title: Genome-wide association study of degenerative bony changes of the temporomandibular joint.
abstract: OBJECTIVE
  To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint (TMJ).
  
  
  METHODS
  Bony changes of the TMJ condylar head were diagnosed by examination of panoramic radiographs and/or magnetic resonance images and/or computed tomography images. We conducted a genome-wide association study (GWAS) of 146 cases with TMJ degeneration and 374 controls from East Asian populations using an Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550,000 single nucleotide polymorphisms (SNPs) were used for tests of associations with disease status.
  
  
  RESULTS
  Forty-one SNPs at 22 independent loci showed association signals at P < 1 × 10(-4). The SNP rs878962, which maps on an intron of TSPAN9 on chromosome 12, showed the strongest association (combined OR = 1.89, 95% confidence interval = 1.43-2.50, P = 8.1 × 10(-6)). According to in silico predictions of the 41 SNPs, two intronic SNPs of APOL3 (rs80575) and MRC2 (rs2460300) may fall within regulatory elements and affect DNA-protein interactions. We could not replicate SNPs located on genes that have been reported to be associated with temporomandibular disorder or temporomandibular osteoarthritis in previous studies at P < 1 × 10(-4).
  
  
  CONCLUSIONS
  Our GWAS identified 22 independent loci showing suggestive association signals with degenerative bony changes of the TMJ. These loci provide good candidates for future follow-up studies.
authors.affiliation: Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Nakaoka
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Y-I
authors.initials: YI
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: S
authors.initials: S
authors.lastname: Haga
authors.forename: K
authors.initials: K
authors.lastname: Katayama
authors.forename: T
authors.initials: T
authors.lastname: Shibusawa
authors.forename: S B
authors.initials: SB
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Maki
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.forename: I
authors.initials: I
authors.lastname: Inoue
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013705:Temporomandibular Joint Disorders / Q000235:genetics*; D055815:Young Adult
keywords: degeneration; genome-wide association study (GWAS); osteoarthritis; temporo-mandibular joint (TMJ)