Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, Australia.
Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Depress Anxiety. 2019 Dec;36(12):1154-1162. doi: 10.1002/da.22963. Epub 2019 Oct 14.
This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among individuals with or without depression.
We used data on 251,125 individuals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)-related genetic risk score (GRS ) as an instrument for depression. We also examined whether depression modifies genetic susceptibility to high BMI, by investigating the interaction between depression and the BMI-related GRS .
We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04-0.13). Further, the contribution of genetic risk to high BMI was higher among individuals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD; 95%CI 0.23-0.25) higher BMI among depressed individuals compared to 0.20 SD (95%CI 0.19-0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an individual of average height. Amongst the individual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic-pituitary adrenal axis (p = 5.7 × 10 ).
Genetic predisposition to high BMI was higher among depressed than to nondepressed individuals. This study provides support for a possible role of MC4R in the link between depression and obesity.
本研究旨在探讨抑郁与体重指数（BMI）之间的关联，并研究抑郁患者与非抑郁患者之间，BMI 升高的遗传易感性是否存在差异。
我们使用了英国生物库中 251125 名白种英国人的数据。我们使用与重度抑郁症（MDD）相关的遗传风险评分（GRS）作为抑郁的工具，进行孟德尔随机化（MR）分析，以检验抑郁与 BMI 之间的因果关系。我们还通过研究抑郁与 BMI 相关 GRS 之间的相互作用，来检验抑郁是否改变了 BMI 升高的遗传易感性。
我们发现了观察性和遗传证据表明抑郁与 BMI 之间存在关联（MR 贝塔：0.09，95%置信区间[CI]：0.04-0.13）。此外，与对照组相比，抑郁患者的遗传风险对 BMI 升高的贡献更高。与非抑郁个体相比，抑郁个体携带 10 个额外的 BMI 升高等位基因与 0.24 个标准差（SD；95%CI：0.23-0.25）更高的 BMI 相关，而对照组的 0.20 SD（95%CI：0.19-0.21），这相当于平均身高的个体体重增加 3.4 公斤和 2.8 公斤。在个体基因座中，最显著的相互作用证据是 MC4R 附近的一个变体，该基因已知同时影响食欲调节和下丘脑-垂体-肾上腺轴（p=5.7×10）。
与非抑郁个体相比，BMI 升高的遗传易感性在抑郁个体中更高。本研究为 MC4R 在抑郁与肥胖之间的联系中可能发挥的作用提供了支持。
