Genetic Prediction of Causal Association Between Celiac Disease and Thyroid Function: A Two-Sample Mendelian Randomized Study.

Abstract

Aim: Observational studies have suggested an association between celiac disease and thyroid dysfunction, but their causal relationship has not yet been established.

Methods: Summary statistics for celiac disease were retrieved from the FinnGen Consortium, thyroid hormone and antibody data were obtained from the ThyroidOmics Consortium, and genetic variants associated with hyperthyroidism and hypothyroidism were sourced from the UK Biobank. MR statistical analyses used the inverse variance weighted algorithm, followed by various sensitivity analyses and reliability evaluations.

Results: Genetic proxied celiac disease was significantly associated with increased free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) levels and decreased free triiodothyronine (FT3)/FT4 ratio, whereas the causality of this common enteropathy on thyroid stimulating hormone (TSH), FT3, total triiodothyronine (TT3), and TT3/FT4 ratio (and vice versa) is unfounded. Moreover, the findings of MR analysis tend to favor the causality of celiac disease for hyperthyroidism, but not hypothyroidism.

Conclusion: By leveraging large GWAS consortia datasets, our MR study indicates that the genetic liability to celiac disease is suggestively detrimental to the homeostasis of FT4 and TPOAb levels and FT3/FT4 ratio. Our findings provide caution regarding the risk of hyperthyroidism but not hypothyroidism for individuals suffering from celiac disease.