Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis

Area of Science:

• Genetics
• Immunology
• Endocrinology

Background:

• Hashimoto's thyroiditis (HT) is the predominant autoimmune thyroid disease.
• Current understanding of HT genetic factors remains limited.
• No genome-wide association study (GWAS) has exclusively focused on HT previously.

Purpose of the Study:

• To conduct the first GWAS for Hashimoto's thyroiditis.
• To identify novel genetic determinants of HT.
• To investigate genetic susceptibility in a Croatian population.

Main Methods:

• A genome-wide association study (GWAS) was performed on 405 HT cases and 433 controls.
• Thirteen significant signals (P < 10^-5) were selected for replication.
• Meta-analysis combined discovery and replication cohort data (total 1443 individuals).

Main Results:

• Three suggestive variants associated with HT were identified: rs12944194 (near SDK2), rs75201096 (in GNA14), and rs791903 (in IP6K3).
• A genetic risk score (GRS) using these variants explained 4.82% of HT variance.
• The top GRS quartile showed 2.76 times higher odds of HT compared to the lowest quartile.

Conclusions:

• The identified loci represent novel genetic factors implicated in HT susceptibility.
• Genomic regions associated with these loci are biologically plausible, relating to thyroid function and autoimmunity.
• Genetic overlap was observed between HT and related conditions like hypothyroidism and Graves' disease.