TY - JOUR
T1 - Facial pain with localized and widespread manifestations
T2 - Separate pathways of vulnerability
AU - Slade, Gary D.
AU - Smith, Shad B.
AU - Zaykin, Dmitri V.
AU - Tchivileva, Inna E.
AU - Gibson, Dustin G.
AU - Yuryev, Anton
AU - Mazo, Ilya
AU - Bair, Eric
AU - Fillingim, Roger
AU - Ohrbach, Richard
AU - Greenspan, Joel
AU - Maixner, William
AU - Diatchenko, Luda
N1 - Funding Information:
This work was supported by the National Institutes of Health, National Institutes of Dental and Cranial Research (grant numbers RO1-DE16558 and UO1-DE017018 to L.D., G.S., W.M.). D.V.Z was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. We are grateful to investigators at OPPERA study sites for their contribution in directing data collection: Dr. Joel Greenspan, University of Maryland, Baltimore, MD; Mr. Charles Knott, Battelle Memorial Inc, Durham, NC.
PY - 2013/11
Y1 - 2013/11
N2 - Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P = 0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P = 0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P = 1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P = 0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P = 1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.
AB - Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P = 0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P = 0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P = 1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P = 0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P = 1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.
KW - Case-control study
KW - Human genetics
KW - Serotonergic receptor
KW - Temporomandibular disorder
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U2 - 10.1016/j.pain.2013.07.009
DO - 10.1016/j.pain.2013.07.009
M3 - Article
C2 - 23867732
AN - SCOPUS:84886236272
SN - 0304-3959
VL - 154
SP - 2335
EP - 2343
JO - Pain
JF - Pain
IS - 11
ER -