title: Fine mapping of loci linked to autoimmune thyroid disease identifies novel susceptibility genes.
abstract: BACKGROUND
  Genetic factors play a major role in the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). We have previously identified three loci on chromosomes 10q, 12q, and 14q that showed strong linkage with AITD, HT, and GD, respectively.
  
  
  OBJECTIVE
  The objective of the study was to identify the AITD susceptibility genes at the 10q, 12q, and 14q loci.
  
  
  METHODS
  Three hundred forty North American Caucasian AITD patients and 183 healthy controls were studied. The 10q, 12q, and 14q loci were fine mapped by genotyping densely spaced single-nucleotide polymorphisms (SNPs) using the Illumina GoldenGate genotyping platform. Case control association analyses were performed using the UNPHASED computer package. Associated SNPs were reanalyzed in a replication set consisting of 238 AITD patients and 276 controls.
  
  
  RESULTS
  Fine mapping of the AITD locus, 10q, showed replicated association of the AITD phenotype (both GD and HT) with SNP rs6479778. This SNP was located within the ARID5B gene recently reported to be associated with rheumatoid arthritis and GD in Japanese. Fine mapping of the GD locus, 14q, revealed replicated association of the GD phenotype with two markers, rs12147587 and rs2284720, located within the NRXN3 and TSHR genes, respectively.
  
  
  CONCLUSIONS
  Fine mapping of three linked loci identified novel susceptibility genes for AITD. The discoveries of new AITD susceptibility genes will engender a new understanding of AITD etiology.
authors.affiliation: Department of Medicine, Division of Endocrinology, Mount Sinai School of Medicine, New York, New York 10029, USA. yaron.tomer@mssm.edu
authors.forename: Yaron
authors.initials: Y
authors.lastname: Tomer
authors.forename: Alia
authors.initials: A
authors.lastname: Hasham
authors.forename: Terry F
authors.initials: TF
authors.lastname: Davies
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stefan
authors.forename: Erlinda
authors.initials: E
authors.lastname: Concepcion
authors.forename: Mehdi
authors.initials: M
authors.lastname: Keddache
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000502:physiology; D013959:Thyroid Diseases / Q000235:genetics*; D013967:Thyroiditis, Autoimmune / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D011989:Receptors, Thyrotropin; D014157:Transcription Factors; C082354:neurexin IIIalpha