Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women

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Abstract
Objective: To more finely linkage‐map primary osteoarthritis (OA) susceptibility loci on chromosomes 4 and 16.Methods: Two hundred eighteen families, each with 2 or more women concordant for primary OA (ascertained by total hip replacement [THR] or total knee replacement), were genotyped using highly polymorphic microsatellite markers from chromosomes 4 and 16, at an average density of 1 marker every 4 cM. Two‐point and multipoint linkage analyses were performed for all 218 families and for the 146 families from the 218 that included women concordant for THR (female‐THR families).Results: A single region of linkage was identified on chromosome 4q, with a maximum multipoint logarithm of odds (LOD) score (MLS) of 3.1 in the 146 female‐THR families. This locus was centered 79 cM from the 4p telomere and had a 1‐LOD support interval of 4 cM. Two regions of linkage were identified on chromosome 16, the first on 16p with an MLS of 1.7 in the female‐THR families and the second on 16q with an MLS of 1.9 in all 218 families. The first locus was centered 46 cM and the second 89 cM from the p‐telomere. The 1‐LOD support intervals were 12 cM and 10 cM, respectively.Conclusion: Finer linkage mapping using a high density of microsatellite markers has narrowed female OA susceptibility loci on chromosomes 4 and 16. The regions have been narrowed sufficiently for association analysis.