孟德尔随机化研究未提供证据表明抑郁和多发性硬化症之间双向关系存在因果关系。

Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.

机构信息

Department of Neurology, University of California San Francisco, San Francisco, CA, USA/Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada/Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

出版信息

Mult Scler. 2021 Nov;27(13):2077-2084. doi: 10.1177/1352458521993075. Epub 2021 Feb 16.

DOI:10.1177/1352458521993075

PMID:33591230

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8364919/

Abstract

BACKGROUND

Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear.

OBJECTIVE

The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR).

METHODS

We selected genetic instruments associated with risk of MDD ( = 660,937 cases; 1,453,489 controls) and MS ( = 47,429 cases; 68,374 controls). Using two-sample MR, we examined putative causal effects in either direction, with sensitivity analyses to assess pleiotropy. Also, we adjusted for body mass index (BMI) in multivariable MR.

RESULTS

We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90-1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99-1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09-1.65) and MDD (OR = 1.08, 95% CI = 1.01-1.15).

CONCLUSION

This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.

摘要

背景

多发性硬化症（MS）中常见重度抑郁症（MDD），且其发病率在 MS 确诊前上升。然而，这种关联的因果关系和方向尚不清楚。

目的

本研究旨在使用孟德尔随机化（MR）研究 MS 和 MDD 之间的双向关系。

方法

我们选择了与 MDD 风险相关的遗传工具（ = 660937 例；1453489 例对照）和 MS 风险相关的遗传工具（ = 47429 例；68374 例对照）。使用两样本 MR，我们检查了两个方向的可能因果效应，并进行敏感性分析以评估多效性。此外，我们还在多变量 MR 中调整了体重指数（BMI）。

结果

我们没有发现 MDD 遗传易感性对 MS 发病几率的影响（OR=1.07/几率翻倍，95%CI=0.90-1.28）。同样，我们的研究结果也不支持 MS 遗传易感性对 MDD 的因果效应（OR=1.00/几率翻倍，95%CI=0.99-1.01）。尽管存在异质性，但敏感性分析表明多效性引起的偏倚不太可能。相反，朝向更高 BMI 的遗传倾向会增加 MS 的发病几率（OR=1.34/SD 增加，95%CI=1.09-1.65）和 MDD 的发病几率（OR=1.08，95%CI=1.01-1.15）。