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

TitleGWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2017
AuthorsSanders 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
JournalJ Dent Res
Volume96
Issue3
Pagination277-284
Date Published2017 03
ISSN1544-0591
KeywordsBrazil, Case-Control Studies, Dystrophin, Female, Finland, Genetic Loci, Genetic Predisposition to Disease, genome-wide association study, Genotype, Germany, Hispanic Americans, Humans, Male, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Receptors, G-Protein-Coupled, Sarcoglycans, Sp4 Transcription Factor, Surveys and Questionnaires, Temporomandibular Joint Disorders, United States
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) 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) 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) 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) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10) 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.

DOI10.1177/0022034516686562
Alternate JournalJ Dent Res
PubMed ID28081371
PubMed Central IDPMC5298397
Grant ListR01 HL087679 / HL / NHLBI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
HHSN268201200008C / HL / NHLBI NIH HHS / United States
P30 AG028740 / AG / NIA NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
U01 DE017018 / DE / NIDCR NIH HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
HHSN268201200008I / HL / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
R01 MH063706 / MH / NIMH NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
MS#: 
0380
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Manuscript Status: 
Published