Causal inference study identifying genetic risk factors for chronic and acute periodontitis — published as a Master's thesis at the University of South Florida (2024).
This study uses two-sample Mendelian Randomization (MR) to evaluate whether five modifiable exposures causally influence periodontal disease risk. By using SNPs as genetic instrumental variables, MR sidesteps the confounding and reverse causation problems that plague observational studies.
Exposures tested:
- Smoking status
- Maternal smoking after birth
- Plasminogen levels
- Creatinine levels
- Absence of psychosocial stress
Outcomes:
- Chronic periodontitis
- Acute periodontitis
| Exposure | Outcome | Direction | Significance |
|---|---|---|---|
| Creatinine levels | Acute periodontitis | Positive ↑ | Significant |
| Maternal smoking | Periodontitis risk | Positive ↑ | Significant |
| Plasminogen levels | Periodontitis risk | Negative ↓ | Significant |
| Smoking status | Chronic periodontitis | Positive ↑ | Borderline |
Highlights:
- Creatinine → acute periodontitis link supports the hypothesis that renal dysfunction amplifies systemic inflammation
- Maternal smoking effect aligns with prenatal nicotine exposure literature
- Plasminogen's negative association diverges from prior pro-inflammatory models — flagged as a priority for follow-up research
All analyses were conducted in R using a two-sample MR framework.
MR methods:
- Inverse Variance Weighted (IVW) — primary estimate
- MR-Egger — tests and corrects for directional pleiotropy
- Weighted Median — robust when up to 50% of IVs are invalid
Instrumental variable selection:
- Genome-wide significance threshold (P < 5×10⁻⁸)
- LD pruning (r² threshold applied)
- Allele harmonization across exposure and outcome GWAS
Sensitivity analyses:
- Leave-one-out analysis
- Cochran's Q heterogeneity test
- Funnel plots and scatter plots for visual diagnostics
Mendelian-Randomization/
└── TwoSampleMR.R # Full MR pipeline: IV selection, harmonization, analysis, sensitivity checks
install.packages(c("TwoSampleMR", "MRInstruments", "tidyverse"))Charles, R. (2024). Unravelling the Impact of Blood Metabolites and Lifestyle Factors on Periodontal Disease Using Mendelian Randomization. Master's Thesis, University of South Florida. https://digitalcommons.usf.edu/etd/10605
Rhea Charles · riocx1997@gmail.com · LinkedIn · GitHub