Osteoarthritis (OA) susceptibility is a complex genetic trait influenced by a number of genetic and non-genetic factors. OA represents a huge medical and health care problem as some 70% of people over the age of 65 have some form of OA. Unfortunately, many of the important epidemiologic studies which have implicated genetic factors in OA susceptibility were performed before the molecular genetic era and the patient cohorts used in those studies are no longer available for molecular genetic analysis. Consequently, in order to identify genes involved in common OA susceptibility new patient cohorts must be identified and, when appropriate, DNA from those cohorts must be identified for eventual molecular genetic analysis. Additionally, reliable estimates of the risks- to-relatives, general familial aggregation, and the contribution of non- genetic co-factors to OA susceptibility, as well as the delineation of subtypes of OA under different genetic influences, are required for gene mapping and characterization studies. We propose making use of the vast resources within the Case Western Reserve Medical School and affiliated hospitals to identify probands and their family members for studying the genetic basis of OA susceptibility. As the proposed data collection proceeds, we will assess the familial aggregation and putative monogenic segregation of OA genes in an effort to guide future molecular genetic studies. In addition, we will coordinate the proposed data collection and analyses with extant studies on OA at CWRU in an effort to maximize the yield and general usefulness of the proposed studies. Our initial recruitment of probands and study subjects will be broad, with it in mind that sub-types of OA are likely to emerge during the course of our recruitment that will be more amenable to genetic analysis at molecular levels (e.g., linkage analyses for the identification of susceptibility loci).
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