We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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.
- Authors
Baird, Denis A.; Paternoster, Lavinia; Gregory, Jennifer S.; Faber, Benjamin G.; Saunders, Fiona R.; Giuraniuc, Claudiu V.; Barr, Rebecca J.; Lawlor, Deborah A.; Aspden, Richard M.; Tobias, Jonathan H.
- Abstract
Objective: To examine relationships between known osteoarthritis (OA) susceptibility loci and hip shape in a population‐based cohort of perimenopausal women in order to investigate whether hip shape contributes to OA development. Methods: Hip shape was measured, using statistical shape modeling, on dual x‐ray absorptiometry scans of the hip 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 were generated. In a subregional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA‐related single‐nucleotide polymorphisms, identified by literature search, and shape modes were analyzed in a multivariate canonical correlation analysis. Results: A total of 3,111 women (mean age 48 years) had genetic and hip shape data. The KLHDC5/PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P = 1 × 10−5). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the subregional shape model (P = 2 × 10−3). The COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the subregional shape model (P = 5 × 10−4). Regional association plots identified an additional COL11A1 locus in moderate linkage disequilibrium with rs4907986, which was more strongly associated with hip shape (rs10047217; P = 3 × 10−6). Colocalization 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‐be‐identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development.
- Subjects
HIP joint diseases diagnosis; OSTEOARTHRITIS diagnosis; OSTEOARTHRITIS; HIP joint diseases; HIP joint; ACETABULUM (Anatomy); ALLELES; DISEASE susceptibility; FEMUR; GENETIC polymorphisms; LONGITUDINAL method; MULTIVARIATE analysis; STATISTICS; PERIMENOPAUSE; DATA analysis; PHOTON absorptiometry; GENETICS; ANATOMY
- Publication
Arthritis & Rheumatology, 2018, Vol 70, Issue 12, p1984
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.40584