Table 1:
CpGs mapping to FTLD-associated loci showing differential methylation in FTLD cohorts and their subtypes compared to controls (absolute delta-beta ≥ 5% and nominal p< 0.05).
| FTLD1m: FTLD vs CTRL | |||||||
|---|---|---|---|---|---|---|---|
| Gene | CpG | Chr | Position | Feature | CGI | Delta-beta | p-value |
| MAPT | cg01934064 | 17 | 44064242 | Body | shelf | −0.14 | 0.024 |
| MAPT | cg15323584 | 17 | 44022846 | 5’UTR | shelf | 0.11 | 0.009 |
| MAPT | cg17569492 | 17 | 44026659 | 5’UTR | island | 0.09 | 0.019 |
| MAPT | cg12727978 | 17 | 44075500 | Body | opensea | 0.08 | 0.009 |
| TREM2 | cg02828883 | 6 | 41131823 | TSS1500 | opensea | 0.08 | 0.005 |
| TIA1 | cg14434028 | 2 | 70452453 | Body | opensea | 0.08 | 0.036 |
| TIA1 | cg13119546 | 2 | 70444039 | Body | opensea | 0.05 | 0.041 |
| RUNX2 | cg16181497 | 6 | 45409732 | Body | opensea | −0.07 | 0.042 |
| RUNX2 | cg12755953 | 6 | 45430813 | Body | opensea | 0.06 | 0.039 |
| RUNX2 | cg04110902 | 6 | 45500999 | Body | opensea | 0.05 | 0.038 |
| GRN | cg06800040 | 17 | 42427647 | Body | shelf | 0.07 | 0.022 |
| FTLD1m by subtype: TDP Type A C9orf72 vs CTRL | |||||||
| MAPT | cg15323584 | 17 | 44022846 | 5’UTR | shelf | 0.17 | 0.002 |
| MAPT | cg12727978 | 17 | 44075500 | Body | opensea | 0.15 | 0.001 |
| MAPT | cg17569492 | 17 | 44026659 | 5’UTR | island | 0.1 | 0.032 |
| MAPT | cg19276540 | 17 | 44060353 | Body | island | 0.08 | 0.035 |
| RUNX2 | cg12041069 | 6 | 45341222 | Body | shelf | 0.15 | 0.04 |
| RUNX2 | cg17636752 | 6 | 45391973 | Body | shore | 0.09 | 0.036 |
| RUNX2 | cg12755953 | 6 | 45430813 | Body | opensea | 0.08 | 0.026 |
| TIA1 | cg14434028 | 2 | 70452453 | Body | opensea | 0.13 | 0.011 |
| TIA1 | cg13119546 | 2 | 70444039 | Body | opensea | 0.06 | 0.047 |
| TIA1 | cg15836561 | 2 | 70442511 | ExonBnd | opensea | 0.06 | 0.028 |
| TBK1 | cg23175599 | 12 | 64848891 | 5’UTR | shelf | 0.1 | 0.026 |
| TREM2 | cg02828883 | 6 | 41131823 | TSS1500 | opensea | 0.09 | 0.017 |
| CCNF | cg26647200 | 16 | 2482775 | Body | shelf | 0.09 | 0.022 |
| GRN | cg06800040 | 17 | 42427647 | Body | shelf | 0.08 | 0.031 |
| GRN | cg12837296 | 17 | 42426483 | 5’UTR | opensea | 0.07 | 0.033 |
| GRN | cg23570245 | 17 | 42426011 | 5’UTR | opensea | 0.06 | 0.048 |
| GRN | cg08491241 | 17 | 42421960 | TSS1500 | opensea | 0.06 | 0.05 |
| SQSTM1 | cg05578452 | 5 | 179255653 | Body | opensea | 0.07 | 0.005 |
| SQSTM1 | cg09046399 | 5 | 179264098 | 3’UTR | opensea | 0.06 | 0.025 |
| FTLD1m by subtype: TDP Type C vs CTRL | |||||||
| MAPT | cg01934064 | 17 | 44064242 | Body | shelf | −0.16 | 0.016 |
| MAPT | cg17569492 | 17 | 44026659 | 5’UTR | island | 0.08 | 0.045 |
| MAPT | cg26979107 | 17 | 44061355 | Body | shore | 0.06 | 0.016 |
| MAPT | cg22635938 | 17 | 44039549 | 5’UTR | opensea | −0.06 | 0.012 |
| MAPT | cg01582587 | 17 | 44036817 | 5’UTR | opensea | 0.05 | 0.022 |
| TBK1 | cg09999583 | 12 | 64878162 | Body | opensea | −0.1 | 0.029 |
| TREM2 | cg02828883 | 6 | 41131823 | TSS1500 | opensea | 0.08 | 0.009 |
| TIA1 | cg17674811 | 2 | 70443967 | Body | opensea | −0.06 | 0.032 |
| RUNX2 | cg04110902 | 6 | 45500999 | Body | opensea | 0.06 | 0.023 |
| FTLD2m: FTLD vs CTRL | |||||||
| TBK1 | cg15343732 | 12 | 64862422 | Body | opensea | 0.09 | 0.034 |
| STX6 | cg02925840 | 1 | 180992110 | TSS200 | island | −0.08 | 0.003 |
| MOBP | cg14968361 | 3 | 39543547 | 5’UTR | shore | 0.08 | 0.050 |
| TIA1 | cg20423569 | 2 | 70452935 | Body | opensea | −0.05 | 0.008 |
| FTLD2m by subtype: Tau MAPT vs CTRL | |||||||
| MOBP | cg14968361 | 3 | 39543547 | 5’UTR | shore | 0.1 | 0.042 |
| TREM2 | cg25748868 | 6 | 41131213 | TSS1500 | opensea | 0.09 | 0.025 |
| SQSTM1 | cg17602756 | 5 | 179246001 | 5’UTR | shore | −0.08 | 0.021 |
| STX6 | cg02925840 | 1 | 180992110 | TSS200 | island | −0.07 | 0.037 |
| TIA1 | cg20423569 | 2 | 70452935 | Body | opensea | −0.06 | 0.005 |
| FUS | cg18647183 | 16 | 31201691 | Body | opensea | 0.06 | 0.042 |
| MAPT | cg05533539 | 17 | 44104521 | 3’UTR | opensea | 0.06 | 0.017 |
| FTLD2m by subtype: TDP Type A GRN vs CTRL | |||||||
| RUNX2 | cg18323984 | 6 | 45386802 | Body | shore | 0.09 | 0.018 |
| MOBP | cg24050474 | 3 | 39544326 | Body | shore | 0.09 | 0.046 |
| CCNF | cg02796204 | 16 | 2499223 | Body | opensea | 0.08 | 0.031 |
| STX6 | cg02925840 | 1 | 180992110 | TSS200 | island | −0.08 | 0.015 |
| OPTN | cg16907766 | 10 | 13143470 | 5’UTR | shore | 0.07 | 0.041 |
| APOE | cg21879725 | 19 | 45412647 | 3’UTR | shore | −0.06 | 0.027 |
| GRN | cg10591948 | 17 | 42421375 | TSS1500 | opensea | 0.06 | 0.03 |
| FTLD2m by subtype: TDP Type B C9orf72 vs CTRL | |||||||
| VCP | cg10828210 | 9 | 35072977 | TSS1500 | shore | −0.23 | 0.017 |
| STX6 | cg05301102 | 1 | 180992117 | TSS200 | island | −0.12 | 0.032 |
| STX6 | cg02925840 | 1 | 180992110 | TSS200 | island | −0.09 | 0.001 |
| TBK1 | cg15343732 | 12 | 64862422 | Body | opensea | 0.09 | 0.022 |
| RUNX2 | cg18323984 | 6 | 45386802 | Body | shore | 0.08 | 0.015 |
| GRN | cg01524226 | 17 | 42427606 | Body | shelf | 0.06 | 0.007 |
| GRN | cg10591948 | 17 | 42421375 | TSS1500 | opensea | 0.06 | 0.03 |
| FTLD3m: Tau PSP vs CTRL | |||||||
| STX6 | cg02925840 | 1 | 180992110 | TSS200 | Island | −0.32 | 1.66E-07 |
| MAPT | cg02804087 | 17 | 43972969 | 5’UTR | Island | 0.1 | 0.027 |
| MAPT | cg11489262 | 17 | 43973426 | 5’UTR | Island | 0.08 | 0.016 |
| SOD1 | cg16086310 | 21 | 33031992 | 5’UTR | Island | −0.08 | 0.002 |
| RUNX2 | cg23261343 | 6 | 45413792 | Body | opensea | 0.05 | 0.044 |
CpGs highlighted in bold reached epigenome-wide significance (FDR adjusted p-value ≤ 0.05). FTLD – frontotemporal lobar degeneration; PSP – progressive supranuclear palsy; CTRL – controls; CpG – DNA methylation sites; Chr – chromosome; CGI – CpG Islands and other regions; TSS – transcription start site; TSS200 – 0–200 bases upstream of TSS; TSS1500 – 200–1500 bases upstream of TSS; UTR – untranslated region.