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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
Author(s) -
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.
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40584
Subject(s) - acetabulum , femoral head , medicine , population , osteoarthritis , orthodontics , anatomy , pathology , alternative medicine , environmental health
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 KLHDC 5/ PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model ( P = 1 × 10 −5 ). The DOT 1L rs12982744 OA risk allele was associated with reduced superior joint space in the subregional shape model ( P = 2 × 10 −3 ). The COL 11A1 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 COL 11A1 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 KLHDC 5/ PTHLH and COL 11A1 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.