Investigation of the Relationship Between Susceptibility Loci for Hip Osteoarthritis and Dual X‐Ray Absorptiometry–Derived Hip Shape in a Population‐Based Cohort of Perimenopausal Women

OBJECTIVE: To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population-based cohort of peri-menopausal women.

METHODS: Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC). The proximal femur and superior acetabulum were outlined, and independent hip shape modes generated. In a sub-regional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA-related SNPs, identified by literature search, and shape modes were analysed in a multivariate canonical correlation analysis.

RESULTS: 3,111 females had genetic and hip shape data (mean 48 years). The KLHDC5-PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P=1x10-5 ). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the sub-regional shape model (P=2x10-3 ). COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the sub-regional shape model (P=5x10-4 ). Regional association plots identified an additional COL11A1 locus in moderate LD with rs4907986, which was more strongly associated with hip shape (rs10047217, P=6x10-6 ). Co-localisation analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC5-PTHLH and COL11A1 loci.

CONCLUSION: Hip OA susceptibility loci were associated with shape in this study suggesting that these loci (and potentially yet to identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development. This article is protected by copyright. All rights reserved.