Sex-specific genetic influence on thyroidstimulating hormone and free thyroxine levels, and interactions between measurements

KNHANES 2013 2015

Young Ki Lee, Dong Yeob Shin, Hyejung Shin, Eunjig Lee

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Background Although a wide range of genetic influences on thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels have been reported, sex differences in the genetic influences have not been well described. Methods We assessed TSH and fT4 levels in 2,250 subjects without thyroid peroxidase antibody, with data obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2013 to 2015. Using variance decomposition methods, the variation of TSH and fT4 levels was divided into genetic and environmental components common to both sexes, and to males and females separately. The genetic correlation between TSH and fT4 levels was also assessed in both sexes, and in males and females separately. Results Narrow-sense heritability for TSH and fT4 were 54% and 56%, respectively. Sex-specific heritability for TSH levels was significantly higher in females than in males (75% and 41%, respectively; p = 0.037). Heritability for fT4 levels was not significantly different between males and females (62% and 52%, respectively; p = 0.335). TSH and fT4 levels showed a negative genetic correlation in females (pg =-0.347, p = 0.040) after regressing out the influences of environmental covariates, but this correlation was not present in males (pg =-0.160, p = 0.391). Conclusions The genetic influences on individual TSH levels were more prominent in females than in males. In addition, female-specific pleiotropy between TSH and fT4 might be a clue that this stronger genetic influences in females would mainly affect thyroid function per se, rather than other TSHrelated factors that do not primarily trigger the negative feedback loop between TSH and fT4.

Original languageEnglish
Article numbere0207446
JournalPloS one
Volume13
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

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National Health and Nutrition Examination Survey
thyrotropin
Nutrition Surveys
Thyrotropin
Korea
Nutrition
thyroxine
Thyroxine
Korean Peninsula
hormones
Health
Hormones
gender
heritability
genetic correlation
iodide peroxidase
Iodide Peroxidase
pleiotropy
thyroid function
gender differences

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{5c6acf3b8583466e99c1468aac679869,
title = "Sex-specific genetic influence on thyroidstimulating hormone and free thyroxine levels, and interactions between measurements: KNHANES 2013 2015",
abstract = "Background Although a wide range of genetic influences on thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels have been reported, sex differences in the genetic influences have not been well described. Methods We assessed TSH and fT4 levels in 2,250 subjects without thyroid peroxidase antibody, with data obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2013 to 2015. Using variance decomposition methods, the variation of TSH and fT4 levels was divided into genetic and environmental components common to both sexes, and to males and females separately. The genetic correlation between TSH and fT4 levels was also assessed in both sexes, and in males and females separately. Results Narrow-sense heritability for TSH and fT4 were 54{\%} and 56{\%}, respectively. Sex-specific heritability for TSH levels was significantly higher in females than in males (75{\%} and 41{\%}, respectively; p = 0.037). Heritability for fT4 levels was not significantly different between males and females (62{\%} and 52{\%}, respectively; p = 0.335). TSH and fT4 levels showed a negative genetic correlation in females (pg =-0.347, p = 0.040) after regressing out the influences of environmental covariates, but this correlation was not present in males (pg =-0.160, p = 0.391). Conclusions The genetic influences on individual TSH levels were more prominent in females than in males. In addition, female-specific pleiotropy between TSH and fT4 might be a clue that this stronger genetic influences in females would mainly affect thyroid function per se, rather than other TSHrelated factors that do not primarily trigger the negative feedback loop between TSH and fT4.",
author = "Lee, {Young Ki} and Shin, {Dong Yeob} and Hyejung Shin and Eunjig Lee",
year = "2018",
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Sex-specific genetic influence on thyroidstimulating hormone and free thyroxine levels, and interactions between measurements : KNHANES 2013 2015. / Lee, Young Ki; Shin, Dong Yeob; Shin, Hyejung; Lee, Eunjig.

In: PloS one, Vol. 13, No. 11, e0207446, 01.11.2018.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Sex-specific genetic influence on thyroidstimulating hormone and free thyroxine levels, and interactions between measurements

T2 - KNHANES 2013 2015

AU - Lee, Young Ki

AU - Shin, Dong Yeob

AU - Shin, Hyejung

AU - Lee, Eunjig

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background Although a wide range of genetic influences on thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels have been reported, sex differences in the genetic influences have not been well described. Methods We assessed TSH and fT4 levels in 2,250 subjects without thyroid peroxidase antibody, with data obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2013 to 2015. Using variance decomposition methods, the variation of TSH and fT4 levels was divided into genetic and environmental components common to both sexes, and to males and females separately. The genetic correlation between TSH and fT4 levels was also assessed in both sexes, and in males and females separately. Results Narrow-sense heritability for TSH and fT4 were 54% and 56%, respectively. Sex-specific heritability for TSH levels was significantly higher in females than in males (75% and 41%, respectively; p = 0.037). Heritability for fT4 levels was not significantly different between males and females (62% and 52%, respectively; p = 0.335). TSH and fT4 levels showed a negative genetic correlation in females (pg =-0.347, p = 0.040) after regressing out the influences of environmental covariates, but this correlation was not present in males (pg =-0.160, p = 0.391). Conclusions The genetic influences on individual TSH levels were more prominent in females than in males. In addition, female-specific pleiotropy between TSH and fT4 might be a clue that this stronger genetic influences in females would mainly affect thyroid function per se, rather than other TSHrelated factors that do not primarily trigger the negative feedback loop between TSH and fT4.

AB - Background Although a wide range of genetic influences on thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels have been reported, sex differences in the genetic influences have not been well described. Methods We assessed TSH and fT4 levels in 2,250 subjects without thyroid peroxidase antibody, with data obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2013 to 2015. Using variance decomposition methods, the variation of TSH and fT4 levels was divided into genetic and environmental components common to both sexes, and to males and females separately. The genetic correlation between TSH and fT4 levels was also assessed in both sexes, and in males and females separately. Results Narrow-sense heritability for TSH and fT4 were 54% and 56%, respectively. Sex-specific heritability for TSH levels was significantly higher in females than in males (75% and 41%, respectively; p = 0.037). Heritability for fT4 levels was not significantly different between males and females (62% and 52%, respectively; p = 0.335). TSH and fT4 levels showed a negative genetic correlation in females (pg =-0.347, p = 0.040) after regressing out the influences of environmental covariates, but this correlation was not present in males (pg =-0.160, p = 0.391). Conclusions The genetic influences on individual TSH levels were more prominent in females than in males. In addition, female-specific pleiotropy between TSH and fT4 might be a clue that this stronger genetic influences in females would mainly affect thyroid function per se, rather than other TSHrelated factors that do not primarily trigger the negative feedback loop between TSH and fT4.

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U2 - 10.1371/journal.pone.0207446

DO - 10.1371/journal.pone.0207446

M3 - Review article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e0207446

ER -