{"doi":"10.2337/dc20-1137","title":"Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis","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.","journal":"Diabetes Care","year":2020,"id":97440,"datarank":1.2951903341904938,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.7662362554980695,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.7662362554980695,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":27,"citers_with_citation_signal":23,"citers_with_endowment":23,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.13135781"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":106144,"name":"Michael V. Holmes","orcid":"0000-0001-6617-0879","position":1,"is_corresponding":false},{"id":37303,"name":"J. Brent Richards","orcid":"0000-0002-3746-9086","position":2,"is_corresponding":false},{"id":108536,"name":"Tom Palmer","orcid":"0000-0003-4655-4511","position":3,"is_corresponding":false},{"id":267237,"name":"Vincenzo Forgetta","orcid":"0000-0002-6061-4720","position":4,"is_corresponding":false},{"id":21993,"name":"Cecilia M. Lindgren","orcid":"0000-0002-4903-9374","position":5,"is_corresponding":false},{"id":21948,"name":"Folkert W. Asselbergs","orcid":"0000-0002-1692-8669","position":6,"is_corresponding":false},{"id":27385,"name":"Christopher P. Nelson","orcid":"0000-0001-8025-2897","position":7,"is_corresponding":false},{"id":1113,"name":"Nilesh J. Samani","orcid":"0000-0002-3286-8133","position":8,"is_corresponding":false},{"id":1089,"name":"Mark I. McCarthy","orcid":"0000-0002-4393-0510","position":9,"is_corresponding":false},{"id":21799,"name":"Anubha Mahajan","orcid":"0000-0001-5585-3420","position":10,"is_corresponding":false},{"id":1528,"name":"George Davey Smith","orcid":"0000-0002-1407-8314","position":11,"is_corresponding":false},{"id":925,"name":"Mark Woodward","orcid":"0000-0001-9800-5296","position":12,"is_corresponding":false},{"id":481682,"name":"Linda M. O’Keeffe","orcid":"0000-0002-0003-0774","position":13,"is_corresponding":false},{"id":481683,"name":"Sanne A. E. Peters","orcid":"0000-0003-0346-5412","position":14,"is_corresponding":false},{"id":481681,"name":"Tricia M. Peters","orcid":"0000-0002-5037-0427","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T22:35:34.520494Z","pmid":"33277303","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}