Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Abstract

Rationale: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.Objectives: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.Methods: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, MultiEthnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.Measurements and Main Results: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 3 10 28 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 3 10 28 for respiratory event duration) and seven additional loci were identified with suggestive significance (P , 5 3 10 27 ). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility.Conclusions: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

Genetic Influences on Evening Preference Overlap with Those for Bipolar Disorder in a Sample of Mexican Americans and American Indians

“…The results of several Genome-Wide Association Studies (GWAS) on sleep duration, sleep latency, sleep depth, sleep quality, insomnia, daytime sleepiness, sleep apnea, and actigraphic measurements are available (Allebrandt et al, 2013; Amin et al, 2016; Byrne et al, 2013; Cade, Chen, et al, 2016; Cade, Gottlieb, et al, 2016; Gottlieb et al, 2015; Gottlieb et al, 2007; Lane et al, 2017; Marinelli et al, 2016; Ollila et al, 2014; Scheinfeldt et al, 2015; Spada et al, 2016), yet many of these phenotypes are independent of chronotype (Jones et al, 2016; Lane et al, 2017; Lehnkering & Siegmund, 2007). Two early GWAS identified several single nucleotide polymorphisms (SNPs) associated with the chronotype measure bedtime.…”

“…While these studies have shed light onto the molecular basis of diurnal preference in human populations, they have solely looked at populations of European ancestry. Several GWAS on sleep phenotypes have included subjects of diverse ethnic background (Cade, Gottlieb, et al, 2016; Scheinfeldt et al, 2015), including a solely Hispanic sample (Cade, Chen, et al, 2016), yet these studies did not assess chronotype.…”

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos

“…For imputed SNPs, we calculated the imputation quality scores "info" and "oevar" (ratio of observed to expected variance of imputed dosage) for each SNP and excluded SNPs with oevar <0.3 (Li et al 2010). Finally, SNPs with 50 or fewer counts of the expected or effective number of copies (effN) of the minor allele were excluded from analysis (Cade et al 2016). A variant's effN is approximately its minor allele count and was estimated as 2 × MAF × (1−MAF) × N × oevar, where MAF is the frequency of the minor allele, N is the number of participants, and oevar is set to 1 for genotyped variants.…”

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

“…The molecular mechanisms underlying OSA remain unclear, and could be mediated, in part, by OSA-induced genes. In this regard, Cade and coworkers (2016) carried out GWAS in 12,558 Hispanic subjects finding two novel loci at genome level with significance for apnea-hypopnea index [31].…”