Urolithiasis Causes Osteoporosis in Asians: Genetic Evidence from Mendelian Randomization and Pathway Analysis
Authors' conclusion
In conclusion, the study establishes a direct causal link between urolithiasis and OP, independent of environmental factors. Regardless of lifestyle, urolithiasis patients should remain vigilant about the risk of OP and consider regular OP screening. The biological mechanism of urolithiasis combined with OP and related drugs still needs to be further explored.
Study context
- Population
- Japan BioBank: 6638 urolithiasis and 7788 osteoporosis (OP) cases (Asians)Japan BioBank
- Comparison
- Genetically predicted urolithiasis vs OP
- Outcome
- Direct causal relationship between urolithiasis and OP
Methodological detailsgenetic correlation analysis, colocalization, pathway analysis, 10 genetic variants as instrumental variables
- Genetic correlation analysis
- Colocalization
- Pathway analysis
- 10 genetic variants as instrumental variables
Main finding
As reported in the abstract
Genetically predicted urolithiasis → OP
- Positive association between genetically predicted urolithiasis and OP, with significant direct effects persisting after adjusting for OP-associated factors in 4 models
Further findings
Reverse analysis: genetically predicted OP → urolithiasis
- No significant causal effect of genetically predicted OP on urolithiasis
Genetic correlation and colocalization
- No conclusive evidence
Mediation analysis
- Estimated glomerular rate identified as a significant contributor
Co-risk factor analysis
- Cardiovascular elements were common risks for both conditions
Bioanalysis
- Cytokine, metabolic and calcium signaling pathways may bridge urolithiasis and OP; BCAS3, DGKH, TBX2 and TBX2-AS1 potential causal genes
Original publication
Urolithiasis Causes Osteoporosis in Asians: Genetic Evidence from Mendelian Randomization and Pathway Analysis. J Clin Endocrinol Metab. Published 8 July 2024. doi:10.
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