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

oleh: Yuan Zhang, Michael Elgart, Nuzulul Kurniansyah, Brian W. Spitzer, Heming Wang, Doyoon Kim, Neomi Shah, Martha Daviglus, Phyllis C. Zee, Jianwen Cai, Daniel J. Gottlieb, Brian E. Cade, Susan Redline, Tamar Sofer

Format: Article
Diterbitkan: Elsevier 2022-10-01

Deskripsi

Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: There are shared genetic underpinnings of anthropometric, blood pressure, and glycaemic phenotypes with OSA, with evidence for causal relationships between some phenotypes. Funding: Described in Acknowledgments.