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

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Title: GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.
Author(s): Sanders, AE
Jain, D
Sofer, T
Kerr, KF
Laurie, CC
Shaffer, JR
Marazita, ML
Kaste, LM
Slade, GD
Fillingim, RB
Ohrbach, R
Maixner, W
Kocher, T
Bernhardt, O
Teumer, A
Schwahn, C
Sipilä, K
Lähdesmäki, R
Männikkö, M
Pesonen, P
Järvelin, M
Rizzatti-Barbosa, CM
Meloto, CB
Ribeiro-Dasilva, M
Diatchenko, L
Serrano, P
Smith, SB
Item Type: Journal Article
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 × 10(6)) 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.
Publication Date: 12-Jan-2017
Date of Acceptance: 1-Jan-2017
ISSN: 0022-0345
Publisher: SAGE Publications
Start Page: 277
End Page: 284
Journal / Book Title: Journal of Dental Research
Volume: 96
Issue: 3
Copyright Statement: © 2017 International & American Associations for Dental Research. The final, definitive version of this paper has been published in Journal of Dental Research 2017, Vol. 96(3) 277–284 by Sage Publications Ltd. All rights reserved. It is available at:
Keywords: Hispanic Americans
functional annotation
musculoskeletal pain
Case-Control Studies
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Hispanic Americans
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled
Sp4 Transcription Factor
Surveys and Questionnaires
Temporomandibular Joint Disorders
United States
1105 Dentistry
Publication Status: Published
Conference Place: United States
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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