Fig. 5: Diverse effects of genetic variants on Aβ levels and cognitive function.

a Bar plots illustrating the incremental r² for clinical diagnosis and Aβ in comparison to previously reported variants (Bellenguez et al.), previously unreported identified variants, RVs, and SVs (K-ROAD). b Stacked bar plot depicting the distribution of samples categorized as APOE ε4 carriers, PRS top 20% group, RNV, or SV carriers based on clinical diagnosis status and Aβ positivity. Cases possessing two or more genetic factors were categorized into groups according to the number of factors present: two, three, or four factors. c Violin plots illustrating the distribution of Aβ, K-MMSE, CDR-SB, verbal memory, and visual memory scores in each group. Box plots indicate the median (center line) and interquartile range (bounds of the box). d Forest plot comparing the differences in Aβ positivity and cognitive function markers between groups carrying only APOE ε4 (n = 437) and those with high PRS, RNV, or SV along with APOE ε4. PRS calculations were based on variants identified in PRS calculations were based on variants identified in a prior European GWAS (Bellenguez et al.) or variants from the current study (K-ROAD). e Forest plot comparing differences in Aβ positivity within each PRS quintile for carriers and non-carriers of APOE ε4, RNV, and SV. Two-sided logistic or linear regression was performed to assess statistical significance in the violin and forest plots, adjusting for age, sex, batch, education, and the top 10 principal components of genetic ancestry, followed by FDR correction for multiple comparisons. FDR-adjusted P-values are presented. Error bars represent 95% confidence intervals. n indicates the number of independent participants. Source data are provided as a Source Data file. Aβ, Amyloid beta; K-ROAD, Korea Registries to Overcome and Accelerate Dementia Research; RV, rare variants; SV, structural variants; RNV, rare noncoding variant; PRS, polygenic risk score; DAT, dementia of Alzheimer’s type; MCI, mild cognitive impairment; CU, cognitively unimpaired; K-MMSE, Korean Mini-Mental State Examination; CDRSB, Clinical Dementia Rating Sum of Boxes.