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Apoptosis-antagonizing transcription factor AATF and chromatinremodeling SMARCA2 are associated with thyroid volume in Hashimoto's thyroiditis patients

Thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT). To explore genetic background of thyroid antibodies, we performed the first genome-wide association study (GWAS) of thyroid antibodies levels in 405 HT patients. GWAS analyses on TgAb and TPOAb levels were performed separately on a set of 6 007 542 genetic variants using GEMMA. To identify genetic variants that predispose to both thyroid antibodies, we additionally performed a bivariate analysis using MultiABEL. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P=2.34×10-7 ) and rs756763 inside CA10 (P=6.05×10-7 ) ; one with TPOAb, rs12507813 between TRIM61 and TRIM60 (P=4.95×10-7 ) ; and three with both antibodies (bivariate analysis), rs13190616 inside RP11- 138J23.1 (P=2.01×10-6 ), rs561030786 close to DUBR (P=7.33×10-6 ) and rs12713034 inside FSHR (P=7.66×10-6 ). All identified genomic regions have a substantial literature record of involvement with female-related traits, immunemediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and several non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function.

thyroid volume, Hashimoto's thyroiditis, AATF, SMARCA2

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