GWAS Identifies New Loci for Painful Temporomandibular Disorder.
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.
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https://hdl.handle.net/10161/13496Published Version (Please cite this version)
10.1177/0022034516686562Publication Info
Sanders, AE; Jain, D; Sofer, T; Kerr, KF; Laurie, CC; Shaffer, JR; ... Smith, SB (2017). GWAS Identifies New Loci for Painful Temporomandibular Disorder. J Dent Res. 10.1177/0022034516686562. Retrieved from https://hdl.handle.net/10161/13496.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Luda Diatchenko
Adjunct Professor in the Department of Anesthesiology
Shad Benjamin Smith
Associate Professor of Anesthesiology
Dr. Shad Smith is an assistant professor in the Department of Anesthesiology and holds
a faculty position in the Center for Translational Pain Medicine (CTPM). Dr. Smith
also has an adjunct appointment at the University of North Carolina at Chapel Hill,
as part of the Center for Pain Research and Innovation (CPRI). He earned his bachelor’s
degree in psychology with minors in chemistry and zoology from Brigham Young University,
before mov
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