摘要
目的 采用孟德尔随机化分析肝功能和脂质代谢水平与睡眠障碍的因果关联.方法 对GWAS进行分析,暴露因素为肝功能和脂质代谢水平[ALT、AST、GGT、Alb、血清总蛋白(TP)、TBil、ALP、TG、TG与磷酸甘油酯的比例(TG/G3P)、TC、HDL-C、LDL-C、多不饱和脂肪酸(PUFA)、总脂肪酸(TFA)、PUFA/TFA],结局因素为睡眠障碍(非器质性).采用逆方差加权法(IVW)、MR-Egger法、Simple Mode法、加权中位数法和Weighted Mode法等回归模型进行孟德尔随机化分析.结果 血清Alb(OR=0.728,95%CI:0.535～0.989,P＜0.05),HDL-C(OR=0.879,95%CI:0.784～0.986,P＜0.05)和PUFA/TFA(OR=0.800,95%CI:0.642～0.998,P＜0.05)与睡眠障碍呈负相关.TG/G3P(OR=1.222,95%CI:1.044～1.431,P＜0.05)与睡眠障碍呈正相关.孟德尔随机化结果未显示ALT、AST、GGT、TP、TBil、ALP、TG、TC、LDL-C、PUFA、TFA与睡眠障碍有因果关系(P值均＞0.05).ME-Egger截距测试结果表明分析结果不存在多效性(P＞0.05),孟德尔随机化在本研究中为因果推断的有效方法.结论 根据孟德尔随机化分析结果,肝功能和脂质代谢水平与睡眠障碍之间存在显著关联.在预测睡眠障碍的发生风险以及干预方面,可以考虑利用肝功能和脂质代谢水平作为睡眠障碍发生风险以及干预的指标.
Abstract
Objective To investigate the causal association of liver function and lipid metabolism levels with sleep disorders based on the Mendelian randomization analysis.Methods The analysis was conducted using the data from genome-wide association studies,with the exposure factors of liver function and lipid metabolism levels(alanine aminotransferase[ALT],aspartate aminotransferase[AST],gamma-glutamyl transpeptidase[GGT],albumin[Alb],serum total protein[TP],total bilirubin[TBil],alkaline phosphatase[ALP],triglyceride[TG],triglyceride-to-glycerol-3-phosphate[TG/G3P]ratio,total cholesterol[TC],high-density lipoprotein cholesterol[HDL-C],low-density lipoprotein cholesterol[LDL-C],poly-unsaturated fatty acids[PUFA],total fatty acids[TFA],PUFA/TFA ratio)and the outcome factor of sleep disorders(nonorganic).The regression models including inverse variance weighted,MR-Egger,Simple mode,weighted median,and Weighted mode were used to perform the Mendelian randomization analysis.Results Serum Alb(odds ratio[OR]=0.728,95%confidence interval[CI]:0.535-0.989,P＜0.05),HDL-C(OR=0.879,95%CI:0.784-0.986,P＜0.05),and PUFA/TFA ratio(OR=0.800,95%CI:0.642-0.998,P＜0.05)were negatively associated with sleep disorders,while TG/G3P ratio(OR=1.222,95%CI:1.044-1.431,P＜0.05)was positively associated with sleep disorders.The results of Mendelian randomization did not show a causal association of ALT,AST,GGT,TP,TBil,ALP,TG,TC,LDL-C,PUFA,and TFA with sleep disorders(all P＞0.05).The results of the MR-Egger intercept test showed no pleiotropy(P＞0.05),and Mendelian randomization was a valid method for causal inference in this study.Conclusion According to the results of the Mendelian randomization analysis,liver function and lipid metabolism show significant association with sleep disorders.Liver function and lipid metabolism can be used as indicators for predicting the risk of sleep disorders and performing intervention.
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