ArticleFrontiers in medicine2024
Proteome-wide Mendelian randomization provides novel insights into the pathogenesis and druggable targets of osteoporosis.
Article in Frontiers in medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- PHEWAS, TWAS, Mendelian Randomization in Osteoporosis Research: the good, the bad, and the ugly.Current osteoporosis reports · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: With the aging population, the prevalence and impact of osteoporosis are expected to rise, and existing anti-osteoporosis agents have limitations due to adverse events. This study aims to discover novel drug targets for osteoporosis. Methods: The protein data were obtained from the latest proteome-wide association studies (PWAS) including 54, 219 participants. The osteoporosis data were extracted from a GWAS meta-analysis, characterized by heel bone mineral density (HBMD) comprising 426,824 individuals. Mendelian randomization (MR) was the primary approach used to establish genetic causality between specific traits. Summary-data-based MR (SMR), colocalization analysis, heterogeneity test, and external validation were applied to ensure the findings were reliable. The underlying mechanisms behind these causal associations were investigated by additional analyses. Finally, the druggability of the identified proteins was assessed. Results: After Bonferroni correction, a total of 84 proteins were found to have a genetic association with osteoporosis. With strong colocalization evidence, proteins such as ACHE, HS6ST1, LRIG1, and LRRC37A2 were found to negatively influence HBMD, whereas CELSR2, CPE, FN1, FOXO1, and FSHB exhibited a positive association with HBMD. No significant heterogeneity was found. Additionally, CELSR2, FN1, FSHB, HS6ST1, LRIG1, and LRRC37A2 were replicated in the external validation. The effect of FSHB on HBMD was more pronounced in females compared to males. Interestingly, ACHE, LRIG1, FN1, and FOXO1 were observed to partially act on HBMD through BMI. Phewas analysis indicated that CPE and FOXO1 did not have genetic associations with any phenotypes other than osteoporosis. FN1 was highlighted as the most significant protein by protein-protein interaction network analysis. Conclusion: In conclusion, this study offers valuable insights into the role of specific proteins in the development of osteoporosis, and underscores potential therapeutic targets. Future studies should emphasize exploring these causal relationships and elucidating their underlying mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.