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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

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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
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。
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    通信作者:

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

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

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

     

  • 图  1  肝功能指标孟德尔随机化结果散点图

    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。

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

    图  2  脂质代谢指标孟德尔随机化结果散点图

    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。

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

    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 P 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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  • 收稿日期:  2024-01-27
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