A Genome-Wide Association Study on Thyroid Function and Anti-Thyroid Peroxidase Antibody in Koreans

Presentation Number: SAT-0561
Date of Presentation: June 21st, 2014

Soo Heon Kwak1, Ye An Kim*2, Kyu Eun Lee2, Hoonsung Choi3, Tae Hyuk Kim2, Sung Hee Choi4, Soo Lim5, Ki Woong Kim2, Do Joon Park2, Kyong Soo Park6, Hak Chul Jang7 and Young Joo Park2
1Seoul National University Hospital, 2Seoul National University College of Medicine, Seoul, Korea, Republic of (South), 3Seoul National Univ Coll of Med, Seoul, Korea, Republic of (South), 4Seoul Nat Univ Bundang Hosp, Seongnam-Si, Korea, Republic of (South), 5Seoul National University Bundang Hospital, Seongnam, Korea, Republic of (South), 6Seoul Natl Univ Hosp, Seoul, Korea, Republic of (South), 7Seoul National University Bundang, Seongnam-Si, Korea, Republic of (South)


Genetic factors are thought to be an important determinant of thyroid function and autoimmunity. However, there are limited data on theses genetic variants in Asians. In this study, we performed a two-staged genome-wide association study on plasma thyroid stimulating hormone (TSH) and free thyroxin (fT4) concentration, and anti-thyroid peroxidase (anti-TPO) antibody positivity in up to 4,238 Korean subjects. In the stage 1 genome scan, 3,396 participants from Ansung cohort were investigated using 1.42 million genotyped or imputed markers. In the stage 2 follow-up, 10 makers were de novo genotyped in 842 participants form the Korean Longitudinal Study on Health and Aging study. An intronic variant in VAV3, rs12126655, which was reported in Europeans, was significantly associated with plasma TSH concentration in the joint stage 1 and 2 analysis (P=2.2 10-8). We found that a novel variant, rs2071403, located at 75 base-pair proximal to the translational start site of TPO was significantly associated with plasma anti-TPO antibody positivity in the joint stage 1 and 2 analysis (P=1.3 10-10). This variant had a nominal sex specific effect and its association was more significant in females. Subjects who had rs2071403A allele, which was associated with absence of 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 strongly associated with TSH level and anti-TPO antibody positivity in Koreans.


Nothing to Disclose: SHK, YAK, KEL, HC, THK, SHC, SL, KWK, DJP, KSP, HCJ, YJP