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A GWAS meta-analysis of alpha angle suggests cam-type morphology may be a specific feature of hip osteoarthritis in older adults.
Arthritis Rheum. 75, 900-909 (2023)
OBJECTIVES: To examine the genetic architecture of cam morphology, using alpha angle (AA) as a proxy measure, we conducted an AA genome wide association study (GWAS), followed by Mendelian randomisation (MR) to evaluate its causal relationship with hip osteoarthritis (HOA). METHODS: Observational analyses examined associations between AA derived from hip DXA scans in UK Biobank (UKB), and radiographic HOA (rHOA) and subsequent total hip replacement (THR). Afterwards, an AA GWAS meta-analysis was performed (n=44,214), using AA previously derived in the Rotterdam Study (RS). Linkage disequilibrium score regression assessed the genetic correlation between AA and HOA. Genetic associations with P<5x10-8 instrumented AA for two-sample MR. RESULTS: DXA-derived AA showed expected associations between AA and rHOA (OR 1.63 [95% CI 1.58-1.67]) and THR (HR 1.45 [1.33-1.59]) in UKB. The heritability of AA was 10% and AA had a moderate genetic correlation with HOA (rg =0.26 [0.10-0.43]). Eight independent genetic signals were associated with AA. Two-sample MR provided weak evidence of causal effects of AA on HOA risk (inverse variance weighted (IVW): OR=1.84 [1.14-2.96], P 0.01). In contrast, genetic predisposition for HOA had stronger evidence of a causal effect on increased AA (IVW: β=0.09 [0.04-0.13], P 4.58 x 10-05 ). CONCLUSIONS: Expected observational associations between AA and related clinical outcomes provided face-validity for the DXA-derived AA measures. Evidence of bidirectional associations between AA and HOA, particularly in the reverse direction, suggests that hip shape modelling secondary to a genetic predisposition to HOA contributes to the well-established relationship between HOA and cam morphology in older adults.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Femoroacetabular Impingement; Acetabular Dysplasia; Deformity
ISSN (print) / ISBN
0004-3591
e-ISSN
1529-0131
Journal
Arthritis & Rheumatology
Quellenangaben
Volume: 75,
Issue: 6,
Pages: 900-909
Publisher
Wiley
Publishing Place
111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)
Grants
Wellcome Trust
National Health and Medical Research Council (Australia)
Sir Henry Dale Fellowship - Royal Society
Sir Henry Dale Fellowship - Wellcome Trust
University Hospital Southampton
NIHR Southampton Biomedical Research Centre, University of Southampton
MRC
Medical Research Council (MRC) clinical research training fellowship
National Health and Medical Research Council (Australia)
Sir Henry Dale Fellowship - Royal Society
Sir Henry Dale Fellowship - Wellcome Trust
University Hospital Southampton
NIHR Southampton Biomedical Research Centre, University of Southampton
MRC
Medical Research Council (MRC) clinical research training fellowship