Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption.
Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption.
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DOI：
10.1017/s0033291720002342
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发表时间：
2022-03
影响因子：
6.9
通讯作者：
Fabbri C
中科院分区：
文献类型：
--
作者：
Badini I;Coleman JRI;Hagenaars SP;Hotopf M;Breen G;Lewis CM;Fabbri C
抑郁症是一种非常普遍和异质性的疾病。本研究旨在确定具有非典型特征的抑郁症是否与其他抑郁症亚群相比在精神和免疫代谢特征上具有不同的遗传力和不同程度的多基因风险重叠。数据包括来自英国生物银行的30069名符合终身重度抑郁症标准的欧洲血统个体。报告体重增加和嗜睡的参与者被归类为↑WS抑郁症（N = 1854），其他参与者被归类为非↑WS抑郁症（N = 28215）。非↑WS抑郁患者进一步归类为↓WS抑郁（即体重减轻和失眠；N = 10 142）。使用全基因组汇总统计生成22个性状的多基因风险评分（PRS） （Bonferroni校正p = 2.1 × 10−4）。估计抑郁症亚组的单核苷酸多态性（SNP）遗传力。↑WS抑郁症与非↑WS抑郁症和↓WS抑郁症相比，BMI [OR = 1.20 (1.15-1.26), p = 2.37 × 10−14]和c -反应蛋白[OR = 1.11 (1.06-1.17), p = 8.86 × 10−06]的多基因风险更高。瘦素PRS接近显著性阈值（p = 2.99 × 10−04），但考虑体重指数调整后的瘦素GWAS汇总统计时，效果消失。每日饮酒的PRS与非↑WS抑郁症呈负相关[OR = 0.88 (0.83-0.93), p = 1.04 × 10 - 05]。↑WS抑郁症和↓WS抑郁症的snp遗传率差异不显著（分别为14.3%和12.2%）。WS抑郁症显示出免疫代谢特征和饮酒的明显遗传易感。这些遗传信号表明，包括免疫-心脏-代谢途径在内的生物学靶点可能与↑WS抑郁症患者的治疗有关。
Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups. Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10−4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated. ↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15–1.26), p = 2.37 × 10−14] and C-reactive protein [OR = 1.11 (1.06–1.17), p = 8.86 × 10−06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10−04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83–0.93), p = 1.04 × 10−05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively). ↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.