Table 2 Studies description table.

From: Exploring the association between serotonin transporter promoter region methylation levels and depressive symptoms: a systematic review and multi-level meta-analysis

First author, year

N tot

(ne, nc)

Age

Sex

(female %)

Ethnicity

(as reported in papers)

Type of depression

Severity of depression

Primary disorder

Depression scale used

Comorbidity

Controls Used

Sample

Methylation technique

Single-CpG resolution option?

CpG Data Type Used for Effect Computation

Number of CpGs

(/74 CpG in the CpG island)

Genomic location

GRCh38/hg38 conversion

UCSC Liftover - 30 23_ _ _ _

(for ref. 799 bp CpG island: 5 370 – 6 168)

Study Effect Sizes

Expression tested?

Meta-analysis 1 – Depression occurrenceGroup comparisons (12 studies, 127 effects, 2028 participants)

Bruzzone,

2024

387

(90, 297)

29.6

63.9

EUR

MDD

Moderate

all

MDD

BDI

HAM-D17

Anx., chilhood trauma

Healthy

Blood peri or WBC

Pyroseq.

PyroMark Q96

Y

Single

4

GRCh38/hg38

30,236,071;

30,236,083;

30,236,088;

30,236,090

6090; 6088;

6083; 6071

4

N

Bakusic,

2020

138

(80, 58)

45.4

56.5

n/a

MDD

Moderate

average

MDD

SCID

n/a

Healthy

Blood peri

Pyroseq.

PyroMark Q24

Y

Single

23 CpG

GRCh38/hg38

GenBank NG_011747

6101; 6090;

6088; 6083;

6071; 6036;

6002; 5998;

5984; 5975;

5973; 5968;

5956; 5952;

5939; 5910;

5906; 5904;

5897; 5892;

5888; 5886;

5871; 5867;

5852

23

N

Schiele,

2019

60

(32, 28)

34.3

78.3

CA

Comord. MDD

n/a

PD

SCID

Ago., MDD, social Anx., phobias

PD without MDD

Blood peri

Pyroseq.

Y

Single

9

GRCh38/hg38

30,236,071;

30,236,083;

30,236,088;

30,236,090;

30,236,101;

30,236,120;

30,236,125;

30,236,141;

30,236,156

6156; 6141;

6125; 6120;

6101; 6090;

6088; 6083;

6071

9

N

Lam,

2018

\(302_{{(95,\, {207})}^{\rm{b}}}\)

73.2

62.5

CA

MDD

> Mild all

+

Moderate

average

MDD

MINI

CES-D

Dementia, Anx., ischemic diseases, cancer, thyroid disease, diabetes, asthma

Healthy elders

WBC

MALDI-based

Agena

N

Averaged per unit

10 units/20 CpG

GRCh38/hg38

Reg.:

30,235,734–

30,236,068

6036; 5984;

5975/73;

5956/52;

5939;

5909/891;

5886/84;

5870/60;

5795;

5768/65

10

N

Schneider,

2018

298

(122, 176)

36.3

53

EUR

MDD

Moderate

average

MDD

SCID

n/a

Healthy

Blood peri

BS - PCR

EZ-DNA methylation kit -ESME software

Y

Single

8d

GRCh38/hg38

-

AluJb

6593; 6587;

6571; 6511;

6509; 6500;

6496;

7

N

Shi,

2017

151

(96, 55)

31 med.

(21-47)

60.3

CHA

MDD

Severe

all

MDD

SCID

HAM-D24

n/a

Healthy

Blood peri

Pyroseq.

Pyro Q-CpG

Y

Single

6

GRCh37/hg19

28,562,957;

28,562,970;

28,562,974;

28,562,986;

28,562,991;

28,562,993

5975; 5973;

5968; 5956;

5952; 5939

6

N

Iga,

2016

57

(28, 29)

43.6

71.9

JA

MDD

Moderate

average

MDD

SCID

Diabetes,

hypertension,

gastritis

Healthy

WBC

Pyroseq.

PyroMark Q24

Y

Single

9

GRCh37/ hg19

GenBank NC_000017.10

6156; 6141;

6125; 6120;

6101; 6090;

6088; 6083;

6071

9

Y

Won,

2016

84

(35, 49)

40.8

70.2

KA

MDD

Moderate

average

MDD

SCID

Suicide, drug abuse

Healthy

Blood peri

Pyroseq.

Pyrosequencing Assay Design Software

Y

Single

5

n/a

−34 to −5 bp relative to the TSS

5732; 5728;

5714; 5705;

5703

5

N

Booij,

2015

69

(33, 36)

37.7

63.8

n/a

MDD

Severe

all

MDD

SCID

n/a

NO psychiatric comorb.

Healthy

Blood peri

Pyroseq.

PyroMark Q24

Y

Average

all + specific sites

11d

n/a

214 to 625 bp region upstream of TSS

6167–6036;

6167/56;

6090/88;

3

Y

Okada,

2014

100

(50, 50)

40.3

46

JA

MDD

Moderate

all

MDD

MINI

n/a

Healthy

Blood peri

MALDI-based

Agena

N

Single

29 units / 47 CpG

GRCh37/hg19

Reg.:

28,562,388–

28,563,186

spe. CpG sites: n/a

Reg:

5 370 - 6 168

29

N

Kim,

2013

286

(80, 206)

64.5

40.9

n/a

PSD

Moderate

average

PSD

MINI

n/a

NO dementia, Parkinson, brain tumor, epilepsy, psychosis, substance dependence; severe physical illnesses limiting movement prior PSD

Healthy

Blood peri

Pyroseq.

Pyro Q-CpG

Y

Single

7

n/a

−479 to −350 bp relative to the TSS

6141; 6125;

6101; 6090;

6088; 6083;

6071

7

N

Xu,

2013

96

(36, 60)

28.2

80.2

CHA

Comorb. depr.

Moderate

average

SLE

SCID

Depr.

SLE without depr.

WBC

BS - PCR

Shanghai Sangon Biological Engineering Technology & Services Co. Ltd.

Y

Single

15

d

n/a

GenBank: EF179203.1

7150; 7146;

7133; 7105;

7097; 7080;

7070; 7068;

7066; 7044;

7036; 7029;

7018; 7002;

6995

15

N

Systematic review only - Depression occurrence Group comparisons (2 studies, 413 participants)

Moon,

2022

221

64.0

78.2

KA

MDD

Moderate

all

MDD

HAM-D17

n/a

NO cancer, unstable psychiatric features, history of substance abuse, neurologic illnesses, SCZ, BD, primary diagnoses of adjustment disorder, PTSD, psychotic sympt., pregnancy

Only MDD

Blood peri

Pyroseq.

PyroMark

Y

Single

9

GRCh37/ hg19

28,563,090;

28,563,102;

28 563,107;

28,563,109;

28,563,120;

28,563,139;

28,563,144;

28,563,160;

28,563,175

6156; 6141;

6125; 6120;

6101; 6090;

6088; 6083;

6071

-

Y

Philibert,

2008

192

(25, 167)

40.6

50

AFA, HA, others

MDD

n/a

MDD

SCID

Alcohol dependence

Healthy

lymphoblast cell lines

BS - PCR

MassARRAY

N

-

53 units/ 71 CpG

NCBI36/hg18

Reg.:

25,586,414 –

25,587,412

Reg.:

5270–6268

-

Y

Meta-analysis 2 – Depression severity Correlations/Regressions (14 studies, 116 effects, 2296 participants)

Rivera,

2024

91

24.0

50.5

RWD

Depr. Sympt. + MDD

Mild

average

No diagnosis or MDD

PROMIS-29

Childhood adversity

MDD + Healthy

capillary Blood peri

Microarray

Illumina Infinium MethylationEPIC microarray

N

not in this case

Average

n/a

n/a

n/a

1

N

Comtois-Cabana,

2023

156

24.1

0

n/a

Depr. Sympt. + MDD

Mild

average

No diagnosis or MDD

BDI-II

Drug use

MDD + Healthy

Saliva

BS – PCR

EZ-DNA methylation Gold Kit - EpiTYPER MassARRAY

Y

Average

per unit

31 units/87 CpG

GRCH37/hg19

Reg. 1:

28,563,054–

28,563,424;

Reg. 2:

28,562,783–

28,563,020;

Reg. 3:

28,562,388–

28,562,751

6406; 6235;

6167; 6141;

6036; 5896/91;

5886/84/70;

5866; 5851;

5845/43;

5837–5829;

5808, 5768/65;

5733/31;

5719–5699;

5688–5673;

5667/65; 5654;

5641; 5 578;

5554/49;

5518/11;

5503; 5489;

5481/74/71;

5456; 5447;

5417; 5394;

5383; 5374/70

31

N

Vidovic,

2023

25

52.1

64.0

CA

MDD

Moderate to Severe

average

MDD

BDI-II

IDS-C

Anx.

Only MDD

Blood peri

BS – PCR

EpiTect Fast Bisulfite - MiniSeq Mid Output Kit

N

Average

2

GRCH37/hg19

Reg. 1:

28,562,753–

28,563,050

Reg. 2:

28,563,277–

28,563,552

Reg. 1:

5735–6032

Reg. 2:

6259 –

6534

2c

N

Timmers,

2022

117

46.6

65.8

n/a

Depr. Sympt. + MDD

Mild

average

Dystonia

BDI

Depr.

Dystonia with/without Depr. Sympt.

Blood peri

Pyroseq.

PyroMark Q24

Y

Single

20

n/a

−213 to −69 bp relative to the transcriptional start

5910; 5906;

5904; 5896;

5891; 5886;

5884; 5870;

5865; 5850;

5845; 5843;

5837; 5835;

5832; 5830;

5808; 5796;

5779; 5776

20

N

Sanwald,

2021

146

38.7

65.1

n/a

MDD

Moderate to Severe

average

MDD

BDI-II

MADRS

Alcohol abuse (n=2), sexual dysfunction (n=1)

Only MDD

Blood peri

MALDI-based

Agena

N

Average2 factors

29 units / 71 CpG

GRCh38/hg38

Reg. 1 :

30,235,345–

30,235,765

Reg. 2:

30,235,734–

30,236,068

Reg. 1 :

5345–5765

Reg. 2:

5734–6068

2c

N

Schiele,

2021

236

34.3

78.3

CA

MDD treated since min.6w

Severe

average

MDD

BDI

HAM-D21

PD and/or ago. (n=11), social phobia (n=7), stress-related disorder (n=5), somatoform (n=7), OCD (n=2)

Only MDD

Blood peri

BS – PCR

Epigenetic Sequencing Methylation analysis software

Y

Average

9

GRCh38/hg38

30,236,071;

30,236,083;

30,236,088;

30,236,090;

30,236,101;

30,236,120;

30,236,125;

30,236,141;

30,236,156

Reg.:

6071–6156

1c

N

Bakusic,

2020

138

45.4

56.5

n/a

MDD

Moderate

average

MDD

HAM-D17

n/a

MDD + Healthy

Blood peri

Pyroseq.

PyroMark Q24

Y

Average

all + specific sites

5 units / 23 CpG

GRCh38/hg38

GenBank NG_011747

6101;

6088;

6101/071

3

N

Shi,

2017

96

31 med.

(21–47)

60.3

CHA

MDD

Severe

all

MDD

HAM-D24

n/a

Only MDD

Blood peri

Pyroseq.

Pyro Q-CpG

Y

Single

6

GRCh37/hg19

28,562,957;

28,562,970;

28,562,974;

28,562,986;

28,562,991;

28,562,993

5975; 5973;

5968; 5956;

5952; 5939

6

N

Iga,

2016

28

45

71.4

JA

MDD

Moderate

average

MDD

HAM-D17

Diabetes, hypertension, gastritis

Only MDD

WBC

Pyroseq.

PyroMark Q24

Y

Single

9

GRCh37/hg19

GenBank NC_000017.10

6156; 6141;

6125; 6120;

6101; 6090;

6088; 6083;

6071

9

Y

Duman,

2015

67

28.5a

0

CA

Depr. Sympt.

Mild

average

-

BDI-II

-

Only MDD

WBC

MALDI-based

Sequenom Epityper

N

Average

all + per factor

3 units / 26 CpG

n/a

Reg.:

5270–

6268

3 factors

3

Y

Lei,

2015

99

48.3

100

AFA

Depr. Sympt.

Mild

average

-

CES-D

n/a

Healthy

Blood peri

Microarray

Illumina 450K Human Methylation Beadchip

N

not in this case

Average

7 units

n/a

Cg27569822,

Cg10901968,

Cg26741280,

Cg25725890,

Cg05016953,

Cg14692377,

Cg03363743

6139/090 +

6120/071 +

6101/50 +

6037/5 988 +

5796/47 +

5668/19 +

5457/08

1

N

van der Knaap,

2015

939

16.2

51.7

Dutch

Depr. Sympt..

n/a

-

YSR

Internalizing, Anx., Depr.

Healthy

Blood peri

MALDI-based

Agena

N

Average

11 units

GRCh37/hg19

Reg.:

28,562,388–

28,563,186

Reg:

5370–

6168

1

N

Okada,

2014

50

40.3

46

JA

MDD

Moderate

all

MDD

HAM-D17

n/a

Only MDD

Blood peri

MALDI-based

Agena

N

Average

per unit

29 units/47 CpG

GRCh37/hg19

Reg.:

28,562,388–

28,563,186

spe. CpG sites: n/aReg:

5370–

6168

29

N

Kang,

2013

108

54.9

76.4

n/a

MDD

Moderate

average

MDD

HAM-D17

n/a

Only MDD

Blood peri

Pyroseq.

Pyro Q-CpG

Y

Single

7 CpG

n/a

−479 to −350 bp relative to the TSS;

6141; 6125;

6101; 6090;

6088; 6083;

6071

7

N

  1. Ago. Agoraphobia, AFA African-American, Anx. Anxiety, BD Bipolar Disorder, BDI Beck Depression Inventory, Bloodperi peripheral Blood, BS-PCR Bisulphite polymerase chain reaction, CA Caucasian, CES-D Centre for Epidemiological Studies-Depression scale (CES-D), CHA Chinese Han, CIDI Composite International Diagnostic Interview, CpG Cytosine phosphate guanine, Depr. Depression, EUR European ancestry, HA Hispanic, HAM-D Hamilton Depression Rating Scale, JA Japanese, KA Korean, MADRS Montgomery-Åsberg Depression Rating Scale, MALDI-based Matrix-Assisted Laser Desorption/Ionisation-based, MDD Major Depressive Disorder, MINI: Mini International Neuropsychiatric Interview, N:No, n/a: Not available, OCD: Obsessive-Compulsive Disorder, PD: Panic Disorder, PSD: Post Stroke Depression, PTSD: Post-Traumatic Stress Disorder, RWD Rwandan, SCID-I Structured Clinical Interview for DSM-5, SCZ Schizophrenia, Sympt. Symptoms, SLE Systemic lupus erythematosus, TSS Transcription Start Site, WBC White Blood Cell, Y Yes, YSR Youth Self-Report.
  2. aAge of the full sample reported in the study.
  3. bNot the same sample size for all computed effect sizes.
  4. cMultiple questionnaires were used to evaluated depression severity thus effects were first pooled per CpG site/unit – only average effects are reported.
  5. dRegion analysed in the promoter but not in the 799bp CpG island.