Separate regulatory variants at GDF5-UQCC1 underlie common knee osteoarthritis risk and developmental dysplasia of the hip

Abstract

Purpose: In Europeans and Asians, a high frequency 130 kb haplotype spanning the GDF5-UQCC1 locus harbors genetic variants that are reproducibly associated with a number of prevalent skeletal diseases, including common hip and knee osteoarthritis (OA) as well as developmental dysplasia of the hip (DDH). However, the causal variants for each disease remain unknown. Here, we used a combination of functional genomic and genetic studies to pinpoint separate single base pair regulatory changes that lead to relevant hip and knee phenotypes when recapitulated in mice.