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Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study.

Publication ,  Journal Article
Smith, SB; Mir, E; Bair, E; Slade, GD; Dubner, R; Fillingim, RB; Greenspan, JD; Ohrbach, R; Knott, C; Weir, B; Maixner, W; Diatchenko, L
Published in: J Pain
December 2013

UNLABELLED: Genetic risk factors are believed to combine with environmental exposures and contribute to the risk of developing temporomandibular disorder (TMD). In this prospective cohort study, 2,737 people without TMD were assessed for common genetic variation in 358 genes known to contribute to nociceptive pathways, inflammation, and affective distress. During a median follow-up period of 2.8 years, 260 people developed first-onset TMD. Hazard ratios were computed as measures of association between 2,924 single-nucleotide polymorphisms and TMD incidence. After correction for multiple testing, no single single-nucleotide polymorphism was significantly associated with risk of onset TMD. However, several single-nucleotide polymorphisms exceeded Bonferroni correction for multiple comparison or false discovery rate thresholds (.05, .1, or .2) for association with intermediate phenotypes shown to be predictive of TMD onset. Nonspecific orofacial symptoms were associated with voltage-gated sodium channel, type I, alpha subunit (SCN1A, rs6432860, P = 2.77 × 10(-5)) and angiotensin I-converting enzyme 2 (ACE2, rs1514280, P = 4.86 × 10(-5)); global psychological symptoms with prostaglandin-endoperoxide synthase 1 (PTGS1, rs3842803, P = 2.79 × 10(-6)); stress and negative affectivity with amyloid-β (A4) precursor protein (APP, rs466448, P = 4.29 × 10(-5)); and heat pain temporal summation with multiple PDZ domain protein (MPDZ, rs10809907, P = 3.05 × 10(-5)). The use of intermediate phenotypes for complex pain diseases revealed new genetic pathways influencing risk of TMD. PERSPECTIVE: This article reports the findings of a large candidate gene association study of first-onset TMD and related intermediate phenotypes in the OPPERA Study. Although no genetic markers predicted TMD onset, several genetic risk factors for clinical, psychological, and sensory phenotypes associated with TMD onset were observed.

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Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

December 2013

Volume

14

Issue

12 Suppl

Start / End Page

T91-101.e1-3

Location

United States

Related Subject Headings

  • Temporomandibular Joint Disorders
  • Risk Factors
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Female
 

Citation

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Smith, S. B., Mir, E., Bair, E., Slade, G. D., Dubner, R., Fillingim, R. B., … Diatchenko, L. (2013). Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study. J Pain, 14(12 Suppl), T91-101.e1-3. https://doi.org/10.1016/j.jpain.2013.09.004
Smith, Shad B., Ellen Mir, Eric Bair, Gary D. Slade, Ronald Dubner, Roger B. Fillingim, Joel D. Greenspan, et al. “Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study.J Pain 14, no. 12 Suppl (December 2013): T91-101.e1-3. https://doi.org/10.1016/j.jpain.2013.09.004.
Smith SB, Mir E, Bair E, Slade GD, Dubner R, Fillingim RB, et al. Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study. J Pain. 2013 Dec;14(12 Suppl):T91-101.e1-3.
Smith, Shad B., et al. “Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study.J Pain, vol. 14, no. 12 Suppl, Dec. 2013, pp. T91-101.e1-3. Pubmed, doi:10.1016/j.jpain.2013.09.004.
Smith SB, Mir E, Bair E, Slade GD, Dubner R, Fillingim RB, Greenspan JD, Ohrbach R, Knott C, Weir B, Maixner W, Diatchenko L. Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study. J Pain. 2013 Dec;14(12 Suppl):T91-101.e1–3.
Journal cover image

Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

December 2013

Volume

14

Issue

12 Suppl

Start / End Page

T91-101.e1-3

Location

United States

Related Subject Headings

  • Temporomandibular Joint Disorders
  • Risk Factors
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Female