Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals

作者：Huajun Xu, Feng Liu, Zhiqiang Li, Xinyi Li, Yuenan Liu, Niannian Li, Xiaoxu Zhang, Zhenfei Gao, Xiaoman Zhang, Yupu Liu, Jianyin Zou, Lili Meng, Suru Liu, Huaming Zhu, Xulan Tang, Hongmin Wu, K. X. Su, Bin Chen, Dongzhen Yu, Haibo Ye, Haoyan Chen, Hongliang Yi, Shankai Yin, Jian Guan, Yongyong Shi · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2022 · DOI：10.1164/rccm.202109-2044oc · 被引用次数：53 · 研究领域：Obstructive Sleep Apnea Research、Neuroscience of respiration and sleep、Sleep and related disorders

Abstract Rationale Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results Two characteristic study-wide significant loci (P < 2.63 × 10−9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39–1.89; P = 6.98 × 10−10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79–0.88; P = 7.57 × 10−10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions We identified ...