两样本孟德尔随机化法分析抑郁症与间质性肺病关系的研究

doi:10.3969/j.issn.1006-5253.2023.02.001

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摘要目的采用孟德尔随机化方法分析抑郁症与间质性肺病（ILD）之间的因果关系，为ILD的预防、治疗及预后评估提供新的思路。方法利用大样本全基因关联研究汇总数据，选择与抑郁症密切相关的遗传位点作为工具变量，逆方差加权法为主，加权中位数法和MR-Egger 回归为辅对数据进行两样本孟德尔随机化分析。以OR值评价抑郁症与ILD之间的因果关系，异质性检验、基因多效性检验和敏感性分析3种方法评估结果的稳定性和可靠性。结果共纳入37个单核苷酸多态性（SNP）位点作为工具变量，逆方差加权法估计抑郁症患者患ILD的风险（OR）是健康人群的1.21倍（95%CI：1.075~1.361，P=0.002）。加权中位数法同样支持抑郁症和ILD之间存在因果效应（95%CI：1.118~1.564，P=0.001）。逆方差加权法和MR-Egger回归的异质性检验结果表明不存在异质性，MR-Egger回归截距项和MR-PRESSO方法检验表明结果受基因多效性影响的可能性较小，leave-one-out分析未发现非特异性SNP。结论抑郁症与ILD之间可能存在正向因果关联。

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	陈铭
	刘金婵
	唐田书
	许德华
	陈晓琳
	饶绍奇

关键词 ：抑郁症, 间质性肺病, 孟德尔随机化

Abstract：Objective To reveal the causal relationship between depression and interstitial lung disease (ILD) by using Mendelian randomization method, and to provide new ideas for the prevention, treatment and prognosis of ILD.Methods The genetic loci closely associated with depression were selected as instrumental variables using pooled data from the Genome-Wide Association Study (GWAS). The inverse variance weighting method was used as the primary analysis method, and the weighted median method and MR-Egger regression were used as auxiliary methods to perform two-sample Mendelian randomization analysis; OR values were used to evaluate the causal relationship between depression and ILD, and heterogeneity tests, gene multiplicity tests and sensitivity analyses were performed to assess the stability and reliability of the results.Results Thirty-seven single nucleotide polymorphism (SNP) loci were included as instrumental variables. MR-Egger regression estimated that the risk of lung cancer in patients with depression was 1.21 times that of healthy people (95%CI: 1.075-1.361, P=0.002). The weighted median method also supported a causal effect between depression and interstitial lung disease (95% CI: 1.118-1.564, P=0.001). The heterogeneity test results of the inverse variance-weighted method and MR-Egger regression showed that there was no heterogeneity; MR-Egger regression intercept term and MR-PRESSO method tests showed that the results were less likely to be affected by gene pleiotropism; no non-specific SNPs were found in leave-one-out analysis.Conclusion There may be a positive causal association between depression and ILD.

Key words： depression interstitial lung disease Mendelian randomization

收稿日期: 2022-12-30

PACS:

基金资助:国家自然科学基金（81373085）

通讯作者: 饶绍奇，Email：raoshaoq@gdmu.edu.cn

引用本文:

陈铭，刘金婵，唐田书，许德华，陈晓琳，饶绍奇. 两样本孟德尔随机化法分析抑郁症与间质性肺病关系的研究[J]. 中国医院统计, 2023, 30(2): 81-86.
Chen Ming，Liu Jinchan，Tang Tianshu，Xu Dehua，Chen Xiaolin，Rao Shaoqi. Causal relationship between depression and interstitial lung disease with two-sample Mendelian randomization. journal1, 2023, 30(2): 81-86.

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