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

Area of Science:

• Endocrinology
• Gastroenterology
• Genetics

Background:

• Observational studies suggest a link between celiac disease and thyroid dysfunction.
• The causal relationship between celiac disease and thyroid disorders remains unclear.

Purpose of the Study:

• To investigate the potential causal relationship between celiac disease and thyroid dysfunction using a Mendelian randomization (MR) approach.
• To analyze the impact of genetic liability to celiac disease on various thyroid hormone levels and antibodies.

Main Methods:

• Utilized summary statistics from large genome-wide association studies (GWAS) consortia: FinnGen, ThyroidOmics, and UK Biobank.
• Employed the inverse variance weighted (IVW) algorithm for MR analysis, supplemented with sensitivity analyses.

Main Results:

• Genetic liability for celiac disease was associated with elevated free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) levels.
• A decreased free triiodothyronine (FT3)/FT4 ratio was observed, suggesting an impact on thyroid hormone homeostasis.
• MR analysis indicated a potential causal effect of celiac disease on hyperthyroidism, but not hypothyroidism.

Conclusions:

• Genetic predisposition to celiac disease may negatively influence FT4 and TPOAb levels and the FT3/FT4 ratio.
• Individuals with celiac disease should be monitored for an increased risk of hyperthyroidism.
• The study provides evidence suggesting celiac disease is not causally linked to hypothyroidism.