Table 2 Top 10 genes for differentially methylated regions (DMRs) in correlational analyses performed in T0-T1 for the whole cohort and for the female cohort. The Table shows a) the DMRs at T0-T1 and the DMRs analysed with covariates including b) clinical symptoms variations (assessed by delta MADRS) and c) response (reduction greater than 50% in MADRS score at T1). MADRS: Montgomery-Åsberg Depression Rating Scale. Statistically significant genes are highlighted in bold

1

MCF2L

chr13

0.0001

0.0524

Encodes a guanine nucleotide exchange factor that interacts with the guanosine-5'-triphosphate (GTP)-bound Rac1 and plays a role in the Rho/Rac signaling pathways¹

Associates with osteoarthritis [19]

2

SLC25A24

chr1

0.0002

0.0524

Encodes a carrier protein that transports adenosine triphosphate (ATP)-Magnesium exchanging it for phosphate¹

Associated with conduct disorder trait [20]

3

RUNX3

chr1

0.0002

0.0524

Encodes a member of the runt domain-containing family of transcription factors, functions as tumor suppressor gene¹

4

MIR637

chr19

0.0002

0.0524

Micro-RNA gene associated with squamous cell carcinoma, renal cell carcinoma and systemic lupus erythematosus¹

5

FOXK2

chr17

0.0002

0.0524

Involved in the regulation of viral, cellular promoter elements and various types of cancers [21]

6

FAM180B

chr11

0.0002

0.0524

Predicted to be associated with leprosy¹

7

POU6F1

chr12

0.0005

0.0870

Associated with corticotropin-releasing hormone expression regulation, neuroplasticity [22] and lung adenocarcinoma [23]

8

ALS2CL

chr3

0.0005

0.0870

Enables identical protein binding activity, associated with deafness and megalencephalic leukoencephalopathy¹

9

CCRL2

chr3

0.0006

0.0870

Encodes a chemokine receptor like protein, a seven transmembrane protein and related to chemokine receptor 1¹

Involved in immune processes and lung cancer growth [24]

10

TEX55

chr3

0.0008

0.1036

Predicted to be active in nucleus, involved in cryptorchidism¹

1

MIR637

chr19

0.0001

0.0781

Micro-RNA gene associated with squamous cell carcinoma, renal cell carcinoma and systemic lupus erythematosus¹

2

AVPI1

chr10

0.0002

0.0781

Associated with melanoma cells [25] and alcohol dependence [26]

3

RUNX3

chr1

0.0003

0.0781

Encodes a member of the runt domain-containing family of transcription factors, functions as tumor suppressor gene¹

4

MCF2L

chr13

0.0003

0.0781

Associated with different types of cancer [27, 28] and osteoarthritis¹

5

FOXK2

chr17

0.0003

0.0781

Involved in the regulation of viral, cellular promoter elements and various types of cancers [21]

6

FAM124B

chr2

0.0004

0.0781

Associated with anorexia nervosa [29], leukemia and other types of cancer [30]

7

POU6F1

chr12

0.0004

0.0824

Associated with corticotropin-releasing hormone expression regulation, neuroplasticity [22] and lung adenocarcinoma [23]

8

DAZL

chr3

0.0013

0.1330

Associated with schizophrenia [31]

9

IL3

chr5

0.0014

0.1330

Related to inflammatory and immune processes¹

10

SPECC1

chr17

0.0016

0.1330

Associated with some cancer types¹

1

ARFGAP1

chr20

0.0006

0.1283

Encodes a GTPase-activating protein, associated with the Golgi apparatus¹

2

DYNLRB1

chr20

0.0004

0.1283

Encodes a cytoplasmic protein that binds intermediate chain proteins and interacts with transforming growth factor-beta¹

3

DLK1

chr14

0.0001

0.1283

Encodes a transmembrane protein that contains multiple epidermal growth factor repeats functioning as a regulator of cell growth¹

4

SGF29

chr16

0.0005

0.1283

Component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcriptional coactivator complex, related to chromatin organization¹

5

PCDHGA5

chr5

0.0005

0.1283

Member of the protocadherin gamma gene cluster, involved in immunoglobulin-like organization¹

6

CACFD1

chr9

0.0013

0.1371

Predicted to be involved in vesicle-mediated transport¹

7

ECI1

chr16

0.0008

0.1317

Encodes a member of the hydratase/isomerase superfamily, a key mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids¹

8

POT1

chr7

0.0015

0.1371

Member of the telombin family and encodes a nuclear protein involved in telomere maintenance¹

9

LEPROTL1

chr8

0.0010

0.1371

Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway¹

10

ARMC9

chr2

0.0013

0.1371

Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway¹

1

ZFP57

chr6

0.0000

0.0313

Associated with autism spectrum [32] and PTSD symptoms [33]

2

LAT

chr16

0.0001

0.0313

Associated with immune processes¹

3

DLX4

chr17

0.0001

0.0313

Associated with various cancer types¹

4

POT1

chr7

0.0001

0.0313

Member of the telombin family and encodes a nuclear protein involved in telomere maintenance¹

5

POLD4

chr11

0.0002

0.0448

Associated with schizophrenia [34] and various cancer types

6

MCIDAS

chr5

0.0005

0.0844

Related to the respiratory epithelium and infectious diseases¹

7

OTX1

chr2

0.0005

0.0844

Associated with autism spectrum disorders [35]

8

ARMC9

chr2

0.0006

0.0873

Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway¹

9

GDNF

chr5

0.0008

0.0985

Related to the neurotrophic system¹

10

NPRL2

chr3

0.0009

0.0985

Associated with epilepsy¹

1

SNORD34

chr19

0.0002

0.0754

Predicted to act upstream of or within glucose metabolic process; insulin secretion; and reactive oxygen species metabolic process¹

2

NLRP6

chr11

0.0003

0.0754

Involved in the arginine vasopressin-mediated regulation of renal salt–water balance¹

Maintains tissue homeostasis, involved in inflammatory processes [36]

3

GALNT2

chr1

0.0003

0.0754

Encodes a member of the glycosyltransferase 2 protein family, associated in O-linked glycosylation of the immunoglobulin A1 hinge region¹

Involved in several types of metabolic diseases and cancer pathology [37]

4

SFT2D3

chr2

0.0002

0.0754

Predicted to be involved in protein transport and vesicle-mediated transport¹

5

ARFGAP1

chr20

0.0005

0.1067

Encodes a GTPase-activating protein, associated with the Golgi apparatus¹

6

FAM30A

chr14

0.0013

0.1587

Affiliated with the long noncoding lncRNA class, associated with gallbladder cancer¹

7

EFNA1

chr1

0.0024

0.1928

Comprises a subfamily of receptor protein tyrosine kinases, implicated in mediating developmental events in the nervous system and in erythropoiesis¹

8

STRADA

chr17

0.0011

0.1587

Involved in catalytic activity, mutations result in polyhydramnios, megalencephaly and symptomatic epilepsy¹

9

GMCL1

chr2

0.0012

0.1587

Encodes a nuclear envelope protein involved in spermatogenesis¹

10

PPP1R14A

chr19

0.0013

0.1587

Encodes a protein that is inhibitor of smooth muscle myosin phosphatase¹

1

KBTBD11

chr8

0.0002

0.0416

Associated with deafness¹

2

PPP1R14A

chr19

0.0002

0.0416

Encodes a protein that is inhibitor of smooth muscle myosin phosphatase¹

3

ARFGAP1

chr20

0.0003

0.0416

Encodes a GTPase-activating protein, associated with the Golgi apparatus¹

4

RIPOR2

chr6

0.0003

0.0416

Associated with altered methylation in trauma exposure [38] and some cancer types¹

5

FAM30A

chr14

0.0003

0.0416

Affiliated with the long noncoding lncRNA class, associated with gallbladder cancer¹

6

DLX4

chr17

0.0003

0.0416

Associated with some cancer types, neurogenesis and Alzheimer disease [39]

7

LAT

chr16

0.0003

0.0416

Related to inflammatory/immune processes¹

8

SNORD34

chr19

0.0003

0.0416

Predicted to act upstream of or within glucose metabolic process; insulin secretion; and reactive oxygen species metabolic process¹

9

POLD4

chr11

0.0003

0.0417

Associated with schizophrenia [34] and some cancer types¹

10

H19

chr11

0.0005

0.0561

Associated with cognitive impairment, Alzheimer disease [40] and some cancer types¹