Person:

Redline, Susan

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×(10^{−6}). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.

Background: Obstructive sleep apnea (OSA) is a common condition affecting more men than women. The relationship of OSA with microvascular disease is unclear, complicated by possible sex difference. Assessment of the relationship of OSA with retinal microvascular signs in men and women may provide insights into such a relationship. Methods and Results: We examined the sex‐specific cross‐sectional association of OSA severity with retinal vascular calibers in 1808 participants, and with specific retinopathy signs in 1831 participants from a sample of 2060 participants aged 54 to 93 years who underwent successful polysomnography in the Multi‐Ethnic Study of Atherosclerosis, 2010–2012. OSA severity was defined by the apnea–hypopnea index (events/h) as none (<5), mild (5–14.9), moderate (15–29.9), and severe (≥30). As compared to no OSA, moderate/severe OSA in men was associated with retinal arteriolar narrowing (odds ratio [OR] and 95% CI for the narrowest quartile: 1.65 [1.00–2.71]) and retinal venular widening (1.80 [1.07–3.04] for the widest quartile), but not in women (odds ratio: 1.10 [0.67–1.81] and 0.91 [0.58–1.43], respectively) after adjusting for age, race/ethnicity, body mass index, pack‐years of cigarette smoking, alcohol intake, hypertension duration, diabetes mellitus duration, HbA1c levels, lipid profile, micro‐/macroalbuminuria, estimated glomerular filtration rate, β‐blockers use, antihypertensive therapy, and lipid‐lowering therapy. In contrast, severe OSA was associated with retinal microaneurysms in women, but not in men (odds ratio: 3.22 [1.16–8.97] and 0.59 [0.27–1.30], respectively). Conclusions: The associations of OSA severity with retinal microvascular signs may differ by sex. Whether these findings were related to sex differences in OSA exposure needs further investigation.