2型糖尿病与抑郁症双向关系的研究孟德尔随机化研究

IF 10.1 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Renu Bala, Dale Handley, Alexandra Gillett, Harry Green, Jack Bowden, Andrew Wood, Inês Barroso, Cathryn M. Lewis, Jessica Tyrrell
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引用次数: 0

摘要

重度抑郁症(MDD)和2型糖尿病(T2D)是两种高度共发的全球健康挑战。在这里,我们的目的是利用GWAS汇总统计和个体水平(UK Biobank (UKB))数据中的孟德尔随机化(MR)来研究不同祖先中MDD和T2D之间的因果关系。我们评估了非糖尿病个体中MDD和T2D之间的双向因果关系(a) MDD和(b) MDD和血糖生物标志物(如TG:HDL-C比值,衡量胰岛素抵抗和空腹血糖)。在UKB中,我们还测试了T2D在治疗难治性抑郁症(TRD)中的作用。我们使用多变量磁共振(MVMR)来评估体重指数(BMI)在MDD与T2D关系中的作用。我们的研究结果表明,MDD遗传易感性增加一倍与T2D几率增加1.14相关(95% CI:1.09, 1.19),而T2D遗传易感性增加一倍与MDD几率增加1.02相关(95% CI:1.01, 1.03)。当按性别分层时,在UKB中观察到一致的效应估计,并提示T2D在TRD中的作用。GWAS衍生的T2D遗传变异簇强调了MDD关系中特定途径的重要性,包括通过体脂提高T2D风险的变异(OR:1.04;95% CI:1.02, 1.06),肥胖介导的胰岛素抵抗(OR:1.06;95% CI:1.04, 1.09)和残余血糖(OR: 1.02;95% CI:1.00, 1.04)。BMI的MVMR减弱了MDD和T2D之间的双向关系,特别是从MDD到T2D。在没有T2D的个体中,MDD的遗传易感性也与较高的TG:HDL-C比值相关(β:0.11;95% ci:0.08, 0.14)。我们提供了MDD和T2D之间双向因果关系的证据,MDD强烈预测胰岛素抵抗和T2D。T2D预测了MDD和TRD,并强调了肥胖和体脂途径在T2D与MDD关系中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Evidence of bidirectional relationship between type 2 diabetes and depression; a Mendelian randomization study

Evidence of bidirectional relationship between type 2 diabetes and depression; a Mendelian randomization study

Major depressive disorder (MDD) and type 2 diabetes (T2D) represent two global health challenges with a high degree of co-occurrence. Here, we aim to investigate the causal relationship between MDD and T2D in diverse ancestries using Mendelian randomization (MR) in GWAS summary statistic and individual level (UK Biobank (UKB)) data. We assessed the bi-directional causal relationship between: (a) MDD and T2D and (b) MDD and glycaemic biomarkers (e.g. TG:HDL-C ratio, a measure of insulin resistance, fasting glucose) in non-diabetic individuals. In UKB we also tested the role of T2D on treatment resistant depression (TRD). We used multivariable MR (MVMR) to assess the role of body mass index (BMI) in the MDD to T2D relationship. Our results demonstrated that a doubling in MDD genetic liability was associated with 1.14 higher odds of T2D (95% CI:1.09, 1.19), whilst a doubling in T2D genetic liability associated with 1.02 higher odds of MDD (95% CI:1.01, 1.03). Consistent effect estimates were observed in the UKB when stratifying by sex and suggested a role for T2D in TRD. T2D GWAS derived clusters of genetic variants highlighted the importance of specific pathways in the MDD relationship, including variants raising T2D risk via body fat (OR:1.04; 95% CI:1.02, 1.06), obesity mediated insulin resistance (OR:1.06; 95% CI:1.04, 1.09) and residual glycaemic (OR: 1.02; 95% CI:1.00, 1.04) pathways. MVMR with BMI attenuated the bidirectional relationship between MDD and T2D, particularly from MDD to T2D. Genetic liability to MDD was also associated with higher TG:HDL-C ratio in individuals without T2D (β:0.11; 95% CI:0.08, 0.14). We provide evidence of bidirectional causal association between MDD and T2D, with MDD strongly predicting insulin resistance and T2D. T2D predicted both MDD and TRD and highlighted the importance of obesity and body fat pathways in the T2D to MDD relationship.

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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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