The inheritance of hip osteoarthritis in Iceland.

Abstract

To assess, in a population-wide study in Iceland, the genetic contribution to hip osteoarthritis (OA) leading to total hip replacement (THR). Information from 2 population-based databases in Iceland was combined: a national registry of all THRs performed between 1972 and 1996, and a genealogy database of all available Icelandic genealogy records for the last 11 centuries. A genetic contribution to THR for OA was assessed by 1) identifying familial clusters of OA patients with THR, 2) applying the minimum founder test (MFT) to estimate the minimum number of ancestors ("founders") that would account for the genealogy of all 2,713 patients with THR for OA, compared with the average number of founders for control lists, 3) calculating an average pairwise kinship coefficient (KC) for the patient list and control lists, and 4) estimating the relative risk (RR) for THR among relatives of OA patients who have undergone the procedure. One thousand matched control lists, each the same size as the patient list, were created using the genealogy database. A large number of familial clusters of patients with THR for OA were identified. The MFT showed that OA patients descended from fewer founders than did subjects in the control groups (P < 0.001). The average pairwise KC among patients with OA was greater than in the control population (P < 0.001). The RR for THR among siblings of OA patients was 3.05 (95% confidence interval 2.52-3.10). This population-based study shows that Icelandic patients with hip replacement for OA are significantly more related to each other than are matched controls drawn from the Icelandic population. These findings support a significant genetic contribution to a common form of OA and encourage the search for genes conferring an increased susceptibility to OA.