Comparison between UK Biobank and Shanghai Changfeng suggests distinct hip morphology may contribute to ethnic differences in the prevalence of hip osteoarthritis

Zheng, Jiayi; Frysz, Monika; Faber, Benjamin G.; Lin, Huandong; Ebsim, Raja; Ge, Jieyu; Yong, Yanling; Saunders, Fiona R.; Gregory, Jennifer S.; Aspden, Richard M.; Harvey, Nicholas C.; Jiang, Bing-Hua; Cootes, Timothy; Lindner, Claudia; Gao, Xin; Wang, Sijia; Tobias, Jonathan H.

doi:10.1016/j.joca.2023.10.006

Cited by 5 publications

(3 citation statements)

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“…That said, it is known that variations in hip shape exist between European and East Asian populations (17). Future work, harnessing the resources of these large population studies with genetic data, could explore the incorporation of polygenic risk scores to assess whether their inclusion can enhance the performance of disease prediction models (39).…”

Section: Discussionmentioning

confidence: 99%

“…In both UKB and SC (cohort details in Supplementary Methods), eighty-five landmark points were placed automatically around the proximal left femur to outline the femoral head, metaphysis, lesser and greater trochanters, and superior acetabulum. This automatic process has been described previously (15,17). A statistical shape model was built from points fitted to all available images in UKB.…”

Section: Hip Shape Measurementmentioning

confidence: 99%

“…In this study, we aimed to conduct a GWAS meta-analysis of the top 10 HSMs, in UKB and Shanghai Changfeng (SC) cohorts, where these HSM have been derived using our novel automated point placement method (17). Single nucleotide polymorphisms (SNPs) associated with hip shape were then used as genetic instruments in MR analyses evaluating whether hip shape is causally related to either hip osteoarthritis or hip fracture.…”

Section: Introductionmentioning

confidence: 99%

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Hip shape shows a causal effect on hip fracture but not hip osteoarthritis: findings from a GWAS meta-analysis and causal analyses

Faber,

Frysz,

Zheng

et al. 2024

Preprint

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Objectives Hip shape is thought to be an important causal risk factor for hip osteoarthritis and fracture. We aimed to identify genetic determinants of hip shape and use these to assess causal relationships with hip osteoarthritis. Methods Statistical hip shape modelling was used to derive 10 hip shape modes (HSMs) from DXA images in UK Biobank and Shanghai Changfeng cohorts (ntotal=43,485). Genome-wide association study meta-analyses were conducted for each HSM. Two-sample Mendelian randomisation (MR) was used to estimate causal effects between HSM and hip osteoarthritis using hip fracture as a positive control. Results Analysis of the first 10 HSMs identified 290 independent association signals (P<5×10-8). Hip shape SNPs were also associated (P<1.7×10-4) with hip osteoarthritis (n=29) and hip fracture (n=4). Fine mapping implicated SMAD3 and PLEC as candidate genes that may be involved in the development of hip shape and hip osteoarthritis. MR analyses suggested there was no causal effect between any HSM and hip osteoarthritis, however there was evidence that HSM2 (higher neck-shaft angle) and HSM4 (wider femoral neck) have a causal effect on hip fracture (ORIVW1.27 [95% CI 1.12-1.44], P=1.79×10-4and ORIVW0.74 [0.65-0.84], P=7.60×10-6respectively) Conclusions We report the largest hip shape GWAS meta-analysis that identifies hundreds of novel loci, some of which are also associated with hip osteoarthritis and hip fracture. MR analyses suggest hip shape may not cause hip osteoarthritis but is implicated in hip fractures. Consequently, interventions aimed at modifying hip shape in older adults to prevent hip osteoarthritis may prove ineffective.

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Section: Discussionmentioning

confidence: 99%

Section: Hip Shape Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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