title: Common genetic variants associated with thyroid function may be risk alleles for Hashimoto's disease and Graves' disease.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Common variants in PDE10A and MAF gene regions may influence whether patients with AITD develop Graves' disease or Hashimoto's disease.
authors: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors: Purdey
authors: P
authors: Campbell
authors: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
authors: Thomas H
authors: TH
authors: Brix
authors: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.|School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.|Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors: Scott G
authors: SG
authors: Wilson
authors: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors: Lynley C
authors: LC
authors: Ward
authors: Pathwest Laboratory Medicine WA, Nedlands, WA, Australia.
authors: Jennie
authors: J
authors: Hui
authors: Pathwest Laboratory Medicine WA, Nedlands, WA, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.
authors: John P
authors: JP
authors: Beilby
authors: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
authors: Laszlo
authors: L
authors: Hegedüs
authors: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.|School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia.
authors: John P
authors: JP
authors: Walsh