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

EBioMedicine. 2022 Oct:84:104288. doi: 10.1016/j.ebiom.2022.104288. Epub 2022 Sep 26.


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.

Keywords: Cardiometabolic and pulmonary phenotypes; Genetic correlation; Mendelian randomization; Obstructive sleep apnoea; Polygenic risk score.

MeSH terms

  • Blood Glucose
  • Body Mass Index
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / genetics
  • Genome-Wide Association Study
  • Glycated Hemoglobin
  • Humans
  • Insulin / genetics
  • Phenotype
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / genetics


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin