Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Observational and genetic relationships between hip shape and hip osteoarthritis: findings from UK Biobank (#137)

Monika Frysz 1 2 , B G Faber 1 2 , R Ebsim 3 , F R Saunders 4 , J S Gergory 4 , N C Harvey 5 , C Linder 4 , T Cootes 4 , J P Kemp 1 6 7 , J H Tobias 1 5
  1. Musculoskeletal Research Unit, University of Bristol, UK
  2. Medical Research Council Integrative Epidemiology Unit at the University of Bristol, UK
  3. Division of Informatics, Imaging and Data Science, The University of Manchester, UK
  4. Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, UK
  5. Medical Research Council Lifecourse Epidemiology Centre , University of Southampton, UK
  6. Diamantina Institute, University of Queensland, Woolloongabba, Australia
  7. Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia

Background

Hip shape is an important risk factor for hip osteoarthritis (HOA). In the present study, we used statistical shape modelling (SSM) to evaluate observational relationships between hip shape and HOA, and genetic associations with hip shape using UK Biobank (UKB) dual-energy X-ray absorptiometry (DXA) images.

Methods

Statistical shape modelling (SSM) was used to quantify hip shape (BoneFinder, University of Manchester) from DXA images and generate orthogonal modes of variation (hip shape modes (HSMs)). The first ten HSMs were analysed for associations with HOA outcomes (hospital diagnosed HOA, and grade 2 and ≥3 radiographic HOA (rHOA)) using logistic regression and total hip replacement (THR) using Cox proportional hazards regression. Genome-wide association (GWA) analyses were adjusted for age, sex, genotyping chip and 20 ancestry principal components. GCTA-COJO was implemented to identify conditionally independent SNPs at each genome-wide significant HSM-associated locus.

Results

A total of 40,311 individuals were included in observational analyses (mean 63.7 years, 47.8% male), of whom 5.7% had grade 2 rHOA, 1.7% grade ≥3 rHOA, 1.3% hospital diagnosed HOA, and 0.6% underwent THR. Combined results for grade 2 rHOA revealed femoral neck widening, increased acetabular coverage, and enlarged lesser and greater trochanters. In contrast, grade ≥3 rHOA, hospital diagnosed HOA and THR were suggestive of cam morphology and reduced acetabular coverage. Genetic analyses in 38,175 individuals identified a total of 233 conditionally independent signals associated with the first ten HSMs at genome-wide significance (p<5x10-8) which mapped to 201 loci (based on a 1mb sliding window).

Conclusions

Observational relationships between hip shape and HOA differed according to severity. Notably, cam morphology and acetabular dysplasia were features of severe HOA, but unrelated to moderate disease, suggesting possible prognostic utility. Genetic analyses revealed several loci not previously found to associate with hip shape.