Abstract:
BACKGROUNDS: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. METHODS: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). RESULTS: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. CONCLUSIONS:These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.
journal_name
Psychol Medjournal_title
Psychological medicineauthors
Yao Y,Xu Y,Cai Z,Liu Q,Ma Y,Li AN,Payne TJ,Li MDdoi
10.1017/S003329172000063Xsubject
Has Abstractpub_date
2020-04-06 00:00:00pages
1-10eissn
0033-2917issn
1469-8978pii
S003329172000063Xpub_type
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