COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study

Osteoarthr Cartil Open. 2023 Dec 16;6(1):100424. doi: 10.1016/j.ocarto.2023.100424. eCollection 2024 Mar.


Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 ​% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome.

Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) 0.01, R2 0.8 and Hardy-Weinberg equilibrium (HWE) P-value 0.0001. Significance level was set at p ​< ​5 ​× ​10-8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee.

Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (β ​= ​-0.43, SE ​= ​0.07, p ​= ​8.4 ​× ​10-9) and rs6577334 (β ​= ​-0.43, SE ​= ​0.08, p ​= ​8.9 ​× ​10-9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis.

Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.

Keywords: COL11A1; Developmental dysplasia of the hip; Genetic; HUNT; Hip dysplasia.