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

Soo Heon Kwak, Young Joo Park, Min Jin Go, Kyu Eun Lee, Su Jin Kim, Hoon Sung Choi, Tae Hyuk Kim, Sung HeeChoi, Soo Lim, Ki Woong Kim, Do Joon Park, Sung Soo Kim, Jong Young Lee, Kyong Soo Park, Hak C. Jang, Nam H. Cho

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13 Citations (Scopus)

Abstract

Genetic factors are thought to be an important determinant of thyroid function and auto immunity. 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 TPOmRNA 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.

Original languageEnglish
Article numberddu145
Pages (from-to)4433-4442
Number of pages10
JournalHuman Molecular Genetics
Volume23
Issue number16
DOIs
StatePublished - Aug 2014

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Iodide Peroxidase
Genome-Wide Association Study
Thyroid Gland
Thyrotropin
Antibodies
Joints
Thyroxine
Longitudinal Studies
Meta-Analysis
Immunity
Alleles
Genome
Health

Cite this

@article{2886565026854aadb87062da5d39b3b4,
title = "A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans",
abstract = "Genetic factors are thought to be an important determinant of thyroid function and auto immunity. 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 TPOmRNA 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.",
author = "Kwak, {Soo Heon} and Park, {Young Joo} and Go, {Min Jin} and Lee, {Kyu Eun} and Kim, {Su Jin} and Choi, {Hoon Sung} and Kim, {Tae Hyuk} and Sung HeeChoi and Soo Lim and Kim, {Ki Woong} and Park, {Do Joon} and Kim, {Sung Soo} and Lee, {Jong Young} and Park, {Kyong Soo} and Jang, {Hak C.} and Cho, {Nam H.}",
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A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans. / Kwak, Soo Heon; Park, Young Joo; Go, Min Jin; Lee, Kyu Eun; Kim, Su Jin; Choi, Hoon Sung; Kim, Tae Hyuk; HeeChoi, Sung; Lim, Soo; Kim, Ki Woong; Park, Do Joon; Kim, Sung Soo; Lee, Jong Young; Park, Kyong Soo; Jang, Hak C.; Cho, Nam H.

In: Human Molecular Genetics, Vol. 23, No. 16, ddu145, 08.2014, p. 4433-4442.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans

AU - Kwak, Soo Heon

AU - Park, Young Joo

AU - Go, Min Jin

AU - Lee, Kyu Eun

AU - Kim, Su Jin

AU - Choi, Hoon Sung

AU - Kim, Tae Hyuk

AU - HeeChoi, Sung

AU - Lim, Soo

AU - Kim, Ki Woong

AU - Park, Do Joon

AU - Kim, Sung Soo

AU - Lee, Jong Young

AU - Park, Kyong Soo

AU - Jang, Hak C.

AU - Cho, Nam H.

PY - 2014/8

Y1 - 2014/8

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AB - Genetic factors are thought to be an important determinant of thyroid function and auto immunity. 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 TPOmRNA 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.

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DO - 10.1093/hmg/ddu145

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