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ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Schizophrenia
Volume 15 - 2024 |
doi: 10.3389/fpsyt.2024.1405107
This article is part of the Research Topic Underlying Neurobiological, Genetic, and Behavioral Mechanisms in Schizophrenia and Autism Spectrum Disorder View all 5 articles
Body Mass Index, Smoking Behavior, and Depression Mediated the Effects of Schizophrenia on Chronic Obstructive Pulmonary Disease: Trans-ethnic Mendelianrandomization Analysis
Provisionally accepted
Yao Ni
1
Da Wei Zhang
1
Wenlong Tang
1
Liming Xiang
1
Xiaoding Cheng
1
Youqian Zhang
2*
Yanyan Feng
1*- 1 Chengdu Second People's Hospital, Chengdu, Sichuan Province, China
- 2 Yangtze University, Jingzhou, China
Background: Previous studies have highlighted the association between schizophrenia (SCZ) and chronic obstructive pulmonary disease (COPD), yet the causal relationship remains unestablished. Methods: Under the genome-wide significance threshold (P<5×10-8), data from individuals of European (EUR) and East Asian (EAS) ancestries with SCZ were selected for analysis. Univariable Mendelian randomization (MR) explored the causal relationship between SCZ and COPD. Linkage disequilibrium score (LDSC) regression was used to calculate genetic correlation, while multivariable and mediation MR further investigated the roles of six confounding factors and their mediating effects. The primary method utilized was inverse-variance weighted (IVW), complemented by a series of sensitivity analyses and false discovery rate (FDR) correction. Results: LDSC analysis revealed a significant genetic correlation between SCZ and COPD within EUR ancestry (rg = 0.141, P = 6.16×10-7), with no such correlation found in EAS ancestry. IVW indicated a significant causal relationship between SCZ and COPD in EUR ancestry (OR = 1.042, 95% CI 1.013–1.071, P = 0.003, PFDR = 0.015). Additionally, replication datasets provide evidence of consistent causal associations(P < 0.05 & PFDR < 0.05). Multivariable and mediation MR analyses identified body mass index (BMI)(Mediation effect: 50.57%, P = 0.02), age of smoking initiation (Mediation effect: 27.42%, P = 0.02), and major depressive disorder (MDD) (Mediation effect: 60.45%, P = 6.98×10-5) as partial mediators of this causal relationship. No causal associations were observed in EAS (OR = 0.971, 95% CI 0.875–1.073, P = 0.571, PFDR = 0.761) ancestry. No causal associations were found in the reverse analysis across the four ancestries (P > 0.05 & PFDR > 0.05). Conclusions: This study confirmed a causal relationship between SCZ and the risk of COPD in EUR ancestry, with BMI, smoking, and MDD serving as key mediators. Future research on a larger scale is necessary to validate the generalizability of these findings across other ancestries.
Keywords: Mendelian randomization, chronic obstructive pulmonary disease, Schizophrenia, Mediation analysis, causality
Received: 22 Mar 2024; Accepted: 09 May 2024.
Copyright: © 2024 Ni, Zhang, Tang, Xiang, Cheng, Zhang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Youqian Zhang, Yangtze University, Jingzhou, China
Yanyan Feng, Chengdu Second People's Hospital, Chengdu, 610017, Sichuan Province, China
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