Dataset Information

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

ABSTRACT: Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10-8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10-8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10-8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10-7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

SUBMITTER: Sanders AE

PROVIDER: S-EPMC5298397 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Sanders A E AE Jain D D Sofer T T Kerr K F KF Laurie C C CC Shaffer J R JR Marazita M L ML Kaste L M LM Slade G D GD Fillingim R B RB Ohrbach R R Maixner W W Kocher T T Bernhardt O O Teumer A A Schwahn C C Sipilä K K Lähdesmäki R R Männikkö M M Pesonen P P Järvelin M M Rizzatti-Barbosa C M CM Meloto C B CB Ribeiro-Dasilva M M Diatchenko L L Serrano P P Smith S B SB

Journal of dental research 20170112 3

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms ( ...[more]

PMID: 28081371

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Project description:Rationale & objectiveRecent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented.Study designObservational cohort.Setting & participantsWe analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline.PredictorsPredictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition (<21 permanent teeth present).OutcomesOutcomes were incident low estimated glomerular filtration rate (eGFR) (eGFR <60 mL/min/1.73 m2 and decline in eGFR ≥1 mL/min/year); incident albuminuria (urine albumin:creatinine ratio [ACR] ≥30 mg/g); and change in eGFR and ACR.Analytic approachPoisson and linear regression.ResultsFor the sample (n = 7.732), baseline mean age was 41.5 years, 45.2% were male, 11.7% had ≥30% of sites with clinical attachment loss ≥3 mm, 5.1% had ≥30% of sites with probing depth ≥4 mm, 30.7% had ≥50% of sites with bleeding on probing, and 16.2% had absent functional dentition. During a median follow-up of 5.9 years, 149 patients developed low eGFR and 415 patients developed albuminuria. On multivariable analysis, presence versus absence of ≥30% of sites with probing depth ≥4 mm and absence of functional dentition were each associated with increased risk for incident low eGFR (incident density ratio, 2.31; 95% CI, 1.14-4.65 and 1.65, 95% CI, 1.01-2.70, respectively). None of the other predictors were associated with outcomes.LimitationsOnly a single kidney function follow-up measure.ConclusionsIn this cohort of US Hispanics/Latinos, we found that select measures of periodontal disease were associated with incident low eGFR. Future work is needed to assess whether the treatment of periodontal disease may prevent CKD.

Dataset Information

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Publications

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

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