Abstract

Primary osteoarthritis (OA) is a late onset disease that fits most accurately into the oligogenic, multifactorial class of genetic diseases. Twin pair and family risk studies have highlighted a surprisingly large genetic component to OA and have prompted the search for predisposing genes. These searches have taken three forms: (1) parametric linkage analysis of rare families in which OA segregates as a Mendelian trait, (2) model-free linkage analysis of affected sibling pairs, and (3) association analysis of known candidate genes. Within the past year linkage analysis studies have highlighted that chromosomes 2, 4, 6, 7, 11, 16, and the X may each harbor an OA susceptibility gene. Chromosomes 2, 4, and 16 were identified in multiple genome scans and are therefore the most likely to encode susceptibility. Association analysis of candidates suggests that the syntenic genes for type II collagen and the vitamin D receptor (12q12--q13.1) may also encode for OA susceptibility.