Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease

P. Campbell, T.H. Brix, Scott Wilson, L.C. Ward, J. Hui, John Beilby, L. Hegedüs, John Walsh

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Abstract

© 2015 John Wiley & Sons Ltd. Background Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. Objective To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. Patients and measurements We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. Results For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10-4) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10-4) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10-6); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Conclusion Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease.
Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalClinical Endocrinology
Volume84
Issue number2
Early online date19 Jan 2016
DOIs
Publication statusPublished - 27 Feb 2016

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Hashimoto Disease
Graves Disease
Thyroid Gland
Alleles
Thyroid Diseases
Gene Frequency
Autoimmune Diseases
Iodide Peroxidase
Nuclear Family
Smoking
Antibodies
Genes

Cite this

@article{6446a70690cb4a28b4815dc4aa86b35a,
title = "Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease",
abstract = "{\circledC} 2015 John Wiley & Sons Ltd. Background Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. Objective To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. Patients and measurements We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. Results For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10-4) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10-4) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10-6); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Conclusion Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease.",
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Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease. / Campbell, P.; Brix, T.H.; Wilson, Scott; Ward, L.C.; Hui, J.; Beilby, John; Hegedüs, L.; Walsh, John.

In: Clinical Endocrinology, Vol. 84, No. 2, 27.02.2016, p. 278-283.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease

AU - Campbell, P.

AU - Brix, T.H.

AU - Wilson, Scott

AU - Ward, L.C.

AU - Hui, J.

AU - Beilby, John

AU - Hegedüs, L.

AU - Walsh, John

PY - 2016/2/27

Y1 - 2016/2/27

N2 - © 2015 John Wiley & Sons Ltd. Background Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. Objective To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. Patients and measurements We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. Results For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10-4) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10-4) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10-6); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Conclusion Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease.

AB - © 2015 John Wiley & Sons Ltd. Background Recent studies have identified common genetic variants associated with TSH, free T4 and thyroid peroxidase antibodies, but it is unclear whether these differ between patients with Hashimoto's disease and Graves' disease. Objective To examine whether 11 common genetic variants differ between Graves' disease and Hashimoto's disease. Patients and measurements We genotyped 11 common variants in a discovery cohort of 203 Australian patients with autoimmune thyroid disease (AITD). Two variants with significant or suggestive associations were analysed in a replication cohort of 384 Danish patients. Results For rs753760 (PDE10A), the minor allele frequency in Graves' disease and Hashimoto's disease was 0·38 vs. 0·23, respectively, (P = 6·42 × 10-4) in the discovery cohort, 0·29 vs. 0·24 (P = 0·147) in the replication cohort and 0·32 vs. 0·24 in combined analysis (P = 0·0021; all analyses adjusted for sex). In healthy controls from Busselton, the frequency was 0·29, significantly different from Hashimoto's disease but not Graves' disease. For rs4889009 (MAF gene region), the frequency of the minor G-allele in Graves' disease and Hashimoto's disease was 0·48 vs. 0·36 (P = 0·0156) in the discovery cohort, 0·48 vs. 0·34 (P = 1·83 × 10-4) in the replication cohort and 0·48 vs. 0·35 in the combined analysis (P = 7·53 × 10-6); in controls, the frequency was 0·38, significantly different from Graves' disease but not Hashimoto's disease. After further adjustment for smoking, associations with rs4889009 remained significant, whereas those with rs753760 were not. Conclusion Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease.

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DO - 10.1111/cen.12746

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VL - 84

SP - 278

EP - 283

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 2

ER -