期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 194, 期 7, 页码 886-897出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201512-2431OC
关键词
sleep apnea; hypoxia; genetics; GWAS; Prader-Willi syndrome
资金
- National Institutes of Health [T32-HL007901-16, R01-HL113338-04, 5-R01-HL046380-15, 5-KL2-RR024990-05, R01 DK073541, U01 DK085501, R01 AI085014, R01 HL102830]
- NHLBI [N01-HC65233, N02-HL-64278]
- University of Miami [N01-HC65234]
- Albert Einstein College of Medicine [N01-HC65235]
- Northwestern University [N01-HC65236]
- San Diego State University [N01-HC65237]
- National Institute of Dental and Craniofacial Research [HHSN268201300005C AM03, MOD03]
- National Center for Advancing Translational Sciences (NCATS) CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DRC grant [DK063491]
- NCATS CTSI [UL1TR000124]
- NIDDK DRC [DK063491]
- Kovler Family Foundation [P30 DK020595]
- University of North Carolina [N01-HC-55015, N01-HC-55018]
- Baylor College of Medicine [N01-HC-55016]
- University of Minnesota [N01-HC-55019]
- Johns Hopkins University [N01-HC-55020]
- University of Mississippi Medical Center [N01-HC-55021]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-001079]
- [UL1-TR-000040]
- [HL56984]
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, Multi Ethnic 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 X 10(-8) for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 X 10(-8) for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 X 10(-7)). 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.
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