Jia Ningning, Zhu Zhenhua, Liu Yane, Yin Xuyuan, Man Lijuan, Hou Wenlong, Zhang Huiping, Yu Qiong, Hui Li
Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China.
Research Center of Biological Psychiatry, Suzhou Guangji Hospital, Suzhou Medical College of Soochow University, Suzhou, China.
Sleep. 2025 Jan 13;48(1). doi: 10.1093/sleep/zsae209.
Sleep disorders and psychiatric disorders frequently coexist and interact, yet the shared genetic basis linking these two domains remains poorly understood.
We investigated the genetic correlation and overlap between seven sleep/circadian traits and three psychiatric disorders at the level of genome-wide association studies (GWAS), utilizing LDSC, HDL, and GPA. To identify potential polygenic single nucleotide variations (SNVs) within each trait pair, we used PLACO, while gene-level analyses were performed using MAGMA and POPS. Furthermore, the functions and biological mechanisms, enriched phenotypes, tissues, cellular features, and pathways were thoroughly investigated using FUMA, deTS, and enrichment analyses at the biological pathway level.
Our study revealed extensive genetic associations and overlaps in all 21 trait pairs. We identified 18 494 SNVs and 543 independent genomic risk loci, with 113 confirmed as causative through colocalization analysis. These loci collectively spanned 196 unique chromosomal regions. We pinpointed 43 distinct pleiotropic genes exhibiting significant enrichment in behavioral/physiological phenotypes, nervous system phenotypes, and brain tissue. Aberrations in synaptic structure and function, neurogenesis and development, as well as immune responses, particularly involving the MAPK pathway, emerged as potential underpinnings of the biology of sleep/circadian traits and psychiatric disorders.
We identified shared loci and specific sets of genes between sleep/circadian traits and psychiatric disorders, shedding light on the genetic etiology. These discoveries hold promise as potential targets for novel drug interventions, providing valuable insights for the development of therapeutic strategies for these disorders.
睡眠障碍和精神障碍经常共存并相互影响，但连接这两个领域的共同遗传基础仍知之甚少。
我们在全基因组关联研究（GWAS）层面，利用LDSC、HDL和GPA，研究了七种睡眠/昼夜节律特征与三种精神障碍之间的遗传相关性和重叠性。为了识别每个特征对中的潜在多基因单核苷酸变异（SNV），我们使用了PLACO，而基因水平分析则使用MAGMA和POPS进行。此外，还使用FUMA、deTS和生物途径水平的富集分析，对功能和生物学机制、富集表型、组织、细胞特征和途径进行了深入研究。
我们的研究揭示了所有21个特征对中广泛的遗传关联和重叠。我们识别出18494个SNV和543个独立的基因组风险位点，其中113个通过共定位分析被确认为致病位点。这些位点共同跨越196个独特的染色体区域。我们确定了43个不同的多效性基因，这些基因在行为/生理表型、神经系统表型和脑组织中表现出显著富集。突触结构和功能、神经发生和发育以及免疫反应的异常，特别是涉及丝裂原活化蛋白激酶（MAPK）途径的异常，成为睡眠/昼夜节律特征和精神障碍生物学的潜在基础。
我们识别出了睡眠/昼夜节律特征与精神障碍之间的共享位点和特定基因集，为遗传病因学提供了线索。这些发现有望成为新型药物干预的潜在靶点，为这些疾病治疗策略的开发提供有价值的见解。
