Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

Abstract

There is currently only limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). The aim of our study is 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 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 < 5.0x10^-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 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 randomization 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.

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

“…As a proof-of-principle of the utility of having well-powered GWAS summary statistics, we performed a hypothesis-free inference of causal associations between >400 traits and our sleep apnoea MTAG. Consistent with previous findings 45 , our approach inferred obesity to likely increase the risk for sleep apnoea. Similar results were found for asthma, lung cancer, hernia, hypertension, ever having a period of mania and stroke.…”

Sleep apnoea is a risk factor for severe COVID-19

“…Of all patients with COVID-19 diagnosis (N=305, 38% male, mean age 55.2 years) 26 patients also had OSA diagnosis (8.5%, 46.2% male, mean age 63.0), (Table 1, Table 2). This reflects a similar prevalence of OSA diagnoses in COVID-19 infected as in the normal population in FinnGen, where prevalence is 8% 15 . 83 patients required hospitalization (38.6% male, mean age 66.3 years) including 16 OSA patients.…”

Association between depression and sleep apnoea: a Mendelian randomisation study

“…Third, we attempted to examine the relationship between sleep apnoea and depression in a population using MR. However, studies have reported sleep apnoea heritability estimates of 8.3% (0.06-0.11), whereas there are only five SNPs associated with sleep apnoea (P < 5.0 × 10 −8 ), including three SNPs in UK Biobank [44].…”