SynthesisPain2019
Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.
Synthesis in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Temporomandibular disorder prevalence in malocclusion patients: a meta-analysis.Head & face medicine · 2025Pooled it
- Epigenetic and biomolecular mechanisms in chronic temporomandibular disorder-related pain: an integrative review.Molecular biology reports · 2026Review
- Genetic subtraction reveals divergent pathways and targets in anxiety-related and anxiety-independent TMD.The journal of headache and pain · 2026Article
- Genome-Wide Association Study of Temporomandibular Disorder-Related Pain in Finnish Populations.Journal of oral rehabilitation · 2025Article
- Hierarchical selection of genetic and gene by environment interaction effects in high-dimensional mixed models.Statistical methods in medical research · 2025Review
- Investigating the impact of polymorphisms in theFrontiers in oral health · 2025Article
- Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD.Discover oncology · 2024Article
- Polygenic Contributions to Chronic Overlapping Pain Conditions in a Large Electronic Health Record Sample.The journal of pain · 2023Article
- Genetic overlap between temporomandibular disorders and primary headaches: A systematic review.The Japanese dental science review · 2022Review
- The Chinese version of the Oral Health Impact Profile-14 (OHIP-14) questionnaire among college students: factor structure and measurement invariance across genders.BMC oral health · 2022Article
- Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.Neuron · 2022Article
- Sex differences in pain along the neuraxis.Neuropharmacology · 2022Review
- Transcriptomic Analysis of Trigeminal Ganglion and Spinal Trigeminal Nucleus Caudalis in Mice with Inflammatory Temporomandibular Joint Pain.Journal of pain research · 2022Article
- Considering strategies for SNP selection in genetic and polygenic risk scores.Frontiers in genetics · 2022Article
- BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint.Cartilage · 2021Article
- Genome-wide association study identifiesAnnals of the rheumatic diseases · 2021Article
- Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain.Nature communications · 2021Article
- The Need to Consider Pregnancy As a Biological Variable to Reduce Preventable Suffering Related to Pregnancy.Journal of women's health (2002) · 2021Article
- Article
- Qualitative sex differences in pain processing: emerging evidence of a biased literature.Nature reviews. Neuroscience · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
41 authors at 19 institutions in 7 countries.
Funding
Abstract
Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43 × 10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.