Dataset Information

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?

SUBMITTER: Cade BE

PROVIDER: S-EPMC5074655 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Cade Brian E BE Chen Han H Stilp Adrienne M AM Gleason Kevin J KJ Sofer Tamar T Ancoli-Israel Sonia S Arens Raanan R Bell Graeme I GI Below Jennifer E JE Bjonnes Andrew C AC Chun Sung S Conomos Matthew P MP Evans Daniel S DS Johnson W Craig WC Frazier-Wood Alexis C AC Lane Jacqueline M JM Larkin Emma K EK Loredo Jose S JS Post Wendy S WS Ramos Alberto R AR Rice Ken K Rotter Jerome I JI Shah Neomi A NA Stone Katie L KL Taylor Kent D KD Thornton Timothy A TA Tranah Gregory J GJ Wang Chaolong C Zee Phyllis C PC Hanis Craig L CL Sunyaev Shamil R SR Patel Sanjay R SR Laurie Cathy C CC Zhu Xiaofeng X Saxena Richa R Lin Xihong X Redline Susan S

American journal of respiratory and critical care medicine 20161001 7

<h4>Rationale</h4>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 d ...[more]

PMID: 26977737

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Project description:BackgroundMetabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors.MethodsWe characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling.ResultsWe identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels.ConclusionsThe genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers.ImpactThis study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Dataset Information

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

Publications

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

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