Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy

Moschny, Nicole; Zindler, Tristan; Jahn, Kirsten; Dorda, Marie; Davenport, Colin F.; Wiehlmann, Lutz; Maier, Hannah B.; Eberle, Franziska; Bleich, Stefan; Neyazi, Alexandra; Frieling, Helge

doi:10.1186/s13148-020-00891-9

Table 2 DNA methylation analysis—results

From: Novel candidate genes for ECT response prediction—a pilot study analyzing the DNA methylome of depressed patients receiving electroconvulsive therapy

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)

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ISSN: 1868-7083

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