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 (fT4) 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 5 2.2 3 1028). 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 5 1.3 3 10210).

This varianthadamarginal sex-specific effect,andits associationwasmore significant in females. Subjects possessing

the rs2071403A allele, associated with an absence of the anti-TPO antibody, had decreased TPOmRNA

expression in their thyroid tissue. Another intronic variant ofHLA-DPB2, rs733208,hadasuggestive association

with anti-TPO antibody positivity (P 5 4.2 3 1027). 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.​