基于孟德尔随机化的肝功能和脂质代谢水平与睡眠障碍的因果关联分析

何威; 朱述可; 李春雨; 杜雪; 李佳芮

doi:10.12449/JCH241020

基于孟德尔随机化的肝功能和脂质代谢水平与睡眠障碍的因果关联分析

DOI: 10.12449/JCH241020

何威^1, , ,,
朱述可²,
李春雨²,
杜雪²,
李佳芮²

1.
长春市中医院脑病科，长春 130000
2.
长春中医药大学中医学院，长春 130000

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：何威负责拟定写作思路，指导撰写文章并最后定稿；朱述可负责课题设计，资料分析，撰写论文，修改论文；李春雨、杜雪、李佳芮参与检索文献，收集数据。

详细信息

通信作者:
何威， 297378127@qq.com （ORCID： 0009-0009-5281-734X）

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出版历程
- 收稿日期: 2024-01-27
- 录用日期: 2024-05-23
- 出版日期: 2024-10-25

Causal association of liver function and lipid metabolism levels with sleep disorders based on Mendelian randomization

Wei HE^{1
, ,
,},
Shuke ZHU²,
Chunyu LI²,
Xue DU²,
Jiarui LI²

1.
Department of Encephalopathy，Changchun Hospital of Traditional Chinese Medicine，Changchun 130000，China
2.
College of Traditional Chinese Medicine，Changchun University of Chinese Medicine，Changchun 130000，China

More Information

Corresponding author: HE Wei， 297378127@qq.com （ORCID： 0009-0009-5281-734X）

摘要

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。
- 肝功能 /
- 脂质代谢 /
- 睡眠障碍 /
- 孟德尔随机化分析
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.
- Liver Function /
- Lipid Metabolism /
- Sleep Disorders /
- Mendelian Randomization Analysis

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注： a，ALT散点图；b，AST散点图；c，GGT散点图；d，Alb散点图；e，TP散点图；f，TBil散点图；g，ALP散点图。

图 1 肝功能指标孟德尔随机化结果散点图

Figure 1. Mendelian randomization result scatter plot of liver function indicators

下载: 全尺寸图片幻灯片

注： a，TG散点图；b，TG/G3P散点图；c，TC散点图；d，HDL-C散点图；e，LDL-C：低密散点图；f，PUFA散点图；g，TFA散点图；h，PUFA/TFA散点图。

图 2 脂质代谢指标孟德尔随机化结果散点图

Figure 2. Mendelian randomization result scatter plot of lipid metabolism indicators

下载: 全尺寸图片幻灯片

表 1 样本数据基本信息

Table 1. Basic information of sample data

数据名称	年份	人群	SNP数量	GWASID
ALT	2021	欧洲人	4 231 965	ebi-a-GCST90025979
AST	2021	欧洲人	4 231 525	ebi-a-GCST90025980
GGT	2018	欧洲人	13 586 026	ukb-d-30730_raw
Alb	2022	欧洲人	11 590 399	ebi-a-GCST90092807
TP	2021	欧洲人	4 218 824	ebi-a-GCST90025995
TBil	2018	欧洲人	13 585 986	ukb-d-30840_irnt
ALP	2018	欧洲人	13 586 006	ukb-d-30610_raw
TG	2018	欧洲人	13 586 007	ukb-d-30870_raw
TG/G3P	2022	欧洲人	11 590 399	ebi-a-GCST90092983
TC	2022	欧洲人	13 586 006	ebi-a-GCST90092985
HDL-C	2021	欧洲人	4 218 934	ebi-a-GCST90025956
LDL-C	2021	欧洲人	19 037 976	ebi-a-GCST90018961
PUFA	2022	欧洲人	11 590 399	ebi-a-GCST90092939
TFA	2016	欧洲人	11 412 092	met-c-936
PUFA/TFA	2022	欧洲人	11 590 399	ebi-a-GCST90092941
睡眠障碍	2021	欧洲人	16 380 466	Finn-KRA_PSY_SLEEP_NONORG

下载: 导出CSV

表 2 孟德尔随机化结果

Table 2. Mendelian Randomization Results

暴露因素	分析方法	B值	P值	OR	95%CI	P_多效性	P_异质性
ALT	IVW	-0.084	0.388	0.919	0.759～1.113	0.781	0.255
AST	IVW	-0.026	0.774	0.974	0.817～1.162	0.926	0.640
GGT	IVW	0.003	0.300	1.003	0.997～1.008	0.614	0.976
Alb	IVW	-0.318	0.042	0.728	0.535～0.989	0.721	0.986
TP	IVW	-0.043	0.646	0.957	0.795～1.153	0.410	0.551
TBil	IVW	0.051	0.181	1.052	0.998～1.134	0.085	0.859
ALP	IVW	<-0.001	0.864	1.005	0.996～1.005	0.598	0.407
TG	IVW	<0.001	0.864	1.000	0.996～1.005	0.598	0.407
TG/G3P	IVW	0.201	0.013	1.222	1.044～1.431	0.257	0.865
TC	IVW	-0.003	0.976	0.997	0.801～1.241	0.784	0.117
HDL-C	IVW	-0.129	0.027	0.879	0.784～0.986	0.696	0.221
LDL-C	IVW	-0.034	0.656	0.966	0.831～1.124	0.207	0.446
PUFA	IVW	0.062	0.502	0.940	0.784～1.123	0.901	0.277
TFA	IVW	0.071	0.480	1.073	0.882～1.307	0.348	0.402
PIFA/TFA	IVW	-0.223	0.047	0.800	0.642～0.998	0.087	0.757

下载: 导出CSV

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