Dataset Information

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

ABSTRACT:

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 ρ_g 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 (ρ_g>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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9515437 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Yuan Y Elgart Michael M Kurniansyah Nuzulul N Spitzer Brian W BW Wang Heming H Kim Doyoon D Shah Neomi N Daviglus Martha M Zee Phyllis C PC Cai Jianwen J Gottlieb Daniel J DJ Cade Brian E BE Redline Susan S Sofer Tamar T

EBioMedicine 20220926

<h4>Background</h4>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.<h4>Methods</h4>In the Hispanic Community Healthy Study/Study of Latinos, we estimated genetic correlations ρ<sub>g</sub> between the respiratory event index (REI) and 54 anthropometric, glycemic, cardiometabolic, and pulmonary phenotypes. We used summary statistics from publis ...[more]

PMID: 36174398

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Project description:The roles of central nervous mechanisms and cortical output in obstructive sleep apnoea remain unclear. We addressed corticomuscular coupling between cortical sensorimotor areas and lower facial motor units as a mechanistic pathway and as a possible surrogate marker of corticoperipheral motor control in obstructive sleep apnoea. In this exploratory cross-sectional retrospective study, we analysed EEG (C3 and C4 leads) and chin EMG from polysomnography recordings in 86 participants (22 females; age range: 26-81 years): 27 with mild (respiratory disturbance index = 5-15 events/h), 21 with moderate (15-30 events/h) and 23 with severe obstructive sleep apnoea (>30 events/h) and 15 control subjects (<5 events/h). By computing C3-/C4-EEG-chin EMG coherence of signal dynamics in time and frequency domains, we investigated corticomuscular coupling between cortical sensorimotor areas and lower facial motor units with increasing obstructive sleep apnoea severity during the entire sleeping time, during different sleep stages and during obstructive respiratory events, including 5 s before (stable breathing) and after events (breathing resumption). In addition, we studied a possible influence of body mass index and autonomic nervous system activation. We found that both average and respiratory event-specific corticomuscular coupling between cortical sensorimotor areas and lower facial motor units weakened significantly with increasing obstructive sleep apnoea severity, was strongest during N3 and weakened in N1, N2 and rapid eye movement stages (in decreasing order). Coupling increases significantly during the obstructive respiratory events compared with coupling just before and following them. Results were independent of body mass index or autonomic nervous system activation. We conclude that obstructive respiratory events in obstructive sleep apnoea are very strongly associated both quantitatively and temporally with the degree of disconnection within the cortical sensorimotor areas-lower facial motor units pathway. This quite coordinated activity pattern suggests a cortical sensorimotor area-driven obstructive respiratory event pattern generator and a central motor output disorder in obstructive sleep apnoea.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

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