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.
Plain Language Summary
Sleep disorders such as obstructive sleep apnea play a role in diabetes. Here, we used genetic data to assess this role in over 12,000 Hispanic/Latino individuals. We developed a polygenic risk score summarizing genetic liability to diabetes, and showed that individuals with higher values of this genetic risk score are more likely to develop diabetes. We found that some of the genetic risk of diabetes is mediated via obstructive sleep apnea. Additionally, we implemented a genetic data analysis method called Mendelian randomization, finding that obstructive sleep apnea causally increases risk of diabetes. These results suggest that further studies should consider treating obstructive sleep apnea to potentially reduce diabetes prevalence.
Hrytsenko et al. analyze the role of obstructive sleep apnea (OSA) in diabetes mellitus (DM) risk using polygenic risk scores and mendelian randomization in a Hispanic and Latino community. Results reveal that OSA mediates the genetic risk for DM and there is a bidirectional causal relationship between OSA and DM.