
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.09.10.24313336
preprint
1
Article
Obstructive sleep apnea mediates genetic risk of Diabetes Mellitus: The Hispanic Community Health Study/Study of Latinos
Hrytsenko Yana http://orcid.org/0000-0002-4683-8883

Spitzer Brian W.
Wang Heming http://orcid.org/0000-0002-1486-7495

Bertisch Suzanne M.
Taylor Kent
Garcia-Bedoya Olga
Ramos Alberto R
Daviglus Martha L.
Gallo Linda C
Isasi Carmen
Cai Jianwen
Qi Qibin
Alcantara Carmela
Redline Susan
Sofer Tamar http://orcid.org/0000-0001-8520-8860

10 9 2024
2024.09.10.24313336https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.09.10.24313336
nihpp-2024.09.10.24313336.pdf
Abstract

Objective

We sought to evaluate whether obstructive sleep apnea (OSA), and other sleep disorders, increase genetic risk of developing diabetes mellitus (DM).

Research Design and Methods

Using GWAS summary statistics from the DIAGRAM consortium and Million Veteran Program, we developed multi-ancestry Type 2 Diabetes (T2D) polygenic risk scores (T2D-PRSs) useful in admixed Hispanic/Latino individuals. We estimated the association of the T2D-PRS with cross-sectional and incident DM in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We conducted a mediation analysis with T2D-PRSs 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

Of 12,342 HCHS/SOL participants, at baseline, 48.4% were normoglycemic, 36.6% were hyperglycemic, and 15% had diabetes, and 50.9% identified as female. Mean age was 41.5, and mean BMI was 29.4. T2D-PRSs was strongly associated with baseline DM and with incident DM. At baseline, a 1 SD increase in the primary T2D-PRS had 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 were stronger in individuals with mild OSA compared to those with moderate to severe OSA. Mediation analysis suggested that OSA mediates the T2D-PRS association with DM. In two-sample MR analysis, T2D-PRS had a causal effect on OSA, OR = 1.03, 95% CI [1.01; 1.05], and OSA had a causal effect on T2D, with OR = 2.34, 95% CI [1.59; 3.44].

Conclusions

OSA likely mediates genetic effects on T2D.
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