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Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.

TitleGenetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.
Publication TypePublication
Year2016
AuthorsCade BE, Chen H, Stilp AM, Gleason KJ, Sofer T, Ancoli-Israel S, Arens R, Bell GI, Below JE, Bjonnes AC, Chun S, Conomos MP, Evans DS, W Johnson C, Frazier-Wood AC, Lane JM, Larkin EK, Loredo JS, Post WS, Ramos AR, Rice K, Rotter JI, Shah NA, Stone KL, Taylor KD, Thornton TA, Tranah GJ, Wang C, Zee PC, Hanis CL, Sunyaev SR, Patel SR, Laurie CC, Zhu X, Saxena R, Lin X, Redline S
JournalAm J Respir Crit Care Med
Volume194
Issue7
Pagination886-897
Date Published2016 Oct 01
ISSN1535-4970
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 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10). 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.

DOI10.1164/rccm.201512-2431OC
Alternate JournalAm J Respir Crit Care Med
PubMed ID26977737
PubMed Central IDPMC5074655
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
R01 DK073541 / DK / NIDDK NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
KL2 RR024990 / RR / NCRR NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
U01 DK085501 / DK / NIDDK NIH HHS / United States
P50 HL056984 / HL / NHLBI NIH HHS / United States
R35 CA197449 / CA / NCI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
KL2 TR000461 / TR / NCATS NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
K23 HL125923 / HL / NHLBI NIH HHS / United States
T32 HL007901 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
R03 HL140273 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
U54 HD083211 / HD / NICHD NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 HL102830 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
UL1 TR001073 / TR / NCATS NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
R01 AI085014 / AI / NIAID NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
MS#: 
0186
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Baseline Visit - Sleep Center - Harvard Medical School/The Brigham & Women's Hospital
ECI: 
Yes
Manuscript Status: 
Published