Human Molecular Genetics, 2014, 01, 4433─4442

A Genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Korean

Kwak SH, Park YJ, Go MJ, Cho NH

Abstract

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 = 2.2E - 08). 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 = 1.3E - 010).
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 = 4.2E -07).
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

• ISBN or ISSN: 0964-6906

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N73002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N73002-00) by Research of Korea Centers for Disease Control and Prevention.