A pilot examination of the genome-wide DNA methylation signatures of subjects entering and exiting short-term alcohol dependence treatment programs

Figures & data

Table 1. Clinical and demographic characteristics of study subjects

	Case	Control
n =	33	33
Age	45.5 ± 7.8	46.7 ± 7.8
Ethnicity
White	31	31
African American	2	1
Hispanic	0	1
Gender
Male	25	25
Female	8	8
Days since last drink	4.0 ± 1.8
Average daily drink consumption prior to admission by self report
Past Week	13 ± 13	0
Past Month	13 ± 11	0
Smoking Status
Current Daily	27	1
Positive Cotinine	28	1
Cannabis Use Status
Use in past Year by self report?	11	0
Positive Hydroxy-THC	9	1

Table 2. The Thirty Most Significantly Associated Probes in Case and Control Analyses

Average Beta Values
Probe ID	Gene	Placement	Island Status	Case	Control	T-test	Corrected P value
cg23193759	C10orf35	TSS200	Island	0.128	0.168	4.66E-12	2.26E-06
cg02583484	HNRNPA1	Body	S_Shelf	0.250	0.319	1.42E-11	3.46E-06
cg23779890	GDAP1	TSS200	Island	0.194	0.243	1.30E-10	2.10E-05
cg13415831	SEMA4D*			0.073	0.098	3.18E-10	3.87E-05
cg09935388	GFI1	Body	Island	0.647	0.799	1.35E-09	0.0001
cg01432120	LOC010927881*	Island		0.660	0.720	1.86E-09	0.0002
cg12655542	SCD1*			0.225	0.282	2.18E-09	0.0002
cg11832281	CUGBP2	Body	S Shelf	0.070	0.097	4.20E-09	0.0003
cg06126421	CYP21A2*			0.643	0.750	5.34E-09	0.0003
cg12895631	C11orf75	5′UTR		0.161	0.192	7.07E-09	0.0003
cg25998745	PTK2*			0.588	0.666	8.43E-09	0.0003
cg08352774	TMEM181	Body	S Shelf	0.110	0.149	8.46E-09	0.0003
cg19939077	PPIF	Body	S Shore	0.147	0.184	8.85E-09	0.0003
cg13126206	TNFRSF10B*		S Shelf	0.468	0.521	1.11E-08	0.0004
cg22888484	SNHG11	TSS200	N Shore	0.043	0.056	1.21E-08	0.0004
cg00159243	SELPLG	5′UTR		0.397	0.474	1.76E-08	0.0005
cg24046474	RPL12	Body	N Shore	0.221	0.296	1.89E-08	0.0005
cg00957665	TRIM8	Body	S Shore	0.097	0.125	1.93E-08	0.0005
cg06093152	NENF*			0.572	0.654	2.03E-08	0.0005
cg12126344	TNFRSF8*			0.795	0.835	2.13E-08	0.0005
cg17485265	FAM50B	TSS1500	N Shore	0.677	0.744	2.29E-08	0.0005
cg16854826	ZMIZ1	5′UTR		0.603	0.654	2.42E-08	0.0005
cg23028436	STK38L	TSS200	Island	0.064	0.094	2.89E-08	0.0006
cg00690082	STAT5A	TSS1500	N Shore	0.309	0.376	3.00E-08	0.0006
cg06285727	ATG16L2	TSS1500	N Shore	0.152	0.216	3.68E-08	0.0007
cg09267773	LOC102467146*		N Shore	0.517	0.433	4.00E-08	0.0007
cg21475150	RPL31	TSS1500	Island	0.794	0.849	4.30E-08	0.0007
cg21416692	PHC2	5′UTR		0.742	0.792	4.41E-08	0.0007
cg02348119	TBC1D16	5′UTR		0.598	0.647	4.48E-08	0.0007
cg10691866	TPST1	Body		0.419	0.491	4.55E-08	0.0007

All average methylation values are non-log transformed β-values. Island status refers to the position of the probe relative to the island. Classes include: 1) Island, 2) N (north) shore, 3) S (south) shore, 4) N (north shelf), 5) S (south) shelf and 6) blank denoting that the probe does not map to an island. * denotes that the nearest gene was obtained via use of the UCSC Genome Browser. TSS200 and TSS1500 denote distance (either 200 or 1500 bp) upstream from the transcription start site (TSS).

Table 3. The Top 30 Most Differentially Regulated Gene Ontology Pathways

Genes Log10
GO Category Category Name Total Changed P-Value FDR
GO:0005515	protein binding	6815	286	-7.37	0
GO:0005737	cytoplasm	7845	312	-5.75	0
GO:0008219	cell death	1392	78	-5.69	0
GO:0016265	death	1395	78	-5.66	0
GO:0005829	cytosol	1884	98	-5.63	0
GO:0012501	programmed cell death	1278	72	-5.36	0
GO:0007264	small GTPase mediated signal transduction	566	40	-5.33	0
GO:0043067	regulation of programmed cell death	981	59	-5.3	0
GO:0010941	regulation of cell death	989	59	-5.2	0
GO:0006915	apoptosis	1271	71	-5.16	0
GO:0042981	regulation of apoptosis	974	57	-4.79	0
GO:0023033	signaling pathway	2812	130	-4.73	0
GO:0019899	enzyme binding	671	43	-4.63	0
GO:0048523	negative regulation of cellular process	2069	101	-4.61	0
GO:0002376	immune system process	1256	68	-4.52	0
GO:0023034	intracellular signaling pathway	1707	86	-4.44	0.01
GO:0023052	signaling	3787	164	-4.36	0.01
GO:0065007	biological regulation	7226	283	-4.33	0.01
GO:0048519	negative regulation of biological process	2235	106	-4.31	0.01
GO:0035556	intracellular signal transduction	1454	75	-4.24	0.01
GO:0005622	intracellular	11231	411	-4.22	0.01
GO:0060548	negative regulation of cell death	441	31	-4.21	0.01
GO:0044464	cell part	14663	511	-4.14	0.02
GO:0005623	cell	14664	511	-4.13	0.01
GO:0035466	regulation of signaling pathway	1158	62	-4.02	0.02
GO:0009987	cellular process	11702	424	-3.98	0.02
GO:0043069	negative regulation of cell death	434	30	-3.96	0.02
GO:0007265	Ras protein signal transduction	335	25	-3.91	0.02
GO:0051056	regulation of GTPase signal transduction	339	25	-3.83	0.03
GO:0050794	regulation of cellular process	6319	249	-3.81	0.03

FDR, false discovery rate.