This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In order to understand to what extent genetic differences and mode of inheritance influence the expression of spondyloarthritis (SpA), we will develop and validate a patient response instrument to identify the spectrum of SpA phenotypes among affected first degree relatives (FDRs) of probands with AS. We will also try to define the specific major histocompatability complex (MHC) genetic architecture of the heterogeneity of SpA phenotypes in the FDRs of probands with AS by traditional genetic analysis methods and novel designs using a systems biology approach. Both probands and FDRs are not required to come in for their first visit and can complete the instrument via mail. Approximately 125 FDRs will be asked to come to the study site for a second visit (100 who endorsed SpA symptoms and 25 who did not) for blood draw, review of their medical records, and physical examination. FDRs will also have radiographs performed only if, upon review of their medical records and physical examination, their symptoms are suspect for SpA.
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