Abstract
BACKGROUND: Obstructive sleep apnea (OSA), and other sleep disorders, are associated with increased risk of developing diabetes mellitus (DM). We examined whether sleep disorders influence the genetic risk of developing diabetes in Hispanic/Latino individuals. METHODS: We developed Type 2 Diabetes (T2D) polygenic risk score (T2D-PRS) useful in admixed Hispanic/Latino individuals. We estimated the association of the T2D-PRS with cross-sectional (n = 12,342) and incident (n = 6965) DM in the Hispanic Community Health Study/Study of Latinos (ages 18-76, 50.9% female). We conducted a mediation analysis with T2D-PRS as an exposure, incident DM as an outcome, and OSA as a mediator. Additionally, we performed Mendelian randomization (MR) analysis to assess the causal relationship between T2D and OSA. RESULTS: Here, we show that a 1 standard deviation increase in T2D-PRS has DM adjusted odds ratio (OR) = 2.67, 95% CI [2.40; 2.97] and a higher incident DM rate (incident rate ratio (IRR) = 2.02, 95% CI [1.75; 2.33]). In a stratified analysis based on OSA severity categories the associations are stronger in individuals with mild OSA compared to those with moderate to severe OSA. Mediation analysis suggests that OSA mediates the T2D-PRS association with DM. In two-sample MR analysis, T2D has a causal effect on OSA, OR = 1.03, 95% CI [1.01; 1.05], and OSA has a causal effect on T2D, with OR = 2.34, 95% CI [1.59; 3.44]. CONCLUSIONS: These results support a causal association between OSA and DM, with OSA mediating up to 4.7% of the genetic risk for DM. OSA treatment may reduce DM prevalence.