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Genetic factors are thought to be an important determinant of thyroid function and autoimmunity. However, there are limited data on genetic variants in Asians. In this study, we performed a genome-wide association study on plasma thyroid-stimulating hormone (TSH) and free thyroxine (fT 4 ) concentration and anti-thyroid peroxidase (anti-TPO) antibody positivity in 4238 Korean subjects. In the Stage 1 genome scan, 3396 participants from the Ansung cohort were investigated using 1.42 million genotyped or imputed markers. In the Stage 2 follow-up, 10 markers were genotyped in 842 participants from the Korean Longitudinal Study on Health and Aging cohort. An intronic variant in  VAV3,  rs12126655, which has been reported in Europeans, was significantly associated with plasma TSH concentration in the joint Stages 1 and 2 analyses ( P  = 2.2 × 10 −8 ). We observed that a novel variant, rs2071403, located 75 bp proximal to the translational start site of  TPO  was significantly associated with plasma anti-TPO antibody positivity in the joint Stages 1 and 2 analyses ( P  = 1.3 × 10 −10 ). This variant had a marginal sex-specific effect, and its association was more significant in females. Subjects possessing the rs2071403A allele, associated with an absence of the anti-TPO antibody, had decreased TPO mRNA expression in their thyroid tissue. Another intronic variant of  HLA-DPB2 , rs733208, had a suggestive association with anti-TPO antibody positivity ( P  = 4.2 × 10 −7 ). In conclusion, we have identified genetic variants that are strongly associated with TSH level and anti-TPO antibody positivity in Koreans. Further replications and meta-analysis are required to confirm these findings.

A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans