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

Purdey Campbell; Thomas H Brix; Scott G Wilson; Lynley C Ward; Jennie Hui; John P Beilby; Laszlo Hegedüs; John P Walsh

doi:10.1111/cen.12746

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

Clin Endocrinol (Oxf). 2016 Feb;84(2):278-283. doi: 10.1111/cen.12746. Epub 2015 Feb 27.

Authors

Purdey Campbell¹, Thomas H Brix², Scott G Wilson^{1

3

4}, Lynley C Ward¹, Jennie Hui⁵, John P Beilby^{5

6}, Laszlo Hegedüs², John P Walsh^{1

3}

Affiliations

¹ Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
² Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
³ School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
⁴ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
⁵ Pathwest Laboratory Medicine WA, Nedlands, WA, Australia.
⁶ School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.

PMID: 25683181
DOI: 10.1111/cen.12746

Abstract

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.