Table 2.
DNA methylation analysis—results
| Gene | Gene location | CpG | Analysis of variance | SNP | MAF [1.0 = 100%] | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| AQP10 | chr1:154321116…154325325 | chr1:154322027 | Time | F(3, 30) = 17.22 | p < 0.001 | FDR = 0.04 | rs1158005561 | C > T | < 0.01 | T |
| Response | F(1, 10) = 0.47 | p > 0.1 | FDR = 1 | |||||||
| Response × time | F(3, 30) = 1.61 | p > 0.1 | FDR = 0.98 | |||||||
| RNF175 | chr4:153710125…153760235 | chr4:153750274 | Time | F(3, 40) = 3.11 | p < 0.05 | FDR = 0.92 | rs562725996 | G > A | 0.0002 | A |
| Response | F(1, 40) = 46.08 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 40) = 1.92 | p > 0.1 | FDR = 0.98 | |||||||
| RNF213 | chr17:80260866…80395312 | chr17:80353909 | Time | F(3, 40) = 2.32 | p = 0.09 | FDR = 0.93 | rs34269699 | G > A | 0.04014 | A |
| Response | F(1, 40) = 729.15 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 40) = 2.21 | p > 0.1 | FDR = 0.98 | |||||||
| chr17:80353946 | Time | F(3, 40) = 2.28 | p = 0.09 | FDR = 0.93 | rs11656211 | C > T | 0.03934 | T | ||
| Response | F(1, 40) = 538.15 | p < 0.001 | FDR < 0.001 | |||||||
| Response x time | F(3, 40) = 2.71 | p = 0.06 | FDR = 0.98 | |||||||
| chr17:80388468 | Time | F(3, 40) = 2.71 | p = 0.06 | FDR = 0.93 | rs1452340062 | C > T | < 0.01 | T | ||
| Response | F(1, 40) = 415.46 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 40) = 2.87 | p < 0.05 | FDR = 0.98 | |||||||
| chr17:80388469 | Time | F(3, 40) = 1.22 | p > 0.1 | FDR = 0.97 | rs6565682 | G > A | 0.1476 | A | ||
| Response | F(1, 40) = 340.88 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 40) = 1.61 | p > 0.1 | FDR = 0.98 | |||||||
| TBC1D14 | chr4:6909242…6923771 | chr4:6917947 | Time | F(3, 40) = 2.56 | p = 0.07 | FDR = 0.93 | rs7668673 | C > T | 0.2264 | T |
| Response | F(1, 40) = 88.62 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 40) = 1.17 | p > 0.1 | FDR = 0.99 | |||||||
| TMC5 | chr16:19410539…19498140 | chr16:19488803 | Time | F(3, 30) = 0.16 | p > 0.1 | FDR = 0.97 | rs16972066 | C > T | 0.07807 | T |
| Response | F(1, 10) = 9.99 | p < 0.01 | FDR = 0.02 | |||||||
| Response × time | F(3, 30) = 3.31 | p < 0.05 | FDR = 0.98 | |||||||
| TRERF1 | chr6:42225225…42452045 | chr6:42344977 | Time | F(3, 30) = 19.40 | p < 0.001 | FDR = 0.02 | None | None | ||
| Response | F(1, 10) = 1.32 | p > 0.1 | FDR = 1 | |||||||
| Response × time | F(3, 30) = 1.70 | p > 0.1 | FDR = 0.98 | |||||||
| WSCD1 | chr17:6069106…6124427 | chr17:6102035 | Time | F(3, 40) = 0.32 | p > 0.1 | FDR = 0.98 | rs59151763 | G > A | 0.1661 | A |
| Response | F(1, 40) = 51.20 | p < 0.001 | FDR = 0.001 | |||||||
| Response × time | F(3, 40) = 0.56 | p > 0.1 | FDR = 0.99 | |||||||
| Long non-coding RNA | ||||||||||
| AC018685.2 | chr2:2638178…2696285 | chr2:2650193 | Time | F(3, 30) = 2.52 | p = 0.08 | FDR = 0.93 | rs6719244 | C/G/T | 0.07688 | C |
| Response | F(1, 10) = 330.13 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 30) = 2.52 | p = 0.08 | FDR = 0.98 | |||||||
| AC098617.1 | chr2:191846539…192044525 | chr2:191882169 | Time | F(3, 30) = 11.75 | p < 0.001 | FDR = 0.27 | rs1455524094 | G > A | < 0.01 | A |
| Response | F(1, 10) = 22.10 | p < 0.001 | FDR = 1 | |||||||
| Response × time | F(3, 30) = 20.03 | p < 0.001 | FDR = 0.019 | |||||||
| CLCN3P1 | chr9:14921013…15146401 | chr9:15079849 | Time | F(3, 30) = 0.26 | p > 0.1 | FDR = 0.99 | rs10961870 | G > A | 0.2228 | A |
| Response | F(1, 10) = 229.65 | p < 0.001 | FDR < 0.001 | |||||||
| Response × time | F(3, 30) = 0.03 | p > 0.1 | FDR = 1 | |||||||
DNA methylation analysis of 1476812 single CpG sites (repeated ANOVA) revealed five novel protein-coding candidate genes (RNF175, RNF213, TBC1D14, TMC5, WSCD1) and three non-protein coding genes (AC018685.2, AC098617.1, CLCN3P1) to be implicated in ECT response. DNA methylation of two CpGs was found to change significantly during the treatment course (AQP10, TRERF1). All significant CpG sites (but one) do overlap with the loci of a listed single-nucleotide polymorphism (SNP)