Bao Wenzhao, Qi Li, Bao Yin, Wang Sai, Li Wei
Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, China.
Department of Otorhinolaryngology, The First Hospital of China Medical University, Shenyang, China.
Front Pharmacol. 2022 Aug 16;13:900788. doi: 10.3389/fphar.2022.900788. eCollection 2022.
Associations have been reported between sleep and irritable bowel syndrome (IBS). However, whether there exists a causation between them is still unknown. We employed the Mendelian randomization (MR) design to explore the causal relationship between sleep and IBS. All genetic associations with sleep-related traits reached genome-wide significance (-value < 5 × 10-8). The genetic associations with IBS were obtained from two independent large genome-wide association studies (GWAS), where non-FinnGen GWAS was in the discovery stage and FinnGen GWAS was in the validation stage. Primarily, the inverse-variance weighted method was employed to estimate the causal effects, and a meta-analysis was performed to combine the MR estimates. In the discovery, we observed that genetic liability to the "morning" chronotype could lower the risk of IBS [OR = 0.81 (0.76, 0.86)]. Also, the genetic liability to insomnia can increase the risk of IBS [OR = 2.86 (1.94, 4.23)] and such causation was supported by short sleep duration. In the validation stage, only insomnia displayed statistical significance [OR = 2.22 (1.09, 4.51)]. The meta-analysis suggested two genetically-determined sleep exposures can increase the risk of IBS, including insomnia [OR = 2.70 (1.92, 3.80)] and short sleep duration [OR = 2.46 (1.25, 4.86)]. Furthermore, the multivariable MR analysis suggested insomnia is an independent risk factor for IBS after adjusting for chronotype [OR = 2.32 (1.57, 3.43)] and short sleep duration [OR = 1.45 (1.13, 1.85)]. IBS cannot increase the risk of insomnia in the reverse MR analysis. Genetic susceptibility to insomnia can increase the risk of IBS, and improving sleep quality, especially targeting insomnia, can help to prevent IBS.
睡眠与肠易激综合征（IBS）之间的关联已有报道。然而，它们之间是否存在因果关系仍不清楚。我们采用孟德尔随机化（MR）设计来探讨睡眠与IBS之间的因果关系。所有与睡眠相关性状的基因关联均达到全基因组显著性（-值<5×10-8）。与IBS的基因关联来自两项独立的大型全基因组关联研究（GWAS），其中非芬兰基因组GWAS处于发现阶段，芬兰基因组GWAS处于验证阶段。首先，采用逆方差加权法估计因果效应，并进行荟萃分析以合并MR估计值。在发现阶段，我们观察到“早晨型”生物钟类型的遗传易感性可降低IBS风险[比值比=0.81（0.76，0.86）]。此外，失眠的遗传易感性可增加IBS风险[比值比=2.86（1.94，4.23）]，且这种因果关系得到短睡眠时间的支持。在验证阶段，只有失眠具有统计学意义[比值比=2.22（1.09，4.51）]。荟萃分析表明，两种由基因决定的睡眠暴露可增加IBS风险，包括失眠[比值比=2.70（1.92，3.80）]和短睡眠时间[比值比=2.46（1.25，4.86）]。此外，多变量MR分析表明，在调整生物钟类型[比值比=2.32（1.57，3.43）]和短睡眠时间[比值比=1.45（1.13，1.85）]后，失眠是IBS的独立危险因素。在反向MR分析中，IBS不会增加失眠风险。失眠的遗传易感性可增加IBS风险，改善睡眠质量，尤其是针对失眠，有助于预防IBS。
