Table 1. . Candidate gene regions examined in previous DNA methylation studies reporting significant associations and the corresponding EPIC probes.
| Candidate gene | Study | Outcome of interest | n | Measurement method | Genomic region (hg19) | Findings in individuals with outcome | Corresponding epic probes associated with dementia/memory deficits | Ref. |
|---|---|---|---|---|---|---|---|---|
| APOE | Liu et al. | Delayed recall | 289 | 450k | chr19:45407868-45412648 | Higher methylation with lower delayed recall score (FDR q <0.1, effect size not shown) |
cg04406254, CpG19:45407945 cg18768621, CpG19:45409440 |
[1] |
| Shao et al. | AD, MCI | 67 | 450k | chr19:45407868-45412599 | Difference between groups in raw analysis (p < 0.5, effect size and direction not shown) |
cg26190885, CpG19:45409005 cg12049787, CpG19:45409080 cg19514613, CpG19:45409713 cg05501958, CpG19:45411873 cg18799241, CpG19:45412599 cg14123992, CpG19:45407868 cg04406254, CpG19:45407945 cg18768621, CpG19:45409440 |
[2] | |
| Karlsson et al. | AD | 447 | 450k | chr19:45407868-45412648 | Higher promoter methylation | cg14123992, CpG19:45407868 cg04406254, CpG19:45407945 cg26190885, CpG19:45409005 |
[3] | |
| Mancera-Paez et al. | MCI | 100 | BS PCR | chr19:45412445-45412605 | Generally higher methylation, in four sig. CpGs. | NA, no sig. EPIC probes | [4] | |
| APP | D'Addario et al. | AD (twins) | 2 | MSP | chr21:27543426-27543579 | Average promoter methylation higher (0.5%, no p-value) | cg27158854, CpG21:27543469 cg10253538, CpG21:27543504 cg08866780, CpG21:27543523 cg00542846, CpG21:27543545 |
[5] |
| Hou et al. | AD | 12 | MSP | chr21:27542923-27543318 | Lower methylation at ten CpGs (p = 0.05, effect size not shown) | NA, no sig. EPIC probes | [6] | |
| BDNF | Chang et al. | AD | 160 | PS | chr11:27743841-27743870 | Average methylation higher (2.05%; p = 0.004) |
NA, no EPIC probes in region | [7] |
| Nagata et al. | AD | 40 | BS PCR | chr11:27722101-27722210 | Average methylation higher (2.99%; p = 0.04) |
NA, no EPIC probes in region | [8] | |
| Xie et al. | aMCI, AD | 458 | PS | Promoter I (P1) chr11:27743543-27743744 Promoter IV (P4) chr11:27723021-27723252 |
Average methylation at four CpGs across both promoters higher at BL (2.99%; p < 0.001) FU (2.49%; p < 0.001) P1: Not sig. at aligned EPIC probe cg16257091, CpG11:27743580 P4: Sig. at aligned EPIC probe cg11241206, CpG11:27723128 at BL: 0.86%; p < 0.001, MCI vs CT FU: 1.76%; p < 0.001, AD vs MCI |
cg11241206, CpG11:27723128 lines up with ‘P4: CpG 6’ | [9] | |
| PIN1 | Arosio et al. | LOAD | 60 | MSP | chr19:9945760-9945910 | Average methylation across region lower (LOAD vs CT) (-7.69%; p = 0.001) |
cg18744802, CpG19:9945810 cg10998950, CpG19:9945815 cg26231243, CpG19:9945826 cg01731038, CpG19:9945838 cg13388992, CpG19:9945906 cg12082325, CpG19:9945909 |
[10] |
| D'Addario et al. | AD (twins) | 2 | MSP | chr19:9945625-9945826 | Average methylation across region lower (-2.0%, no p-value) | cg22728790, CpG19:9945654 cg06539622, CpG19:9945677 cg04699474, CpG19:9945708 cg18744802, CpG19:9945810 cg10998950, CpG19:9945815 cg26231243, CpG19:9945826 |
[5] | |
| Ferri et al. | LOAD, FTD | 317 | PS | chr19:9945616-9945965 | Higher methylation at CpGs (FTD vs CT/AD) (≤0.57%; p ≤ 0.03). |
cg18744802, CpG19:9945810 cg26231243, CpG19:9945826 cg01731038, CpG19:9945838 |
[11] | |
| SNCA | Funahashi et al. | DLB | 40 | PS | chr4:90757391-90757463 | Lower average methylation across region (2.3%; p < 0.001, DLB, vs CT) as well as at seven CpGs | cg14346243, CpG4:90757452 | [12] |
| Yoshino et al. | AD | 100 | PS | chr4:90757391-90757463 | Lower average methylation across region (0.7%; p = 0.027, AD vs CT) as well as at seven CpGs | cg20003494, CpG4:90757398 cg14346243, CpG4:90757452 |
[13] | |
| TOMM40 | Liu et al. | Delayed recall | 289 | 450k | chr19:45393621-45406887 | Increased methylation associated with lower delayed recall score (effect size not shown) | cg22024783, CpG19:45393916 cg12271581, CpG19:45394330 |
[1] |
| Shao et al. | AD, MCI | Pilot: 67 Rep :57 |
450k | chr19:45392813-45407871 | Difference (p < 0.05) between groups pre-adjustment for multiple testing (effect size and direction not shown) | cg22024783, CpG19:45393916 (CT vs MCR, CT vs MCI/AD) cg12271581, CpG19:45394330 (MCI vs AD) cg06632829, CpG19: 45394476 (MCI vs AD) Replication Cohort: (AD vs CT) cg19375044, CpG19:45394343 cg02613937, CpG19: 45395297 cg13447416, CpG19: 45398091 |
[2] |
450K: Illumina 450k array; AD: Alzheimer’s disease; aMCI: Acute mild cognitive impartment; BL: Baseline; BS: Bisulphite; CpG: Cytosine-phosphate-guanine; CT: Controls; DLB: Dementia with Lewy bodies; EPIC: Illumina MethylEPIC array; FDR: False discovery rate; FU: Follow up; FTD: Frontotemporal dementia; LOAD: Late onset Alzheimer’s disease; MCI: Mild cognitive impairment; MSP: Methylation specific PCR; NA: Not available; PS: Pyrosequencing; pval: p-value; Rep: Replication; Sig: Significant.