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Genetically predicted metabolites mediate the causal associations between autoimmune thyroiditis and immune cells

Authors :
Yongzhao Chen
Bo Jiang
Cheng Qu
Chaoyu Jiang
Chen Zhang
Yanxue Wang
Fei Chen
Xitai Sun
Lei Su
Yuqian Luo
Source :
Frontiers in Endocrinology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

IntroductionWe aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between.MethodsUsing summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites.ResultsWe identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%.DiscussionOur study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

Details

Language :
English
ISSN :
16642392
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Endocrinology
Publication Type :
Academic Journal
Accession number :
edsdoj.b141c200cc684ec0a08a924beb9dfcb5
Document Type :
article
Full Text :
https://doi.org/10.3389/fendo.2024.1424957