Genome-Wide Association Study of Temporomandibular Disorder-Related Pain in Finnish Populations

Temporomandibular disorders (TMD) are multifactorial musculoskeletal pain and dysfunctions in temporomandibular joints (TMJs) and masticatory muscles. Genetic factors play a role in TMD-related pain, but only a few genome-wide association studies (GWAS) have been conducted.

The aim of this GWAS was to explore genetic factors associated with painful TMD in Finnish populations.

Data from two epidemiological surveys, the Northern Finland Birth Cohort 1966 (NFBC1966) and the Health 2000 Survey in Finland, including altogether 468 cases and 6833 controls, were used. Case definition was based on pain on palpation of masticatory muscles and/or TMJs. GWASs of the whole data and stratified by sex were conducted from both cohorts using additive models, followed by meta-analysis of the two cohorts. Replications of the previously reported TMD risk loci (rs73460075, DMD; rs4794106, SGCA; rs73271865, SP4; rs60249166, RXP2; rs1531554, BAHCCI; rs5862730, OTUD4/SMAD1; rs10092633, SFRP1; rs34612513, SOX14/CLDN18; rs878962, TSPAN9) were also investigated.

Four genome-wide significant loci were found in sex-stratified analysis of NFBC1966, including associations at three loci in males (rs1023114, PRIM2, p = 5 × 10^-9; rs4244867, ALG10, p = 3 × 10^-8; rs79841648, ADCYAP1, p = 4 × 10^-9) and one locus in females (rs148476652, DNER, p = 4 × 10^-9). However, the results could not be replicated in the Health 2000 Survey or in the meta-analysis of these two cohorts. The previous TMD GWAS associations did not replicate in our data either.

Several TMD pain-associated variants were found in sex-stratified analysis of NFBC1966, suggesting the role of neuroendocrine stress responses and central nervous system. These findings need to be confirmed in future studies.