Genome-wide analysis identifies two susceptibility loci for positive thyroid peroxidase and thyroglobulin antibodies.

Abstract

INTRODUCTION\nThyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic influence; however, genetic factors that determine thyroid antibody positivity are largely unknown.\n\n\nMATERIALS AND METHODS\nTo identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2 613 individuals from Croatia. Participants with elevated plasma TPO-Ab and/or Tg-Ab were defined as cases (N = 619) and those with TPO-Ab and Tg-Ab within reference values were defined as controls (N =1 994).\n\n\nRESULTS\nWe identified two novel loci, of which one is located within the YES1 gene (rs77284350,P=1.50×10-8), and the other resides within the IRF8 gene (rs16939945, P=5.04×10-8).\n\n\nCONCLUSIONS\nAlthough the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research.