Genetically determined metabolites in Grave's disease: insight from a Mendelian randomization study
Yao Tan, Jiayang Yin, Jiamin Cao, Bingyu Xie, Feng Zhang, Wei Xiong- Endocrinology, Diabetes and Metabolism
Abstract
Context
Grave's disease (GD) is a prevalent autoimmune disorder with a complex etiology. The association between serum metabolites and GD remains partially understood.
Objective
This study aimed to elucidate the causal connections between serum metabolites and predisposition to GD, examining potential genetic interplay.
Methods
A two-sample Mendelian Randomization (MR) study was conducted on the GD analysis that included 2,836 cases and 374,441 controls. We utilized GWAS summary data from the FinnGen project, analyzing the causal impact of 486 serum metabolites on GD. Approaches used were the IVW methodology, Cochran's Q test, MR-Egger regression, MR-PRESSO, Steiger test, and LDSC analyses to assess genetic influence on metabolites and GD.
Results
Nineteen metabolites were identified as having a pronounced association with GD risk, of which 10 maintained noteworthy correlations post stringent sensitivity assessments. Three metabolites exhibited significant heritability: kynurenine (OR = 3.851, p = 6.09 × 10−4), a risk factor; glycerol 2-phosphate (OR = 0.549, p = 3.58 × 10−2) and 4-androsten-3beta,17beta-diol disulfate 2 (OR = 0.461, p = 1.34 × 10−2) were recognized as protective factors against GD. Crucially, all three exhibited no shared genetic interrelation with GD, further substantiating their potential causal significance in the disease.
Conclusion
This study unveils pivotal insights into the intricate relationships between serum metabolites and GD risk. By identifying specific risk and protective factors, it opens avenues for more precise disease understanding and management. The findings underline the importance of integrating genomics with metabolomics to fathom the multifaceted nature of GD.