Genetic determinants of cardiometabolic and pulmonary phenotypes and obstructive sleep apnoea in HCHS/SOL

• Published in: EBioMedicine Vol. 84; p. 104288
• Main Authors: Zhang, Yuan, Elgart, Michael, Kurniansyah, Nuzulul, Spitzer, Brian W., Wang, Heming, Kim, Doyoon, Shah, Neomi, Daviglus, Martha, Zee, Phyllis C., Cai, Jianwen, Gottlieb, Daniel J., Cade, Brian E., Redline, Susan, Sofer, Tamar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2022; Elsevier
• Subjects: Blood Glucose; Body Mass Index; Cardiometabolic and pulmonary phenotypes; Cardiovascular Diseases - complications; Cardiovascular Diseases - genetics; Genetic correlation; Genome-Wide Association Study; Glycated Hemoglobin; Humans; Insulin - genetics; Mendelian randomization; Obstructive sleep apnoea; Phenotype; Polygenic risk score; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - genetics; Polygenic risk score; Genetic correlation; Obstructive sleep apnoea; Cardiometabolic and pulmonary phenotypes; Mendelian randomization
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2022.104288

Obstructive Sleep Apnoea (OSA) often co-occurs with cardiometabolic and pulmonary diseases. This study is to apply genetic analysis methods to explain the associations between OSA and related phenotypes. In the Hispanic Community Healthy Study/Study of Latinos, we estimated genetic correlations ρg between the respiratory event index (REI) and 54 anthropometric, glycemic, cardiometabolic, and pulmonary phenotypes. We used summary statistics from published genome-wide association studies to construct Polygenic Risk Scores (PRSs) representing the genetic basis of each correlated phenotype (ρg>0.2 and p-value<0.05), and of OSA. We studied the association of the PRSs of the correlated phenotypes with both REI and OSA (REI≥5), and the association of OSA PRS with the correlated phenotypes. Causal relationships were tested using Mendelian Randomization (MR) analysis. The dataset included 11,155 participants, 31.03% with OSA. 22 phenotypes were genetically correlated with REI. 10 PRSs covering obesity and fat distribution (BMI, WHR, WHRadjBMI), blood pressure (DBP, PP, MAP), glycaemic control (fasting insulin, HbA1c, HOMA-B) and insomnia were associated with REI and/or OSA. OSA PRS was associated with BMI, WHR, DBP and glycaemic traits (fasting insulin, HbA1c, HOMA-B and HOMA-IR). MR analysis identified robust causal effects of BMI and WHR on OSA, and probable causal effects of DBP, PP, and HbA1c on OSA/REI. There are shared genetic underpinnings of anthropometric, blood pressure, and glycaemic phenotypes with OSA, with evidence for causal relationships between some phenotypes. Described in Acknowledgments.