Association between insomnia and type 2 diabetes:A two-sample Mendelian rando-mization study
10.19723/j.issn.1671-167X.2024.01.027
- VernacularTitle:基于两样本孟德尔随机化的失眠与2型糖尿病关联研究
- Author:
Yujia MA
1
;
Ranli LU
;
Zechen ZHOU
;
Xiaoyi LI
;
Zeyu YAN
;
Yiqun WU
;
Dafang CHEN
Author Information
1. 北京大学公共卫生学院流行病与卫生统计学系,北京大学重大疾病流行病学教育部重点实验室,北京 100191
- Keywords:
Sleep initiation and maintenance disorders;
Diabetes mellitus,type 2;
Mendelian rando-mization analysis
- From:
Journal of Peking University(Health Sciences)
2024;56(1):174-178
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.Methods:We identified strong,independent single nucleotide polymorphisms(SNPs)of insomnia from the most up to date genome wide association studies(GWAS)within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus.After excluding SNPs that were significantly associated with smoking,physical activity,alcohol consumption,educational attainment,obesity,or type 2 diabetes mellitus,we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting(IVW)method.Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association.We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables.We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from ze-ro.In addition,the leave-one-out method was used for sensitivity analysis to verify the stability and relia-bility of the results.Results:We selected 248 SNPs independently associated with insomnia at the genome-wide level(P＜5 ×10-8)as a preliminary candidate set of instrumental variables.After clum-ping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs,a total of 167 SNPs associated with insomnia were included as final instrumental variables.The F statistic of this study was 39.74,which was in line with the relevance assumption of Mendelian randomi-zation.IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1.14 times more likely to develop type 2 diabetes mellitus than those without insomnia(95％CI:1.09-1.21,P＜0.001).The weighted median estimator(WME)method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus.And MR-Egger re-gression also showed that the effect was less likely to be triggered by pleiotropy.Sensitivity analyses pro-duced directionally similar estimates.Conclusion:Insomnia is a risk factor of type 2 diabetes mellitus,which has positively effects on type 2 diabetes mellitus.Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.
