摘要
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。
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,robust adjusted profile score,MR-pleiotropy residual sum and outlier(MR-PRESSO).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.
作者
张凯
司书成
李吉庆
刘晓雯
赵英琪
薛付忠
ZHANG Kai;SI Shucheng;LI Jiqing;LIU Xiaowen;ZHAO Yingqi;XUE Fuzhong(Department of Biostatistics,School of Public Health,Cheeloo College of Medicine,Shandong University,Jinan 250012,Shandong,China;Institute for Medical Dataology,Shandong University,Jinan 250002,Shandong,China)
出处
《山东大学学报（医学版）》
CAS
北大核心
2022年第8期109-114,共6页
Journal of Shandong University:Health Sciences
基金
国家重点研发计划(2020YFC2003500)
国家自然科学基金(81773547,82173625)
关键词
睡眠性状
失眠
肠易激综合征
孟德尔随机化
因果推断
Sleep phenotypes
Insomnia
Irritable bowel syndrome
Mendelian randomization
Causal inference
