Key gene variants tied to developmental dysplasia of the hip and osteoarthritis

Developmental dysplasia of the hip (DDH) is a polygenetic disorder that increases the risk of hip osteoarthritis. A new multiethnic study finds that variations in three genes related to collagen and bone formation are linked to DDH. Other downstream genes are also linked to hip osteoarthritis. These findings point to possible mechanisms behind DDH and potential targets for new therapies against hip osteoarthritis.

Developmental dysplasia of the hip, or DDH, is an abnormality of the hip joint that affects posture and movement. Symptoms of DDH can appear as early as a few weeks after birth and vary in severity from mild to total dislocation of the hip joint. People with DDH are at high risk of developing osteoarthritis of the hip (hip OA) due to abnormal wear on the hip joint.

Family history plays a major role in DDH. People with a parent or sibling with DDH are 12 times more likely to have the disorder. Could genetic factors associated with DDH affect the progression of hip OA? That is the question a research team led by Dr. Ryosuke Yamaguchi from Kyushu University and Dr. Chikashi Terao of the RIKEN Center for Integrative Medical Sciences set out to answer.

Dr. Yamaguchi and Dr. Terao led a multinational, multi-institution, genome-wide association study (GWAS) to identify genetic variations shared between DDH and hip OA but absent in healthy individuals. Their study included tissue samples from Japan and the UK. The researchers first conducted separate GWASs for hip dysplasia with and without dislocation and then conducted a summary meta-analysis on a further 350,000 samples from across Europe, making this the largest GWAS of DDH and hip OA to date. Their findings were made available online on March 31, 2026, in the journal Bone Research.

The researchers found that variations in three genetic loci were common to both DDH and hip OA. These were COL11A2, which codes for one of the protein chains that make collagen; CALN1 which encodes a calcium-binding protein; and TRPM7, which regulates magnesium and calcium ion levels and affects bone regeneration. Interestingly, COL11A2 and CALN1 variations seemed to affect hip dysplasia and hip dislocation differently. "In total, nine loci were identified for DDH and its subtypes, with hip dysplasia without dislocation showing distinct genetic signals from hip dislocation," says Dr. Yamaguchi, adding, "Taken together, these suggest that while polygenic architecture is largely shared between the two subsets of DDH, there are genetic differences in a part of specific genetic loci."

Further analysis showed that several genes affecting bone cell growth and bone remodeling were also associated with DDH. These genes were already known to play a role in the aberrant appearance of bone tissue in joints that marks the progression of hip OA. In addition, variations in regions of non-coding DNA were also found to be similar between DDH and hip OA, suggesting that altered regulation of functional genes by non-coding DNA may be common to both disorders.

DDH is known to increase the risk of hip OA, with recent studies showing that about 70% of Japanese patients with hip OA have some form of DDH. "This study identified susceptibility loci to DDH and hip OA and candidates of responsible genes in the loci," says Dr. Terao, adding, "These findings underscore the need for future DDH-specific multi-omics studies, integrating genetic data with tissue-specific gene expression, chromatin accessibility, and spatial chromatin structure, especially in chondrocytes, to fully elucidate the functional mechanisms underlying this complex disorder."

Understanding the genetic basis and drivers of DDH will enable the development of specific and targeted therapies against each subtype of DDH, slow down the progression of hip OA, and allow patients to have a greatly improved quality of life.