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Research Project: Childhood Obesity Prevention

Location: Children's Nutrition Research Center

Title: Genetic associations with obstructive sleep apnea traits in Hispanic/Latino Americans

Author
item CADE, BRIAN - Harvard Medical School
item CHEN, HAN - Harvard School Of Public Health
item STILP, ADRIENNE - University Of Washington
item GLEASON, KEVIN - Harvard Medical School
item SOFER, TAMAR - University Of Washington
item ANCOLI-ISRAEL, SONIA - University Of California
item ARENS, RAANAN - Albert Einstein College Of Medicine
item BELL, GRAEME - University Of Chicago
item BELOW, JENNIFER - University Of Texas Health Science Center
item BJONNES, ANDREW - Brigham & Women'S Hospital
item CHUN, SUNG - Brigham & Women'S Hospital
item CONOMOS, MATTHEW - University Of Washington
item EVANS, DANIEL - California Pacific Medical Center
item JOHNSON, W - University Of Washington
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item LANE, JACQUELINE - Massachusetts General Hospital
item LARKIN, EMMA - Vanderbilt University Medical Center
item LOREDO, JOSE - University Of California
item POST, WENDY - Johns Hopkins University
item RAMOS, ALBERTO - University Of Miami
item RICE, KEN - University Of Washington
item ROTTER, JEROME - Harbor-Ucla Medical Center
item SHAH, NEOMI - Albert Einstein College Of Medicine
item STONE, KATIE - California Pacific Medical Center
item TAYLOR, KENT - Harbor-Ucla Medical Center
item THORNTON, TIMOTHY - University Of Washington
item TRANAH, GREGORY - California Pacific Medical Center
item WANG, CHAOLONG - Harvard School Of Public Health
item ZEE, PHYLLIS - Northwestern University
item HANIS, CRAIG - University Of Texas Health Science Center
item SUNYAEV, SHAMIL - Brigham & Women'S Hospital
item PATEL, SANJAY - Beth Israel Deaconess Medical Center
item LAURIE, CATHY - University Of Washington
item ZHU, XIOFENG - Case Western Reserve University (CWRU)
item SAXENA, RICHA - Massachusetts General Hospital
item LIN, XIHONG - Harvard School Of Public Health
item REDLINE, SUSAN - Beth Israel Deaconess Medical Center

Submitted to: American Journal of Respiratory and Critical Care Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2016
Publication Date: 10/1/2016
Citation: Cade, B.E., Chen, H., Stilp, A.M., Gleason, K.J., Sofer, T., Ancoli-Israel, S., Arens, R., Bell, G.I., Below, J.E., Bjonnes, A.C., Chun, S., Conomos, M.P., Evans, D.S., Johnson, W.C., Frazier-Wood, A.C., Lane, J.M., Larkin, E.K., Loredo, J.S., Post, W.S., Ramos, A.R., Rice, K., Rotter, J.I., Shah, N.A., Stone, K.L., Taylor, K.D., Thornton, T.A., Tranah, G.J., Wang, C., Zee, P.C., Hanis, C.L., Sunyaev, S.R., Patel, S.R., Laurie, C.C., Zhu, X., Saxena, R., Lin, X., Redline, S. 2016. Genetic associations with obstructive sleep apnea traits in Hispanic/Latino Americans. American Journal of Respiratory and Critical Care Medicine. 194(7):886-897.

Interpretive Summary: Obstructive Sleep Apnea (OSA) is a condition where breathing temporarily stops when asleep. OSA is associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Hispanics are at a higher risk for diabetes and cardiovascular disease, and in Hispanics the genetic basis of OSA is still largely unknown. We identified nine new genetic variants associated with OSA. The variants identified were in genes with inflammatory, hypoxia signaling and sleep related functions. We now better understand why some people have periods of OSA and will eventually use this information to help understand why this condition occurs.

Technical Abstract: 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. 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. 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. 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. 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