Abstract
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.
Highlights
Obstructive sleep apnea (OSA) is a common disorder characterized by collapse of the upper airway during sleep leading to recurrent arousals, intermittent hypoxia, and surges in sympathetic activation
The Candidate Gene Association Resource (CARe) consortium included three cohorts with OSA phenotyping included in this analysis: the Cleveland Family Study (CFS) and subgroups of the Sleep Heart Health Study recruited from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study (FHS)
The substantial neurocognitive and cardiovascular morbidity attributed to OSA as well as the likely rising prevalence of this condition with the growing obesity epidemic make understanding the genetic basis for this disease an important priority
Summary
Obstructive sleep apnea (OSA) is a common disorder characterized by collapse of the upper airway during sleep leading to recurrent arousals, intermittent hypoxia, and surges in sympathetic activation. By narrowing the upper airway lumen, obesity is one of the strongest risk factors for OSA [1]. Numerous studies have established that OSA aggregates within families suggesting the presence of a genetic predisposition [8,9,10]. Those with one affected relative are approximately 50% more likely to have OSA themselves [8]. Though obesity itself has a strong genetic basis, the familial aggregation of OSA persists even after accounting for obesity [11]. The overall health impact of OSA and limited treatment options currently available for this disease underscore the need to better understand its molecular basis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
