Genetic subtypes of diabetes may differ in their association with cardiovascular outcomes. A study published in Diabetes Care evaluated whether polygenic risk scores (PRSs) for five adult-onset diabetes subtypes are associated with incident diabetes and coronary artery disease (CAD) in the general population.

The analysis used data from the Malmö Diet and Cancer cohort, which included 24,025 participants. Polygenic risk scores were calculated for five diabetes subtypes, including moderate obesity-related diabetes (MOD). Incident diabetes and CAD were assessed during follow-up. Genetic correlation and causal relationships between MOD and CAD were further evaluated using genome-wide association study data for MOD (N=4,116) and CAD (N=296,525).

During a median follow-up of 24.0 years for diabetes and 24.6 years for CAD, 4,105 participants (17.1%) developed diabetes and 3,841 (16.0%) developed CAD. The polygenic risk score for MOD (PRSMOD) was associated with incident diabetes and CAD. Participants in the highest tertile of PRSMOD had a 1.10-fold higher risk of developing CAD compared with those in the lowest tertile.

A positive genetic correlation between MOD and CAD was reported. Mendelian randomization analysis indicated a causal effect of MOD on CAD. Genetic susceptibility across all five subtypes was related to incident diabetes, while only MOD showed an association with incident CAD. These findings indicate that higher genetic risk for MOD may be relevant for identifying CAD risk in the general population.