Body mass index, smoking behavior, and depression mediated the effects of schizophrenia on chronic obstructive pulmonary disease: trans-ethnic Mendelian-randomization analysis

作者全名：Ni, Yao; Zhang, DaWei; Tang, Wenlong; Xiang, Liming; Cheng, Xiaoding; Zhang, Youqian; Feng, Yanyan

作者地址：[Ni, Yao; Tang, Wenlong; Xiang, Liming; Cheng, Xiaoding; Feng, Yanyan] Chengdu Second Peoples Hosp, Dept Dermatovenereol, Chengdu, Sichuan, Peoples R China; [Zhang, DaWei] Chengdu Second Peoples Hosp, Dept Clin Lab, Chengdu, Sichuan, Peoples R China; [Zhang, DaWei] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Lab, Chongqing, Peoples R China; [Zhang, Youqian] Yangtze Univ, Hlth Sci Ctr, Jingzhou, Hubei, Peoples R China

通信作者：Feng, YY (通讯作者)，Chengdu Second Peoples Hosp, Dept Dermatovenereol, Chengdu, Sichuan, Peoples R China.; Zhang, YQ (通讯作者)，Yangtze Univ, Hlth Sci Ctr, Jingzhou, Hubei, Peoples R China.

来源：FRONTIERS IN PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001239310100001

JCR分区：Q2

影响因子：3.2

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Mendelian randomization; chronic obstructive pulmonary disease; schizophrenia; mediation analysis; causality

摘要：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<5x10-(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 (r(g) = 0.141, P = 6.16x10-(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, P-FDR= 0.015). Additionally, replication datasets provide evidence of consistent causal associations(P < 0.05 & P-FDR < 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 = 6.98x10-(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, P-FDR= 0.761) ancestry. No causal associations were found in the reverse analysis across the four ancestries (P > 0.05 & P-FDR > 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.

基金机构：Science and Technology Department of Sichuan Province10.13039/501100004829

基金资助正文：All data used in this article are from publicly available GWAS studies, and the data are available from the original article.