| Title: | A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses |
| Journal: | Osteoarthritis and Cartilage |
| Published: | 6 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36889626/ |
| DOI: | https://doi.org/10.1016/j.joca.2023.02.073 |
Publication 11175
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Abstract
OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites.</p>
METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner.</p>
RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee.</p>
CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.</p>
22 Authors
- L Zhang
- W Zhang
- X Wu
- H Cui
- P Yan
- C Yang
- X Zhao
- J Xiao
- C Xiao
- M Tang
- Y Wang
- L Chen
- Y Liu
- Y Zou
- L Zhang
- Y Yang
- Y Yao
- J Li
- Z Liu
- C Yang
- B Zhang
- X Jiang
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