Glycoprotein acetyls and depression: Testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses.
Glycoprotein acetyls and depression: Testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses.
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DOI：
10.1016/j.jad.2023.05.033
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发表时间：
2023-08-15
影响因子：
6.6
通讯作者：
Fraser A
中科院分区：
文献类型：
--
作者：
Crick DCP;Sanderson E;Jones H;Goulding N;Borges MC;Clayton G;Carter AR;Halligan S;Lawlor DA;Khandaker GM;Fraser A
炎症与抑郁症有关，但因果关系尚不清楚。我们研究了炎症和抑郁症之间的潜在因果关系和作用方向。使用来自ALSPAC出生队列（n=4021; 42.18%男性）的数据，我们使用多变量回归来研究GlycA与抑郁症和抑郁症状的双向纵向关联，在18岁和24岁时进行评估。我们使用双样本孟德尔随机化（MR）来研究潜在的因果关系和方向性。GlycA的遗传变异来自英国生物库（UKB）（N= 115，078）;抑郁症的遗传变异来自精神病基因组学联盟和UKB（N= 500，199）;抑郁症状的遗传变异来自社会科学遗传协会联盟（N= 161，460）。除了逆方差加权法外，我们还使用敏感性分析来加强因果推断。我们进行了多变量MR调整身体质量指数（BMI），由于已知的遗传相关性炎症，抑郁症和BMI。在队列分析中，调整潜在混杂因素后，我们没有发现GlycA和抑郁症状评分之间存在关联的证据，反之亦然。我们观察到GlycA与抑郁症之间的关联（OR= 1.18，95%CI：1.03 - 1.36）。MR表明GlycA对抑郁症没有因果关系，但抑郁症对GlycA有因果关系（GlycA的平均差异= 0.09; 95%CI：0.03 - 0.16），这在一些（但不是所有）敏感性分析中得以维持。GWAS样本重叠可能导致偏倚。我们没有发现GlycA对抑郁症有影响的一致证据。有证据表明，抑郁症增加了MR分析中的GlycA，但这可能受到BMI的混淆/介导。
Inflammation is associated with depression, but causality remains unclear. We investigated potential causality and direction of effect between inflammation and depression. Using data from the ALSPAC birth cohort (n=4021; 42.18% male), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression and depression symptoms, assessed at ages 18y and 24y. We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKB) (N=115,078); for depression from the Psychiatric Genomics Consortium and UKB (N=500,199); and for depressive symptoms (N=161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI. In the cohort analysis, after adjusting for potential confounders we found no evidence of associations between GlycA and depression symptoms score or vice versa. We observed an association between GlycA and depression (OR=1·18, 95% CI: 1·03-1·36). MR suggested no causal effect of GlycA on depression, but there was a causal effect of depression on GlycA (mean difference in GlycA = 0·09; 95% CI: 0·03-0·16), which was maintained in some, but not all, sensitivity analyses. The GWAS sample overlap could incur bias. We found no consistent evidence for an effect of GlycA on depression. There was evidence that depression increases GlycA in the MR analysis, but this may be confounded/mediated by BMI.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
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作者：
Capuron, L;Ravaud, A;Dantzer, R
通讯作者：
Dantzer, R
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Hannestad, Jonas;DellaGioia, Nicole;Bloch, Michael
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作者：
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