Genome‐wide association study of degenerative bony changes of the temporomandibular joint

Objectives To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint ( TMJ ). Materials and 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 E ast A sian populations using an I llumina H uman O mni E xpress B ead C hip. After rigorous quality‐control filtering, approximately 550 000 single nucleotide polymorphisms ( SNP s) were used for tests of associations with disease status. Results Forty‐one SNP s at 22 independent loci showed association signals at P  <   1 × 10 −4 . The SNP rs878962, which maps on an intron of TSPAN 9 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 SNP s, two intronic SNP s of APOL 3 (rs80575) and MRC 2 (rs2460300) may fall within regulatory elements and affect DNA –protein interactions. We could not replicate SNP s 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.