@article{29b6faec815049298d6ee00f1a22ba28,
title = "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, 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 = 1.90×10-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88×10-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P<5×10-7). 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.",
keywords = "GWAS, Genetics, Hypoxia, Prader-Willi syndrome, Sleep apnea",
author = "Cade, {Brian E.} and Han Chen and Stilp, {Adrienne M.} and Gleason, {Kevin J.} and Tamar Sofer and Sonia Ancoli-Israel and Raanan Arens and Bell, {Graeme I.} and Below, {Jennifer E.} and Bjonnes, {Andrew C.} and Sung Chun and Conomos, {Matthew P.} and Evans, {Daniel S.} and Johnson, {W. Craig} and Frazier-Wood, {Alexis C.} and Lane, {Jacqueline M.} and Larkin, {Emma K.} and Loredo, {Jose S.} and Post, {Wendy S.} and Ramos, {Alberto R.} and Ken Rice and Rotter, {Jerome I.} and Shah, {Neomi A.} and Stone, {Katie L.} and Taylor, {Kent D.} and Thornton, {Timothy A.} and Tranah, {Gregory J.} and Chaolong Wang and Zee, {Phyllis C.} and Hanis, {Craig L.} and Sunyaev, {Shamil R.} and Patel, {Sanjay R.} and Laurie, {Cathy C.} and Xiaofeng Zhu and Richa Saxena and Xihong Lin and Susan Redline",
note = "Funding Information: Supported by National Institutes of Health grants T32-HL007901-16 and R01-HL113338-04 (B.E.C.). The Sleep Reading Center of Brigham and Women's Hospital has been supported by National Institutes of Health grants 5-R01-HL046380-15 and 5-KL2-RR024990-05. Hispanic Community Health Study/Study of Latinos (HCHS/SOL): baseline examination of HCHS/SOL was performed as a collaborative study supported by contracts from the NHLBI to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes/centers/offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and National Institutes of Health Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and National Institute of Dental and Craniofacial Research contracts (HHSN268201300005C AM03 and MOD03). Provision of genotyping services supported in part by National Center for Advancing Translational Sciences (NCATS) CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DRC grant DK063491. Multi-Ethnic Study of Atherosclerosis (MESA): MESA is conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts 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, and DK063491. Funding for SHARe genotyping was provided by NHLBI contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, CA) and the Broad Institute of Harvard and Massachusetts Institute of Technology (Boston, MA). Funding support for the Sleep Polysomnography dataset was provided by grant HL56984. Provision of genotyping services supported in part by NCATS CTSI grant UL1TR000124 and NIDDK DRC grant DK063491. Starr County Health Studies (Starr): Starr is supported in part by grants R01 DK073541, U01 DK085501, R01 AI085014, and R01 HL102830 from the National Institutes of Health, and funds from the University of Texas Health Science Center at Houston. G.I.B. supported in part by grant P30 DK020595 and a gift from the Kovler Family Foundation. The Atherosclerosis Risk in Communities Study is conducted and supported by the NHLBI in collaboration with the 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), and University of Mississippi Medical Center (N01-HC-55021) Publisher Copyright: Copyright {\textcopyright} 2016 by the American Thoracic Society.",
year = "2016",
month = oct,
day = "1",
doi = "10.1164/rccm.201512-2431OC",
language = "English (US)",
volume = "194",
pages = "886--897",
journal = "American journal of respiratory and critical care medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "7",
}
