Leppilahti J M, Knuutila J, Pesonen P, Vuollo V, Männikkö M, Karjalainen M K, Suominen A L, Sipilä K
Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
Northern Finland Birth Cohorts, Arctic Biobank, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland.
J Oral Rehabil. 2025 Feb;52(2):151-159. doi: 10.1111/joor.13883. Epub 2024 Oct 31.
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; rs4244867, ALG10, p = 3 × 10; rs79841648, ADCYAP1, p = 4 × 10) and one locus in females (rs148476652, DNER, p = 4 × 10). 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.
颞下颌关节紊乱病（TMD）是颞下颌关节（TMJ）和咀嚼肌的多因素肌肉骨骼疼痛及功能障碍。遗传因素在TMD相关疼痛中起作用，但仅开展了少数全基因组关联研究（GWAS）。
本GWAS的目的是探索芬兰人群中与疼痛性TMD相关的遗传因素。
使用了两项流行病学调查的数据，即1966年芬兰北部出生队列（NFBC1966）和芬兰2000年健康调查，共包括468例病例和6833例对照。病例定义基于咀嚼肌和/或TMJ触诊疼痛。对两个队列的全部数据按性别分层，使用加性模型进行GWAS，随后对两个队列进行荟萃分析。还对先前报道的TMD风险位点（rs73460075，DMD；rs4794106，SGCA；rs73271865，SP4；rs60249166，RXP2；rs1531554，BAHCCI；rs5862730，OTUD4/SMAD1；rs10092633，SFRP1；rs34612513，SOX14/CLDN18；rs878962，TSPAN9）进行了重复研究。
在NFBC1966的性别分层分析中发现了4个全基因组显著位点，包括男性3个位点的关联（rs1023114，PRIM2，p = 5×10；rs4244867，ALG10，p = 3×10；rs79841648，ADCYAP1，p = 4×10）和女性1个位点的关联（rs148476652，DNER，p = 4×10）。然而，这些结果在2000年健康调查或这两个队列的荟萃分析中未能得到重复验证。先前的TMD GWAS关联在我们的数据中也未得到重复验证。
在NFBC1966的性别分层分析中发现了几个与TMD疼痛相关的变异，提示神经内分泌应激反应和中枢神经系统的作用。这些发现需要在未来的研究中得到证实。
