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

Tricia M. Peters | Zendy; Michael V. Holmes | Zendy; J. Brent Richards | Zendy; Tom Palmer | Zendy; Vincenzo Forgetta | Zendy; Cecilia M. Lindgren | Zendy; Folkert W. Asselbergs | Zendy; Christopher P. Nelson | Zendy; Nilesh J. Samani | Zendy; Mark I. McCarthy | Zendy; Anubha Mahajan | Zendy; George Davey Smith | Zendy; Mark Woodward | Zendy; Linda M. O’Keeffe | Zendy; Sanne A. E. Peters | Zendy

Open Access

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

Author(s) -

Tricia M. Peters,

Michael V. Holmes,

J. Brent Richards,

Tom Palmer,

Vincenzo Forgetta,

Cecilia M. Lindgren,

Folkert W. Asselbergs,

Christopher P. Nelson,

Nilesh J. Samani,

Mark I. McCarthy,

Anubha Mahajan,

George Davey Smith,

Mark Woodward,

Linda M. O’Keeffe,

Sanne A. E. Peters

Publication year - 2020

Publication title -

diabetes care

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.636

H-Index - 363

eISSN - 1935-5548

pISSN - 0149-5992

DOI - 10.2337/dc20-1137

Subject(s) - mendelian randomization , medicine , diabetes mellitus , type 2 diabetes , randomization , coronary heart disease , disease , cardiology , randomized controlled trial , endocrinology , genetics , gene , genotype , genetic variants , biology

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.

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