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职业暴露与类风湿关节炎和强直性脊柱炎发病因果关系的双样本孟德尔随机化研究。

Causality of occupational exposure on rheumatoid arthritis and ankylosing spondylitis: a two-sample mendelian randomization study.

机构信息

Graduate School, Beijing University of Chinese Medicine, Beijing, China.

Department of Computer Science and Technology, Changchun Normal University, Changchun, China.

出版信息

Front Immunol. 2023 Oct 2;14:1223810. doi: 10.3389/fimmu.2023.1223810. eCollection 2023.


DOI:10.3389/fimmu.2023.1223810
PMID:37849761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10577282/
Abstract

OBJECTIVE: This study aimed to explore the potential causal link between three specific types of occupational exposure on rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHOD: A Two-sample Mendelian randomization (TSMR) analysis, comprising univariate MR (UVMR) and multivariate MR (MVMR) analyses, was performed to investigate the potential causal association between three types of occupational exposures, jobs involving mainly walking or standing (JWS), jobs involving heavy manual or physical work (JMP), and jobs involving shift work(JSW) on RA and AS. Genetic variants for genome-wide association studies (GWAS) of occupational exposure and AS were obtained from the UK Biobank. GWAS summary data for RA were obtained from FinnGen Biobank analysis. For UVMR, six methods of Inverse Variance Weighted (IVW), MR-Egger, Weighted Mode, Weighted Median, Simple Mode, MR pleiotropy residual sum, and outlier (MR-PRESSO) were used for the analysis. The MVMR was analyzed using the IVW model as well as the MR-Egger model. RESULTS: The UVMR suggested no causal relationship between the three occupational exposure and RA [IVW: P=0.59,0.21,0.63] or AS [IVW: P=0.43,0.57,0.04], as did the bidirectional MR [IVW: P=0.73,0.70,0.16], [IVW: P=0.65,0.68,0.74]. Although unadjusted MVMR suggested a causal relationship between JMP and AS [IVW: OR = 1.01, 95% CI = 1.00- 1.02, p = 0.02], the adjusted MVMR denied this relationship and concluded that there was no causal relationship between the other occupational exposure and either RA or AS. CONCLUSION: Our MR analysis did not establish a direct causal relationship between certain occupational exposures and either RA or AS.

摘要

目的:本研究旨在探讨三种特定职业暴露类型与类风湿关节炎(RA)和强直性脊柱炎(AS)之间潜在的因果关系。

方法:采用两样本 Mendelian 随机化(TSMR)分析,包括单变量 Mendelian 随机化(UVMR)和多变量 Mendelian 随机化(MVMR)分析,以研究三种职业暴露类型(主要行走或站立工作(JWS)、重体力或体力工作(JMP)和轮班工作(JSW))与 RA 和 AS 之间潜在的因果关联。用于 AS 的职业暴露和 AS 的全基因组关联研究(GWAS)的遗传变异从英国生物银行获得。RA 的 GWAS 汇总数据从芬兰基因生物银行分析中获得。对于 UVMR,使用六种Inverse Variance Weighted(IVW)方法、MR-Egger、Weighted Mode、Weighted Median、Simple Mode、MR pleiotropy residual sum 和 outlier(MR-PRESSO)进行分析。MVMR 分析采用 IVW 模型和 MR-Egger 模型。

结果:UVMR 表明三种职业暴露与 RA [IVW:P=0.59,0.21,0.63]或 AS [IVW:P=0.43,0.57,0.04]之间没有因果关系,双向 Mendelian 随机化也是如此 [IVW:P=0.73,0.70,0.16],[IVW:P=0.65,0.68,0.74]。尽管未经调整的 MVMR 表明 JMP 与 AS 之间存在因果关系 [IVW:OR=1.01,95%CI=1.00-1.02,p=0.02],但调整后的 MVMR 否认了这种关系,并得出结论,其他职业暴露与 RA 或 AS 之间没有因果关系。

结论:我们的 MR 分析并未确定某些职业暴露与 RA 或 AS 之间存在直接因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a681/10577282/ccc8b2e3e7db/fimmu-14-1223810-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a681/10577282/5dc9cae41ffb/fimmu-14-1223810-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a681/10577282/ccc8b2e3e7db/fimmu-14-1223810-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a681/10577282/5dc9cae41ffb/fimmu-14-1223810-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a681/10577282/ccc8b2e3e7db/fimmu-14-1223810-g002.jpg

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[4]
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本文引用的文献

[1]
The Associations of Chronotype and Shift Work With Rheumatoid Arthritis.

J Biol Rhythms. 2023-10

[2]
Causal relationship between smoking status, smoking frequency and bladder cancer: a Mendelian randomization study.

Genes Genomics. 2023-2

[3]
Association between work physical activity, dietary factors, and risk of rheumatoid arthritis.

Semin Arthritis Rheum. 2022-12

[4]
Pulmonary embolism and 529 human blood metabolites: genetic correlation and two-sample Mendelian randomization study.

BMC Genom Data. 2022-8-29

[5]
Two-Sample Multivariable Mendelian Randomization Analysis Using R.

Curr Protoc. 2021-12

[6]
Physical work exposure matrix for use in the UK Biobank.

Occup Med (Lond). 2022-2-22

[7]
Genetically Determined Chronic Low-Grade Inflammation and Hundreds of Health Outcomes in the UK Biobank and the FinnGen Population: A Phenome-Wide Mendelian Randomization Study.

Front Immunol. 2021

[8]
Low-grade systemic inflammation and the workplace.

Work. 2021

[9]
Association between Working Hours and Self-Rated Health.

Int J Environ Res Public Health. 2020-4-15

[10]
Obesity and its role in the management of rheumatoid and psoriatic arthritis.

Clin Rheumatol. 2020-4

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