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Sleep apnea is the manifestation of key "endotypic traits" including greater pharyngeal collapsibility, reduced dilator muscle compensation and elevated chemoreflex loop gain.We investigate how endotypic traits vary with obesity, age, sex, and race/ethnicity to influence sleep apnea disease severity (apnea-hypopnea index, AHI).Endotypic traits were estimated from polysomnography in a diverse community-based cohort study (Multi-Ethnic Study of Atherosclerosis, N=1971, age: 54-93yr). Regression models assessed associations between each exposure (continuous variables per 2SD) and endotypic traits (per SD) or AHI (events/h), independent of other exposures. Generalizability was assessed in two independent cohorts.Greater AHI was associated with obesity (+19 events/h per 11 kg/m2 [2SD]), male sex (+13 events/h v. female), older age (+7 events/h per 20 yr), and Chinese ancestry (+5 events/h v. White, nb. obesity adjusted). Obesity-related increase in AHI was best explained by elevated collapsibility (+0∙40 SD) and greater loop gain (+0∙38 SD; percentage mediated=26[95% CI: 20-32] %). Male-related increase in AHI was explained by elevated collapsibility (+0∙86 SD) and reduced compensation (-0∙40 SD; percentage mediated=57[50-66] %). Age-related AHI increase was explained by elevated collapsibility (+0∙37 SD) and greater loop gain (+0∙15 SD; percentage mediated=48[34-63] %). Increased AHI with Chinese ancestry was explained by collapsibility (+0∙57 SD; percentage mediated=87[57-100] %). Black race was associated reduced collapsibility (-0∙30 SD) and elevated loop gain (+0∙29 SD). Similar patterns were observed in the other cohorts.Different subgroups exhibit different underlying pathophysiological pathways to sleep apnea, highlighting the variability in mechanisms that could be targeted for intervention.

Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypo...

Rationale: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea–hypopnea index (AHI). Respiratory event duration is a he...

Rationale: Sleep disorders are associated with hypertension and diabetes, which are primary risk factors for cardiovascular diseases and mortality. It is important to understand these associations ...

Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEVWe identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10 -8 ) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.