Genome studies and linkage in primary osteoarthritis

Genetic epidemiologic studies have demonstrated that primary OA has a major genetic component that segregates in families in a complex manner. Some of these studies suggest that genetic susceptibility may be more relevant to female OA than to male OA and that genes may have a greater role in OA development and progression at certain joint groups compared with others. These observations are not universal, however, and discrepancies between different studies may simply serve to highlight the complex nature of the transmittance of OA susceptibility. The numerous OA linkage studies that have now been performed have revealed a number of regions of the human genome that are likely to harbor genes predisposing to OA. Several of these regions, particularly those identified in genome-wide scans of ASPs, have relatively low LOD scores; as a result, their reliability must be questioned. Nevertheless, a few of these regions have already been linked in more than one study, and these linkages can be considered as more robust. Such confirmation is a prerequisite to finer linkage mapping, which should narrow the linkage intervals to a point at which comprehensive association analysis of DNA sequence variants can be undertaken.