Composite model combining polygenic risk score, rare variant data, and methylation risk score improved correlation with plasma LDL-C levels to r=0.272 compared to PRS plus rare variants alone with r=0.263 in Japanese adults with high LDL-C or CAD.
Observational (n=775)
Yes
Does a combined genetic (PRS and rare variants) and epigenetic (MRS) risk model improve the prediction of plasma lipid levels compared to genetic risk alone in Japanese adults?
Combining polygenic risk scores, rare variant analysis, and DNA methylation profiling significantly improves the prediction of plasma LDL-C levels compared to genetic risk scores alone.
Effect estimate: r = 0.272 for composite model with PRS, rare variants, and MRS LDL-C
Absolute Event Rate: 0.272% vs 0.263%
p-value: p=3.7×10^-12
Our results provide a proof-of-concept that assesses the relative contribution of genetic predisposition and DNA methylation levels, which may help individuals refine their dyslipidemia treatment.
Takeuchi et al. (2026) conducted an observational in Adult Japanese patients including high LDL-C subjects without coronary artery disease and subjects with coronary artery disease (n=775). Composite genetic risk model incorporating polygenic risk score (PRS) for LDL-C, rare variant genetic risk, and methylation risk score (MRS) vs. Models using PRS alone or PRS plus rare variants without MRS was evaluated on Correlation between predicted and measured LDL-C plasma levels (r = 0.272 for composite model with PRS, rare variants, and MRS LDL-C, p=3.7×10^-12). Composite model combining polygenic risk score, rare variant data, and methylation risk score improved correlation with plasma LDL-C levels to r=0.272 compared to PRS plus rare variants alone with r=0.263 in Japanese adults with high LDL-C or CAD.