睡眠性状与肠易激综合征的孟德尔随机化研究

目的 采用孟德尔随机化(MR)方法探索睡眠性状与肠易激综合征(IBS)的因果关系。 方法 利用大规模全基因组关联研究汇总数据和芬兰生物银行数据(FinnGen),选择相互独立且与睡眠性状密切相关的遗传位点作为工具变量,通过逆方差加权法(MR-IVW)、加权中位数法、简单中位数法、稳健的调整轮廓评分法、MR多效性残差和与异质性法(MR-PRESSO)等MR方法,以比值比(OR值)作为评价指标对睡眠性状与IBS的因果关系进行探讨。 结果 MR-IVW结果显示,过短睡眠和失眠分别导致IBS发病风险增高147%(OR=2.47, 95%CI: 1.13~5.41 )和18%(OR=1.18, 95%CI: 1.14~1.22 ),早起型睡眠习惯会导致IBS发病风险降低12%(OR=0.88, 95%CI: 0.84~0.92 )。外部数据验证结果显示,仅失眠与IBS发病风险的关联有统计学意义(P<0.001)。多变量MR方法校正相关协变量后,失眠与IBS的关联效应仍有统计学意义(P<0.001)。 结论 过短睡眠和失眠会增加IBS的发病风险。

Mendelian randomization study of sleep phenotypes and irritable bowel syndrome

Objective To explore the causal relationship between sleep phenotypes and irritable bowel syndrome(IBS). Methods Mutually independent genetic variants closely related to sleep phenotypes were chosen as instrumental variables from the genome-wide association study database(GWAS)and the Finnish Biobank database(FinnGen). With odds ratio(OR)as an outcome indicator, the causal relationship between sleep phenotypes and IBS was analyzed using MR methods, including inverse-variance weighted(MR-IVW), weighted median, simple median method, robust adjusted contour score method, pleiotropic residual sum, and heterogeneity. Results MR-IVW results showed that short sleep duration and insomnia led to an increased risk of IBS by 147%(OR=2.47, 95%CI: 1.13-5.41)and 18% (OR=1.18, 95%CI: 1.14-1.22), respectively. Morning habits were associated with a 12% lower risk of IBS(OR=0.88, 95%CI: 0.84-0.92). The results of external data validation showed that only insomnia was associated with a statistically significant risk of IBS(P<0.001). After relevant covariates were adjusted with multivariate MR methods, the association effect between insomnia and IBS remained statistically significant(P<0.001). Conclusion Short sleep duration and insomnia will increase the risk of IBS.