0004 GENOME-WIDE ASSOCIATION STUDY FOR SNORING IDENTIFIES NOVEL GENETIC FACTORS AND BIOLOGICAL LINKS TO SLEEP APNEA AND OBESITY

Abstract

Introduction: Snoring is a common condition, affecting roughly 90 million adults in the U.S. Snoring is associated with lower sleep quality, strain on the heart, low blood oxygen levels, obesity, and chronic headaches. Although lifestyle factors play a role, a familial history of snoring increases snoring risk 3-fold. Identifying the genetic basis for snoring should lead to a better understanding of the factors that control breathing during sleep and causal relationships with disease outcomes. Methods: We performed genome-wide association analyses of self-reported snoring in >100,000 subjects of European ancestry in the UK Biobank. We measured heritability and performed association tests adjusting for age, sex, body mass index, genetic ancestry and genotyping array (>39 million variants). We performed follow-up analysis stratified by sex or obesity status. Pair-wise genetic correlation analyses to 19 traits, including sleep apnea, were also performed. Results: We identified three genome-wide suggestive (p<5x10-7) loci associated with snoring (near FBXL4, GALNT12/COL15A1 and NPLOC4). In analyses stratified by obesity status, we identified suggestive association with an increased risk of snoring in obese subjects only (rs183549235 A allele: BMI<30 (p=0.56); BMI≥30, OR [95%CI] 2.14 [1.60-2.85], p= 2.04 x10-7; pinteraction=1.05 x10-6) and a second locus with suggestive association to increased risk of snoring in non-obese subjects only (rs550052742 C allele, BMI<30, OR [95%CI] 1.44 [1.26-1.65], p= 1.18 x10-7; BMI≥30, p= 0.10; pinteraction= 3.28 x10-5). We also found a sex specific locus conferring an increased risk of snoring in females only (rs138233508 T allele, Females OR [95%CI] 1.23 [1.14-1.33], p=1.74 x10-7; Male p=0.59; pinteraction=1.35 x10-4). Lastly, we tested for traits with a significant biological link to snoring. Significant genetic correlation was observed between snoring and obstructive sleep apnea (rg=0.55, p=5.59 x10-4), BMI (rg=0.20, p=9.15 x10-7), anorexia nervosa (rg= -0.37, p=1.44 x10-5), and years of education (rg= -0.27, p=2.03 x10-5). Conclusion: These results provide initial biological insights into the genetics of snoring and reveal shared underlying biology with health and disease.