title: Genetic analysis in young-age-of-onset Graves' disease reveals new susceptibility loci.
abstract: BACKGROUND
  Genetic and environmental factors play an essential role in the pathogenesis of Graves' Disease (GD). Children with GD have less exposure time to environmental factors and therefore are believed to harbor stronger genetic susceptibility than adults.
  
  
  OBJECTIVE
  The aim of the study was to identify susceptibility loci that predispose to GD in patients with young-age-of-onset (YAO) GD.
  
  
  METHODS
  One hundred six patients with YAO GD (onset <30 y) and 855 healthy subjects were studied. Cases and controls were genotyped using the Illumina Infinium Immunochip, designed to genotype 196,524 polymorphisms. Case control association analyses were performed using the PLINK computer package. Ingenuity Pathway Analysis program (QIAGEN) was used to carry out pathway analyses.
  
  
  RESULTS
  Immunochip genetic association analysis identified 30 single-nucleotide polymorphisms in several genes that were significantly associated with YAO GD, including major histocompatibility complex class I and class II genes, BTNL2, NOTCH4, TNFAIP3, and CXCR4. Candidate gene analysis revealed that most of the genes previously shown to be associated with adult-onset GD were also associated with YAO GD. Pathway analysis demonstrated that antigen presentation, T-helper cell differentiation, and B cell development were the major pathways contributing to the pathogenesis of YAO GD.
  
  
  CONCLUSIONS
  Genetic analysis identified novel susceptibility loci in YAO GD adding a new dimension to the understanding of GD etiology.
authors.affiliation: Division of Endocrinology (R.B., J.G.), Children's Hospital of Boston, Boston, Massachusetts 02115; Division of Endocrinology (A.L., A.H., E.C., S.S.H., Y.T.), Icahn School of Medicine at Mt Sinai, New York, New York 10029; Battelle Center for Mathematical Medicine (D.G.), Nationwide Children's Hospital, Columbus, Ohio 43210; Department of Medicine Bioinformatics Core (V.L., W.Z.), Mount Sinai School of Medicine, New York, New York 10029; and James J. Peters VA Medical Center, Bronx (Y.T.), New York, New York 10468.
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Brown
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardi
authors.forename: Alia
authors.initials: A
authors.lastname: Hasham
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
authors.forename: Joshua
authors.initials: J
authors.lastname: Gordon
authors.forename: Erlinda
authors.initials: E
authors.lastname: Concepcion
authors.forename: Sara S
authors.initials: SS
authors.lastname: Hammerstad
authors.forename: Vaneet
authors.initials: V
authors.lastname: Lotay
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Yaron
authors.initials: Y
authors.lastname: Tomer
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D055815:Young Adult