusions: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Disease* / etiology
  • Coronary Disease* / genetics
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide
  • Sex Factors*

Associated data

  • figshare/10.2337/figshare.13135781