Yao Yinghao, Xu Yi, Cai Zhen, Liu Qiang, Ma Yunlong, Li Andria N, Payne Thomas J, Li Ming D
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
College of Arts and Sciences, University of Virginia, VA, USA.
Psychol Med. 2021 Aug;51(11):1870-1879. doi: 10.1017/S003329172000063X. Epub 2020 Apr 6.
Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.
In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).
By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10-25) and a negative correlation between MDD and former smoking (rg = -0.298; p = 1.59 × 10-24). MR analysis suggested that genetic liability for depression increased smoking.
These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.
吸烟与重度抑郁症（MDD）密切相关。然而，这种共病的任何遗传病因及因果关系却知之甚少，尤其是在全基因组水平上。
在本次计算机模拟研究中，我们通过使用包括贝叶斯共定位分析、连锁不平衡评分回归、变异效应大小相关分析和孟德尔随机化（MR）在内的各种生物统计学方法，分析了精神疾病遗传联盟针对MDD的全基因组关联研究（n = 191005）以及英国生物银行针对吸烟情况（n = 337030）的汇总数据。
通过采用基因优先排序方法，我们确定了MDD和吸烟共有的43个基因，这些基因在膜电位、γ-氨基丁酸受体活性和逆行性内源性大麻素信号通路中显著富集，表明共病机制涉及神经递质系统。根据连锁不平衡评分回归，我们发现MDD与当前吸烟之间存在强正相关（rg = 0.365；p = 7.23×10-25），而MDD与既往吸烟之间存在负相关（rg = -0.298；p = 1.59×10-24）。MR分析表明，抑郁症的遗传易感性会增加吸烟行为。
这些发现揭示了MDD和吸烟的伴随情况，并支持使用吸烟进行自我治疗以对抗抑郁症。
