Table 1.
Prioritizing genes and DNA methylation involved in potentially causal pathways linking genetic variants with Alzheimer’s dementia in brain.
| CHR | CpG | CpG_Gene | mRNA | mRNA_Gene | P_SMR_CpG_mRNA | P_SMR_CpG_AD | P_SMR_mRNA_AD |
|---|---|---|---|---|---|---|---|
| 1 | cg05656486 | NDUFS2 | ENSG00000158864 | NDUFS2 | 3.35 × 10−07 | 2.06 × 10−06 | 4.17 × 10−06 |
| 1 | cg08850169 | NDUFS2 | ENSG00000158864 | NDUFS2 | 1.15 × 10−06 | 5.28 × 10−06 | 4.17 × 10−06 |
| 1 | cg16673712 | UFC1 | ENSG00000158864 | NDUFS2 | 5.79 × 10−07 | 7.21 × 10−05 | 4.17 × 10−06 |
| 1 | cg23274951 | NDUFS2 | ENSG00000158864 | NDUFS2 | 7.73 × 10−07 | 3.89 × 10−06 | 4.17 × 10−06 |
| 1 | cg24049880 | NDUFS2 | ENSG00000158864 | NDUFS2 | 1.87 × 10−07 | 1.33 × 10−06 | 4.17 × 10−06 |
| 7 | cg13210467 | STAG3 | ENSG00000066923 | STAG3 | 5.54 × 10−06 | 3.11 × 10−06 | 1.17 × 10−05 |
| 7 | cg22906224 | STAG3 | ENSG00000066923 | STAG3 | 4.23 × 10−07 | 9.58 × 10−07 | 1.17 × 10−05 |
| 11 | cg03887787 | CTSW | ENSG00000172500 | FIBP | 1.25 × 10−14 | 1.67 × 10−05 | 1.91 × 10−05 |
| 11 | cg19792802 | CTSW | ENSG00000172500 | FIBP | 1.07 × 10−22 | 1.36 × 10−05 | 1.91 × 10−05 |
| 16 | cg02220965 | MYST1 | ENSG00000103510 | KAT8 | 3.76 × 10−19 | 1.78 × 10−05 | 1.28 × 10−05 |
| 16 | cg04275947 | PRSS8 | ENSG00000103510 | KAT8 | 1.09 × 10−07 | 4.88 × 10−05 | 1.28 × 10−05 |
| 16 | cg07078430 | PRSS36 | ENSG00000103510 | KAT8 | 1.83 × 10−07 | 8.74 × 10−06 | 1.28 × 10−05 |
| 16 | cg04275947 | PRSS8 | ENSG00000103549 | RNF40 | 1.58 × 10−05 | 4.88 × 10−05 | 1.27 × 10−04 |
| 16 | cg07078430 | PRSS36 | ENSG00000103549 | RNF40 | 6.64 × 10−04 | 8.74 × 10−06 | 1.27 × 10−04 |
| 16 | cg04275947 | PRSS8 | ENSG00000178226 | PRSS36 | 3.37 × 10−06 | 4.88 × 10−05 | 4.55 × 10−06 |
| 16 | cg07078430 | PRSS36 | ENSG00000178226 | PRSS36 | 2.94 × 10−09 | 8.74 × 10−06 | 4.55 × 10−06 |
| 16 | cg02220965 | MYST1 | ENSG00000196118 | C16orf93 | 5.03 × 10−06 | 1.78 × 10−05 | 1.2 × 10−04 |
| 16 | cg04275947 | PRSS8 | ENSG00000196118 | C16orf93 | 7.13 × 10−06 | 4.88 × 10−05 | 1.2 × 10−04 |
| 17 | cg03433048 | CHRNE | ENSG00000167840 | ZNF232 | 2.24 × 10−06 | 5.03 × 10−05 | 7.65 × 10−06 |
| 17 | cg20814095 | CHRNE | ENSG00000167840 | ZNF232 | 4.92 × 10−06 | 5.07 × 10−05 | 7.65 × 10−06 |
| 17 | cg03433048 | CHRNE | ENSG00000234327 | AC012146.7 | 8.92 × 10−08 | 5.03 × 10−05 | 9.77 × 10−07 |
| 17 | cg20814095 | CHRNE | ENSG00000234327 | AC012146.7 | 2.58 × 10−06 | 5.07 × 10−05 | 9.77 × 10−07 |
We included results that passed correction for multiple testing (FDR P < 0.05) and the HEIDI test (P > 0.01).
CHR means chromosome, P_SMR_CpG_mRNA is the P value in the SMR analysis using mQTL data and eQTL data, P_SMR_CpG_AD is the P value in the SMR analysis using mQTL data and GWAS summary data for Alzheimer’s dementia, and P_SMR_ mRNA_AD is the P value in the SMR analysis using eQTL data and GWAS summary data for Alzheimer’s dementia.
AD, Alzheimer dementia; FDR, false discovery rate; HEIDI, heterogeneity in dependent instruments; SMR, summary data-based Mendelian randomization; eQTL, gene expression quantitative trait loci; mQTL, DNA methylation quantitative trait loci.