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Determination of shared genetic etiology and possible causal relations between tobacco smoking and depression

Published online by Cambridge University Press:  06 April 2020

Yinghao Yao ,
Yi Xu ,
Zhen Cai ,
Qiang Liu ,
Yunlong Ma ,
Andria N. Li ,
Thomas J. Payne  and
Ming D. Li Open the ORCID record for Ming D. Li [Opens in a new window]
Yinghao Yao
Affiliation:
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
Yi Xu
Affiliation:
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
Zhen Cai
Affiliation:
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
Qiang Liu
Affiliation:
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
Yunlong Ma
Affiliation:
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
Andria N. Li
Affiliation:
College of Arts and Sciences, University of Virginia, VA, USA
Thomas J. Payne
Affiliation:
Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS, USA
Ming D. Li*
Affiliation:
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 Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China
*
Author for correspondence: Ming D. Li, E-mail: ml2km@zju.edu.cn or limd586@outlook.com
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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.

Keywords

Depressiongenesmolecular mechanismssmoking
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 11 , August 2021 , pp. 1870 - 1879
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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