Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring.

Autor:	Campos AI; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia., Ingold N; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia., Huang Y; 23andMe, Inc., Sunnyvale, CA, USA., Mitchell BL; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Kho PF; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA., Han X; Program in Genetic Epidemiology and Statistical Genetics, Harvard University T.H. Chan School of Public Health, Boston, MA, USA., García-Marín LM; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Ong JS; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Law MH; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia., Yokoyama JS; Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.; Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Martin NG; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Dong X; Genomics and Bioinformatics Hub, Brigham and Women's Hospital, Boston, MA, USA.; Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Cuellar-Partida G; 23andMe, Inc., Sunnyvale, CA, USA., MacGregor S; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Aslibekyan S; 23andMe, Inc., Sunnyvale, CA, USA., Rentería ME; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Sleep [Sleep] 2023 Mar 09; Vol. 46 (3).
DOI:	10.1093/sleep/zsac308
Abstrakt:	Study Objectives: Despite its association with severe health conditions, the etiology of sleep apnea (SA) remains understudied. This study sought to identify genetic variants robustly associated with SA risk. Methods: We performed a genome-wide association study (GWAS) meta-analysis of SA across five cohorts (NTotal = 523 366), followed by a multi-trait analysis of GWAS (multi-trait analysis of genome-wide association summary statistics [MTAG]) to boost power, leveraging the high genetic correlation between SA and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional and joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal = 1 477 352; Ncases = 175 522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. Results: Our SA meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with SA risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. Conclusion: Our study uncovered multiple genetic loci associated with SA risk, thus increasing our understanding of the etiology of this condition and its relationship with other complex traits. (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)
Databáze:	MEDLINE
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