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J Dent Res. 2017 Mar;96(3):277-284. doi: 10.1177/0022034516686562. Epub 2017 Jan 12.

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

Author information

1
1 Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
2
2 Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
3
3 Department of Biostatistics, University of Washington, Seattle, WA, USA.
4
4 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
5
5 Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
6
6 Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
7
7 Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
8
8 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
9
9 Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
10
10 Department of Pediatric Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
11
11 Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
12
12 Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.
13
13 Department of Oral Diagnostic Sciences, University at Buffalo, Buffalo, NY, USA.
14
14 Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC, USA.
15
15 Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
16
16 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
17
17 Department of Prosthetic Dentistry, Gerodontology and Biomaterials, University Medicine Greifswald, Greifswald, Germany.
18
18 Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.
19
19 Oral and Maxillofacial Department, Kuopio University Hospital, Kuopio, Finland.
20
20 Research Unit of Oral Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland.
21
21 Oral and Maxillofacial Department, Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
22
22 Oral and Maxillofacial Department, Medical Research Center Oulu, Oulu University Hospital, Finland.
23
23 Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
24
24 Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
25
25 Biocenter Oulu, University of Oulu, Center for Life Course Health Research, University of Oulu, Finland.
26
26 Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
27
27 Department of Prosthesis and Periodontology, Piracicaba Dental Scholl, University of Campinas, Piracicaba, Brazil.
28
28 The Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, Montreal, QC, Canada.
29
29 University of Florida, College of Dentistry, Gainesville, FL, USA.
30
30 Alan Edwards Pain Centre, McGill University, Montreal, QC, Canada.
31
31 Piracicaba Dental School, State University of Campinas, Department of Prosthesis and Periodontology, Brazil.

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.

KEYWORDS:

Hispanic Americans; epidemiology; functional annotation; genetics; musculoskeletal pain; population

PMID:
28081371
PMCID:
PMC5298397
[Available on 2018-03-01]
DOI:
10.1177/0022034516686562
[Indexed for MEDLINE]

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

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