期刊
EUROPEAN RESPIRATORY JOURNAL
卷 57, 期 5, 页码 -出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/13993003.03091-2020
关键词
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资金
- Academy of Finland Center of Excellence in Complex Disease Genetics [312062, 312074]
- Academy of Finland [285380, 128650, 309643]
- Finnish Foundation for Cardiovascular Research
- Sigrid Juselius Foundation
- University of Helsinki HiLIFE
- Horizon 2020 Research and Innovation Programme [667301]
- Oskar Offlund Foundation
- Yrjo Jahnsson Foundation
- Finnish Dental Society Apollonia
- Business Finland [HUS 4685/31/2016, UH 4386/31/2016]
- AbbVie Inc.
- AstraZeneca UK Ltd
- Biogen MA Inc.
- Celgene Corp.
- Celgene International II Sarl
- Genentech Inc.
- Merck Sharp Dohme Corp.
- Pfizer Inc.
- GSK
- Sanofi
- Maze Therapeutics Inc.
- Janssen Biotech Inc.
- Academy of Finland (AKA) [285380, 285380, 312074, 309643, 309643, 312074] Funding Source: Academy of Finland (AKA)
- H2020 Societal Challenges Programme [667301] Funding Source: H2020 Societal Challenges Programme
This study identified five genetic loci associated with OSA risk and found high genetic correlations between OSA and comorbidities such as obesity. The findings support a causal link between obesity and OSA, indicating a joint genetic basis between OSA and related health conditions.
There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217955 individuals) with 16761 OSA patients identified using nationwide health registries. We estimated 0.08 (95% CI 0.06-0.11) heritability and identified five loci associated with OSA (p < 5.0x10(-8)): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains 1), rs10928560 near CXCR4 (C-X-C motif chemokine receptor type 4), rs185932673 near CAMK1D (calcium/calmodulindependent protein kinase ID) and rs9937053 near FTO (fat mass and obesity-associated protein; a variant previously associated with body mass index (BMI)). In a BMI-adjusted analysis, an association was observed for rs10507084 near RMST/NEDD1 (rhabdomyosarcoma 2 associated transcript/NEDD1 gamma tubulin ring complex targeting factor). We found high genetic correlations between OSA and BMI (r(g)=0.72 (95% CI 0.62-0.83)), and with comorbidities including hypertension, type 2 diabetes, coronary heart disease, stroke, depression, hypothyroidism, asthma and inflammatory rheumatic disease (rg > 0.30). The polygenic risk score for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile, and Mendelian randomisation supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA, and the joint genetic basis between OSA and comorbidities.
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