ArticleThe Journal of clinical endocrinology and metabolism2025
Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- IL-34 as a Novel Mediator Linking Vitamin D Deficiency with Osteoporosis and Knee Osteoarthritis.International journal of molecular sciences · 2025Article
- Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density.The Journal of clinical endocrinology and metabolism · 2025Article
- Comment on 'A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses' by Ren et al.-The Authors' Reply.Journal of cachexia, sarcopenia and muscle · 2025Article
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Authors and funding
19 authors.
Funding
Abstract
contextDespite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD).
objectiveWe aimed to investigate the shared genetic architecture and causal relationship between serum 25OHD and BMD, providing insights into their underlying biological mechanisms.
methodsLeveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417 580) and estimated heel BMD (eBMD, N = 426 824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design.
resultsDespite a lack of global genetic correlation (rg=-0.001; P = .95), a statistically significant local signal was discovered at 5p11-5q11.9. Two-sample mendelian randomization (MR) indicated no causal association in the overall population (β=.003, 95% CI, -0.04 to 0.03; P = .93), while positive causal effects were observed in males (β=.005, 95% CI, 0.00 to 0.01; P = .03) and older individuals (β=.009, 95% CI, 0.00∼0.02; P = .01) according to one-sample MR. A total of 49 pleiotropic single-nucleotide variations (SNVs), with 4 novel SNVs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exocrine/endocrine, and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes.
conclusionThis study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among men and individuals older than 65 years. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.
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