Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Jiao Tong University, Shanghai 200240, China.
Genes (Basel). 2024 Jun 12;15(6):769. doi: 10.3390/genes15060769.
Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386,577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method, alongside a Bonferroni correction (( < 2.4 × 10) to determine significant causal associations. We further applied Cochran's Q statistical analysis, MR-Egger intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) for heterogeneity and pleiotropy assessment. IVW estimates revealed 79 potential causal effects of microbial taxa and pathways on sleep-related traits and 45 inverse causal relationships, with over half related to pathways, emphasizing their significance. The results revealed two significant causal associations: genetically determined relative abundance of pentose phosphate decreased sleep duration ( = 9.00 × 10), and genetically determined increase in fatty acid level increased the ease of getting up in the morning ( = 8.06 × 10). Sensitivity analyses, including heterogeneity and pleiotropy tests, as well as a leave-one-out analysis of single nucleotide polymorphisms, confirmed the robustness of these relationships. This study explores the potential causal relationships between sleep and microbial taxa and pathways, offering novel insights into their complex interplay.
最近的研究强调了睡眠与微生物分类群和途径之间的关联。然而，这些关联的因果效应仍然未知。为了研究这一点，我们使用来自 412 种肠道微生物组特征（N=7738）和七个与睡眠相关的特征（N=345552 至 386577）的全基因组关联研究（GWAS）汇总统计数据进行了双向两样本孟德尔随机化（MR）分析。我们采用了多种 MR 方法来评估因果关系，以逆方差加权（IVW）作为主要方法，同时进行 Bonferroni 校正（<2.4×10-2 以确定显著的因果关联。我们进一步应用 Cochran's Q 统计分析、MR-Egger 截距和 Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) 进行异质性和多效性评估。IVW 估计显示了 79 种微生物分类群和途径对睡眠相关特征的潜在因果影响，以及 45 种反向因果关系，其中超过一半与途径有关，强调了它们的重要性。结果揭示了两个具有统计学意义的因果关联：戊糖磷酸途径的遗传决定相对丰度降低了睡眠时间（β=9.00×10-3，SE=2.47×10-3），而脂肪酸水平的遗传增加增加了早晨起床的轻松程度（β=8.06×10-3，SE=2.47×10-3）。包括异质性和多效性测试以及单核苷酸多态性的逐个剔除分析的敏感性分析证实了这些关系的稳健性。本研究探讨了睡眠与微生物分类群和途径之间的潜在因果关系，为它们之间的复杂相互作用提供了新的见解。
