Summary of Findings from the OPPERA Baseline Case-Control Study: Implications and Future Directions

Abstract

The articles in this Compendium present first findings from the baseline case-control study of the OPPERA Program, a series of studies designed to identify risk factors for onset and persistence of painful Temporomandibular Disorders (TMD). This first series of manuscripts represents precursors to the ultimate goal of the OPPERA Program study, which is to build and then test a multivariable model designed to identify causal determinants of new onset TMD, as well as its chronicity. Embedded in OPPERA’s baseline phase was a case-control study of chronic TMD, which collected extensive phenotypic and genotypic data from individuals with examiner-classified TMD arthralgia, myalgia, or both (“TMD cases”) and people who were found not to have TMD when examined (“controls”). The heuristic model guiding the OPPERA study hypothesizes that development and clinical manifestation of TMD is driven by two global intermediate phenotypes, psychological distress and pain amplification, which in turn are influenced by both genetic factors and environmental exposures.6 To address the model’s hypotheses, phenotypic data were collected across multiple domains, including socio-demographic, clinical, psychosocial, pain sensitivity, and autonomic function. Genetic data were also obtained in order to identify potential biological pathways underlying these intermediate phenotypes and thereby contributing causally to the development of TMD. After an overview, which provides the background and conceptual foundation for OPPERA, each of the subsequent articles reports associations between a particular phenotypic domain and TMD while the final article presents genetic associations with TMD. Rather than attempting a comprehensive analysis of this rich and complex dataset, the purpose of this first series of publications is to present the OPPERA data collection methods and to provide descriptive findings from this baseline phase. Future manuscripts will directly address the primary and secondary hypotheses of the OPPERA program. Consistent with the epidemiological approach to case-control studies, this series of papers reports odds ratios as measures of the degree of association between putative risk factors and TMD.10 For the numerous risk factors measured as continuous variables, such as psychological scales, standardized odds ratios were computed, representing the change in odds of TMD associated with an increase of one standard deviation of the continuous variable. The term “risk factor” is used broadly to represent variables (both etiologic events and characteristics) present prior to onset of TMD as well as those that occur during or after onset to exacerbate the symptoms of TMD. The variables of interest range from external causes of tissue damage to psychological and physiological processes affecting pain perception. Also included are commonly-occurring genetic variants that regulate biological pathways influencing those processes. Thus, across all manuscripts, the term “risk factor” conveys association and is not intended to imply causal influence or even temporal sequence. Below, we briefly summarize and integrate the major findings from each article and discuss future plans to elucidate factors underlying the development of TMD within the OPPERA Program.