Developmental dysplasia of the hip (DDH) is a polygenetic disease that increases the risk of hip osteoarthritis. A new multi-ethnic study has found that variations in three genes related to collagen and bone formation are associated with DDH. Other downstream genes are also associated with hip osteoarthritis. These findings point to possible mechanisms behind DDH and potential targets for new treatments for hip osteoarthritis.
Developmental dysplasia of the hip (DDH) is a disorder of the hip joint that affects posture and movement. Symptoms of DDH can appear as early as a few weeks after birth and can range in severity from mild to complete hip dislocation. People with DDH are at increased risk of developing hip osteoarthritis (hip OA) due to abnormal wear and tear on the hip joint.
Family history plays a big role in DDH. People who have a parent or sibling with DDH are 12 times more likely to have DDH. Could genetic factors associated with DDH influence the progression of hip OA? A research team led by Dr. Ryosuke Yamaguchi of Kyushu University and Dr. Chikashi Terao of the RIKEN Center for Integrative Medical Sciences set out to answer this question.
Dr. Yamaguchi and Dr. Terao led a multinational, multicenter, genome-wide association study (GWAS) to identify genetic variations common to DDH and hip OA but absent in healthy individuals. Their study included tissue samples from Japan and the United Kingdom. The researchers first conducted separate GWAS for hip dysplasia with and without dislocation, and then conducted a summary meta-analysis on an additional 350,000 samples from across Europe. This is the largest GWAS on DDH and hip OA to date. Their findings were published online in the journal 31 March 2026. bone research.
Researchers found that mutations at three genetic loci are common to both DDH and hip OA. these are COL11A2codes for one of the protein chains that make collagen. CALN1 Encodes a calcium-binding protein. and TRPM7regulates magnesium and calcium ion levels and affects bone regeneration. Interestingly, COL11A2 and CALN1 Variations appear to have different effects on hip dysplasia and hip dislocation. ”A total of nine genetic loci were identified for DDH and its subtypes, and hip dysplasia without dislocation showed different genetic signals than hip dislocation.” added Dr. Yamaguchi.Taken together, these suggest that a polygenic structure is primarily shared between the two subsets of DDH, but that there are genetic differences at some specific 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 be involved in the abnormal appearance of bone tissue within the joint that indicates the progression of hip OA. Additionally, changes in regions of non-coding DNA were also found to be similar in DDH and hip OA, suggesting that changes in the regulation of functional genes by non-coding DNA may be common to both diseases.
DDH is known to increase the risk of hip OA, and recent studies have shown that approximately 70% of Japanese hip OA patients have some form of DDH. ”This study identified susceptibility loci for DDH and hip OA and candidate responsible genes at the loci.” added Dr. Terao.These findings highlight the need for future DDH-specific multi-omics studies that integrate 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 disease.”
Understanding the genetic basis and drivers of DDH will enable the development of specific and targeted treatments for each subtype of DDH, potentially slowing the progression of hip OA and significantly improving patients’ quality of life.
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Reference magazines:
Yoshino S. Others. (2026) Genetic study identifies novel genes in developmental dysplasia of the hip. Bone research. DOI: 10.1038/s41413-026-00514-8. https://www.nature.com/articles/s41413-026-00514-8
