A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans.
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 = 2.2 × 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.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Soo Heon
SH
Kwak
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea Department of Internal Medicine.
Young Joo
YJ
Park
Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea.
Min Jin
MJ
Go
Department of Surgery, and.
Kyu Eun
KE
Lee
Department of Surgery, and.
Su-Jin
SJ
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Hoon Sung
HS
Choi
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Tae Hyuk
TH
Kim
Department of Internal Medicine, Department of Internal Medicine, and.
Sung Hee
SH
Choi
Department of Internal Medicine, Department of Internal Medicine, and.
Soo
S
Lim
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Korea Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.
Ki Woong
KW
Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea Department of Internal Medicine.
Do Joon
DJ
Park
Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea.
Sung Soo
SS
Kim
Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea.
Jong-Young
JY
Lee
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea Department of Internal Medicine, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea and.
Kyong Soo
KS
Park
Department of Internal Medicine, Department of Internal Medicine, and.
Hak C
HC
Jang
Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea chnaha@ajou.ac.kr.
Nam H
NH
Cho
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism*; D044466:Asian People; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007453:Iodide Peroxidase / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D000906:Antibodies; D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine