Multivariate genetic architecture of poor sleep quality

Qihao WangLuqi GaoXiaoshan YangBo Chen^*Wenchen Li^*Haifeng Wang^*

• The Second Hospital of Jilin University, Changchun, China

The field of genetics has yet to elucidate the complex genetic underpinnings that influence sleep quality. Previous studies have conducted genome-wide association studies (GWAS) on different dimensions of sleep health, but have not directly analyzed the multivariate genetic structure of poor sleep quality (PSQ). To address this knowledge gap, we employed a multifaceted approach that incorporated Genomic Structural Equation Modeling (Genomic-SEM) and multiple Post-GWAS methods. This strategy enabled us to identify causal single nucleotide polymorphisms (SNPs) that contribute to the variability in poor sleep quality. Our study identified a total of 14 leading SNP loci (such as rs2820309) and 3 fine-mapping significant loci (such as KTN1: rs77168063). To further investigate the underlying mechanisms, we employed multiple whole-transcriptome association methods. These methods analyzed susceptible gene signal loci that exhibited strong correlation with poor sleep quality, as determined by tissue, cell layer, and genome component analysis, along with related component information. Subsequently, data on approximately 13,000 common diseases were evaluated to determine the associated predisposing factors for poor sleep quality, and the correlation between poor sleep quality and 20 common neurological diseases was assessed. Additionally, we utilized a polygenic score based on summary data to analyze evidence of risk for poor sleep quality across different chromosomes. This study offers a novel perspective on the genetic underpinnings of poor sleep quality by conducting a genome-wide association study for a phenotype that was not directly measured.