GWAS Identifies New Loci for Painful Temporomandibular Disorder.
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2017-01-01
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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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Sanders, AE, D Jain, T Sofer, KF Kerr, CC Laurie, JR Shaffer, ML Marazita, LM Kaste, et al. (2017). GWAS Identifies New Loci for Painful Temporomandibular Disorder. J Dent Res. 10.1177/0022034516686562 Retrieved from https://hdl.handle.net/10161/13496.
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Scholars@Duke
Luda Diatchenko
Shad Benjamin Smith
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 moving on to graduate school.
In 2006, he graduated with a doctorate in psychology with an emphasis in behavioral neuroscience. Following his time at McGill, Dr. Smith accepted a post-doctoral fellowship in the CPRI at the UNC School of Dentistry. He received a Ruth L. Kirschstein National Research Service Award in 2008 to study the role of alpha adrenergic mechanisms in chronic orofacial pain. He joined the faculty at UNC as a research assistant professor in 2011. Dr. Smith has also served since 2007 as a research consultant, and since 2010 as the Director of Bioinformatics, for Algynomics, Inc., a Chapel Hill-based biotech firm spun off from research activities within the UNC School of Dentistry.
Dr. Smith joined the faculty at Duke University in 2016, where he continues his work with genetics of pain disorders. The primary focus of his research career has been the search for genetic variation that contributes to greater pain sensitivity and increased risk for chronic pain disease. He has worked for over a decade with genomic techniques, including both quantitative trait locus (QTL) mapping in the mouse and genetic association in human pain cohorts, investigating a number of pain-related diseases and phenotypes. Dr. Smith has published over 40 journal articles and book chapters, and presented his work at several international meetings. His work with projects such as the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study has resulted in a number of novel genes being recognized as genetic risk factors for pain.
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