| Title: | Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis |
| Journal: | Diabetes Care |
| Published: | 4 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33277303/ |
| DOI: | https://doi.org/10.2337/dc20-1137 |
| URL: | https://care.diabetesjournals.org/content/diacare/44/2/556.full.pdf |
| Citations: | 25 (15 in last 2 years) as of 8 Aug 2024 |
Publication 5723
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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.</p>
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.</p>
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.</p>
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.</p>
15 Authors
- 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
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