| Title: | Clinical implications of bone marrow adiposity identified by phenome-wide association and Mendelian randomization in the UK Biobank |
| Journal: | Nature Communications |
| Published: | 23 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40987763/ |
| DOI: | https://doi.org/10.1038/s41467-025-63395-1 |
| URL: | https://www.nature.com/articles/s41467-025-63395-1.pdf |
Publication 19435
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Abstract
Bone marrow adiposity changes in diverse diseases, but the full scope of these, and whether they are directly influenced by marrow adiposity, remains unknown. To address this, we previously measured the bone marrow fat fraction of the femoral head, total hip, femoral diaphysis, and spine of over 48,000 UK Biobank participants. Here, we first use these data for PheWAS to identify diseases associated with marrow adiposity at each site. This reveals associations with 47 incident diseases across 12 disease categories, including osteoporosis, fracture, type 2 diabetes, cardiovascular diseases, cancers, and other conditions that burden public health worldwide. Intriguingly, type 2 diabetes associates positively with spine bone marrow adiposity but negatively with marrow adiposity at femoral sites. We then establish PRSs based on bone-marrow-fat-fraction-associated SNPs and use PRS-PheWAS and Mendelian randomization to explore causal associations between marrow adiposity and disease. PRS-PheWAS reveals that genetic predisposition to increased marrow adiposity is positively associated with osteoporosis and fractures. Mendelian randomization further suggests that increased marrow adiposity at the diaphysis and total hip is causally associated with osteoporosis. Our findings substantially advance understanding of how marrow adiposity impacts human health and highlight its potential as a biomarker and/or therapeutic target for diverse human diseases.</p>
17 Keywords
- Adiposity
- Aged
- Biological Specimen Banks
- Bone Marrow
- Diabetes Mellitus, Type 2
- Female
- Fractures, Bone
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Osteoporosis
- Polymorphism, Single Nucleotide
- UK Biobank
- United Kingdom
17 Authors
- Wei Xu
- Ines Mesa-Eguiagaray
- David M. Morris
- Chengjia Wang
- Calum D. Gray
- Samuel Sjöström
- Giorgos Papanastasiou
- Sammy Badr
- Julien Paccou
- Lijuan Wang
- Xue Li
- Paul R. H. J. Timmers
- Maria Timofeeva
- Scott IK Semple
- Tom MacGillivray
- Evropi Theodoratou
- William P. Cawthorn
1 Application
| Application ID | Title |
|---|---|
| 48697 | OPTIMAT: Population-level Imaging, genomic and phenotypic analyses to determine how bone marrow adiposity impacts human health |
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