Abstract
There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed at identifying 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 FinnGen Study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries.
We estimated 8.3% [0.06–0.11] heritability and identified five loci associated with OSA (p<5.0×10−8): rs4837016 near GTPase activating protein and VPS9 domains 1 (GAPVD1), rs10928560 near C-X-C motif chemokine receptor 4 (CXCR4), rs185932673 near Calcium/calmodulin-dependent protein kinase ID (CAMK1D) and rs9937053 near Fat mass and obesity-associated protein (FTO) - a variant previously associated with body mass index (BMI). In a BMI-adjusted analysis, an association was observed for rs10507084 near Rhabdomyosarcoma 2 associated transcript (RMST)/NEDD1 gamma-tubulin ring complex targeting factor (NEDD1). We found high genetic correlations between OSA and BMI (rg=0.72 [0.62–0.83]) and with comorbidities including hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), stroke, depression, hypothyroidism, asthma and inflammatory rheumatic diseases (IRD) (rg>0.30). Polygenic risk score (PRS) 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 joint genetic basis between OSA and comorbidities.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Strausz has nothing to disclose.
Conflict of interest: Dr. Ruotsalainen has nothing to disclose.
Conflict of interest: Dr. Ollila has nothing to disclose.
Conflict of interest: Dr. Karjalainen has nothing to disclose.
Conflict of interest: Dr. Kiiskinen has nothing to disclose.
Conflict of interest: Dr. Reeve has nothing to disclose.
Conflict of interest: Dr. Kurki has nothing to disclose.
Conflict of interest: Dr. Mars has nothing to disclose.
Conflict of interest: Dr. Havulinna has nothing to disclose.
Conflict of interest: Dr. Luonsi has nothing to disclose.
Conflict of interest: Dr. Mansour Aly has nothing to disclose.
Conflict of interest: Dr. Ahlqvist has nothing to disclose.
Conflict of interest: Dr. Teder-Laving has nothing to disclose.
Conflict of interest: Dr. Palta has nothing to disclose.
Conflict of interest: Dr. Groop has nothing to disclose.
Conflict of interest: Dr. Mägi has nothing to disclose.
Conflict of interest: Dr. Mäkitie has nothing to disclose.
Conflict of interest: Dr. Salomaa reports grants from Novo Nordisk and Sanofi for consultations and has ongoing research collaboration with Bayer AG, outside the submitted work;.
Conflict of interest: Dr. Bachour has nothing to disclose.
Conflict of interest: Dr. Tuomi has nothing to disclose.
Conflict of interest: Dr. Palotie has nothing to disclose.
Conflict of interest: Dr. Palotie has nothing to disclose.
Conflict of interest: Dr. Ripatti has nothing to disclose.
- Received August 10, 2020.
- Accepted November 4, 2020.
- Copyright ©ERS 2020
LIBRARY USERS
Log in through your institution
Purchase access
