Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.
Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.
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DOI：
10.1177/1352458521993075
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Kowalec K
中科院分区：
文献类型：
--
作者：
Harroud A;Marrie RA;Fitzgerald KC;Salter A;Lu Y;Patel M;Kowalec K
重度抑郁障碍（MDD）常见于多发性硬化症（MS），其发病率在MS诊断前上升。然而，这种联系的因果关系和方向仍不清楚。采用孟德尔随机化方法研究多发性硬化症与重度抑郁症的双向关系。我们选择了与MDD （n=660,937例，1,453,489例对照）和MS （n=47,429例，68,374例对照）风险相关的遗传工具。使用双样本MR，我们检查了两个方向的假定因果效应，并通过敏感性分析来评估多效性。此外，我们在多变量mr中调整了体重指数（BMI）。我们发现MDD的遗传易感性对MS的几率没有影响（OR=1.07/几率加倍，95%CI 0.90-1.28）。同样，我们的研究结果不支持MS遗传倾向对MDD的因果影响（OR=1.00/几率加倍，95%CI 0.99-1.01）。尽管存在异质性，但敏感性分析表明，多效性不太可能产生偏倚。相反，高BMI的遗传易感性增加了MS （OR=1.34/SD增加，95%CI 1.09-1.65）和MDD （OR=1.08, 95%CI 1.01-1.15）的几率。本研究不支持MDD遗传易感性和MS易感性之间的因果关系，反之亦然。遗传证据表明，肥胖与这两种疾病的共性可能部分解释了多发性硬化症诊断前抑郁症发病率增加的原因。
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. To investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR). We selected genetic instruments associated with risk of MDD (n=660,937 cases; 1,453,489 controls) and MS (n=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. 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 towards 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). This study does not support a causal association between MDD genetic liability and MS susceptiblity, and vice versa. Genetic evidence suggests commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
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影响因子：
3.7
作者：
Cree BA;Rioux JD;McCauley JL;Gourraud PA;Goyette P;McElroy J;De Jager P;Santaniello A;Vyse TJ;Gregersen PK;Mirel D;Hafler DA;Haines JL;Pericak-Vance MA;Compston A;Sawcer SJ;Oksenberg JR;Hauser SL;IMAGEN;IMSGC
通讯作者：
IMSGC
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2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
9.9
作者：
McKay, Kyla A.;Tremlett, Helen;Marrie, Ruth Ann
通讯作者：
Marrie, Ruth Ann
影响因子：
9.9
作者：
Harroud, Adil;Morris, John A.;Richards, J. Brent
通讯作者：
Richards, J. Brent
影响因子：
5.8
作者：
Harroud, Adil;Richards, J. Brent
通讯作者：
Richards, J. Brent