Abstract
PURPOSE: The reciprocal comorbidity of obstructive sleep apnea (OSA) and body mass index (BMI) has been observed, yet the shared genetic architecture between them remains unclear. This study aimed to explore the genetic overlaps between them. METHODS: Summary statistics were acquired from the genome-wide association studies (GWASs) on OSA (N(case) = 41,704; N(control) = 335,573) and BMI (N(overall) = 461,460). A comprehensive genome-wide cross-trait analysis was performed to quantify global and local genetic correlation, infer the bidirectional causal relationships, detect independent pleiotropic loci, and investigate potential comorbid genes. RESULTS: A positive significant global genetic correlation between OSA and BMI was observed (r (g) = 0.52, P = 2.85e-122), which was supported by three local signal. The Mendelian randomization analysis confirmed bidirectional causal associations. In the meta-analysis of cross-traits GWAS, a total of 151 single-nucleotide polymorphisms were found to be pleiotropic between OSA and BMI. Additionally, we discovered that the genetic association between OSA and BMI is concentrated in 12 brain regions. Finally, a total 134 expression-tissue pairs were observed to have a significant impact on both OSA and BMI within the specified brain regions. CONCLUSION: Our comprehensive genome-wide cross-trait analysis indicates a shared genetic architecture between OSA and BMI, offering new perspectives on the possible mechanisms involved.