LAUSR

RATIONALE Craniofacial and pharyngeal morphology are risk factors for Obstructive Sleep Apnea (OSA). Quantitative photography provides phenotypic information about these anatomic risk factors and is feasible in large samples. However, whether associations between morphology and OSA severity are influenced by genetic ancestry is unknown. OBJECTIVE The aim of this study was to examine this question in a large sample encompassing people from distinct ancestral backgrounds. METHODS Participants of the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) cohort with available genomic data were included (N=2,393). Associations between photography-based measures and OSA severity were assessed using linear regression models, controlling for age, sex, and BMI. Statistical interaction tests were used to assess if genetically-determined ancestry (based on 1000 Genomes reference populations) influenced the relationship of anatomy with OSA severity. RESULTS Cluster analysis of genetic ancestry proportions identified four ancestry groups: East Asian (48.3%), European (33.6%), Mixed (11.7%) and African (6.4%). Multiple anatomic traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized β [95%CI] = 0.11 [0.06, 0.16], p<0.001), mandibular width (0.15 [0.10, 0.20], p<0.001), and tongue thickness (0.06 [0.02, 0.10], p=0.001) and smaller airway width (-0.08 [-0.15, -0.002]). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated stronger/weaker associations with OSA severity based on genetic ancestry. CONCLUSIONS We confirm multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, while others differ in their association.