Genetic determinants of cardiometabolic and pulmonary phenotypes and obstructive sleep apnoea in HCHS/SOL
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
Affiliations
Yuan Zhang
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
Michael Elgart
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Nuzulul Kurniansyah
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Brian W. Spitzer
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Heming Wang
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Doyoon Kim
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Neomi Shah
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Martha Daviglus
Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA
Phyllis C. Zee
Center for Circadian and Sleep Medicine, Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
Jianwen Cai
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Daniel J. Gottlieb
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Brian E. Cade
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Susan Redline
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Tamar Sofer
Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Corresponding author at: Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.
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.
