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Table 3 Differentially methylated regions (DMRs) associated with maternal adverse childhood experiences (ACEs)

From: Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood

Chr

Start a

End

Width

# CpGs

Šidák p value

Mean OR

(2.5, 97.5 percentile)

Baseline maximum likelihood (95% Range) % methylated b

Maximum likelihood (95% Range) % methylation change c

Gene annotation

Feature category

Total number of ACEs

 

6

31,734,265

31,734,450

186

5

\(7.14\times {10}^{-3}\)

0.98 (0.97, 0.98)

39.42 (23.59, 51.51)

− 0.56 (− 0.72, − 0.40)

VWA7

Body

7

39,170,545

39,171,071

527

5

\(4.82\times {10}^{-8}\)

0.94 (0.93, 0.96)

84.94 (72.31, 94.29)

− 0.81 (− 1.53, − 0.22)

POU6F2

Body

11

316,088

316,505

418

4

\(5.72\times {10}^{-10}\)

0.95 (0.93, 0.97)

39.69 (17.51, 61.91)

− 1.05 (− 1.41, − 0.66)

–

–

16

84,346,770

84,346,979

210

4

\(3.98\times {10}^{-6}\)

1.02 (1.02, 1.03)

63.93 (61.88, 67.33)

0.50 (0.44, 0.54)

WFDC1

Body

Total number of ACEs categorized

 

4–10 versus 0 total ACEs

 

7

73,894,932

73,895,279

348

5

\(6.85\times {10}^{-13}\)

1.20 (1.11, 1.29)

33.81 (25.07, 42.00)

4.12 (2.02, 6.36)

GTF2IRD1

5’UTR

Mutually adjusted ACEs

 

Emotional abuse

 

3

126,007,325

126,007,564

240

4

\(3.26\times {10}^{-7}\)

0.69 (0.61, 0.83)

28.89 (22.20, 37.96)

− 7.04 (− 8.49, − 4.36)

–

 

8

95,962,132

95,962,512

381

6

\(1.36\times {10}^{-6}\)

1.41 (1.33, 1.50)

44.33 (31.06, 59.17)

9.48 (7.36, 11.45)

TP53INP1

TSS1500

15

74,218,577

74,218,970

394

9

\(6.76\times {10}^{-10}\)

1.23 (1.16, 1.36)

46.63 (34.23, 61.96)

5.12 (3.75, 6.87)

LOXL1,

LOXL1-AS1

TSS200, 5'UTR, 1st Exon

Sexual abuse

 

2

128,453,260

128,453,533

274

4

\(1.17\times {10}^{-5}\)

0.44 (0.30, 0.54)

26.07 (14.01, 31.99)

− 12.02 (− 14.43, − 9.04)

–

–

4

4,543,812

4,544,026

215

8

\(6.96\times {10}^{-4}\)

1.17 (1.10, 1.25)

2.45 (1.18, 5.48)

0.38 (0.25, 0.61)

STX18-AS1

TSS200, TSS1500

7

27,155,036

27,155,283

248

5

\(3.01\times {10}^{-4}\)

0.86 (0.83, 0.90)

95.28 (92.40, 98.32)

− 0.65 (− 1.04, − 0.35)

HOXA3

5’UTR, TSS1500

7

38,350,921

38,351,155

235

4

\(1.17\times {10}^{-4}\)

0.61 (0.58, 0.65)

13.52 (9.83, 17.25)

− 4.83 (− 5.94, − 3.69)

–

–

12

2,339,439

2,339,663

225

3

\(2.17\times {10}^{-4}\)

0.83 (0.77, 0.87)

44.98 (40.00, 51.01)

− 4.70 (− 6.19, − 3.43)

CACNA1C

Body

20

36,148,505

36,149,456

952

34

\(<1.0\times {10}^{-13}\)

0.87 (0.79, 0.94)

58.73 (41.48, 75.15)

− 3.41 (− 5.80, − 1.48)

BLCAP

5’UTR, TSS1500, TSS200

Emotional neglect

 

6

31,733,847

31,734,148

302

8

\(4.07\times {10}^{-5}\)

0.82 (0.77, 0.85)

80.46 (56.65, 92.09)

− 2.95 (− 4.92, − 1.53)

VWA7

Body

17

40,274,703

40,274,741

39

5

\(7.38\times {10}^{-4}\)

0.86 (0.81, 0.92)

95.38 (93.90, 96.93)

− 0.86 (− 1.33, − 0.39)

HSPB9, KAT2A

TSS200, TSS1500

Physical neglect

 

1

234,367,322

234,367,587

266

4

\(4.84\times {10}^{-5}\)

1.56 (1.50, 1.64)

70.24 (59.59, 80.26)

8.22 (6.97, 9.59)

SLC35F3

Body

6

28,829,230

28,829,689

460

19

\(6.06\times {10}^{-5}\)

1.27 (0.98, 1.58)

83.40 (31.61, 96.99)

1.19 (− 0.45, 2.58)

LINC01623

Body

6

32,063,487

32,064,307

821

26

\(<1.0\times {10}^{-13}\)

1.51 (1.17, 1.99)

43.51 (12.35, 78.93)

8.48 (3.03, 16.83)

TNXB

Body

11

6,291,625

6,292,512

888

7

\(8.09\times {10}^{-10}\)

1.67 (1.42, 2.06)

82.46 (72.74, 86.98)

6.27 (4.12, 10.16)

CCKBR

Body

11

67,383,425

67,383,863

439

7

\(2.06\times {10}^{-5}\)

1.43 (1.34, 1.60)

42.56 (29.66, 63.22)

7.94 (6.31, 10.23)

–

 

11

68,782,024

68,782,260

237

5

\(5.73\times {10}^{-6}\)

1.72 (1.37, 2.39)

55.43 (39.63, 75.69)

11.27 (5.05, 20.37)

MRGPRF

Body

13

20,751,257

20,751,994

738

5

\(5.23\times {10}^{-12}\)

1.46 (1.40, 1.62)

55.70 (36.31, 88.56)

8.56 (3.16, 13.07)

–

 

15

42,371,635

42,371,935

301

5

\(1.44\times {10}^{-3}\)

1.35 (1.24, 1.47)

84.80 (72.88, 92.42)

3.24 (1.97, 5.06)

PLA2G4D

Body

18

44,562,067

44,562,137

71

6

\(4.78\times {10}^{-4}\)

1.48 (1.32, 1.63)

97.69 (97.08, 98.31)

0.68 (0.65, 0.71)

KATNAL2, TCEB3B

5’UTR, TSS200

Domestic violence in household

 

4

4,543,474

4,544,026

553

11

\(2.81\times {10}^{-7}\)

0.86 (0.83, 0.91)

2.44 (1.19, 5.20)

− 0.33 (− 0.49, − 0.17)

STX18, STX18-AS1

TSS200, TSS1500, Body, 1st Exon, 5'UTR,

6

31,803,880

31,804,462

583

7

\(4.15\times {10}^{-6}\)

1.40 (1.30, 1.57)

26.18 (2.22, 63.76)

3.79 (1.11, 6.02)

SNHG32, SNORD52

5’UTR, TSS1500

11

368,351

368,761

411

12

\(1.42\times {10}^{-6}\)

1.24 (1.15, 1.34)

31.02 (10.81, 71.04)

3.71 (1.67, 6.52)

B4GALNT4

TSS1500

12

4,918,848

4,919,139

292

4

\(5.34\times {10}^{-5}\)

0.63 (0.54, 0.71)

3.83 (2.60, 6.63)

− 1.32 (− 2.09, − 0.74)

KCNA6

5’UTR, 1st Exon

Substance abuse in household

 

6

33,245,619

33,245,780

162

10

\(4.30\times {10}^{-3}\)

1.10 (1.04, 1.15)

54.43 (26.50, 76.76)

2.31 (1.02, 3.66)

B3GALT4

1st Exon

17

46,018,923

46,019,185

263

6

\(4.36\times {10}^{-8}\)

1.32 (1.24, 1.42)

2.14 (1.55, 3.21)

0.67 (0.46, 0.83)

PNPO

1st Exon, Body, 5’UTR

19

35,615,444

35,615,639

196

3

\(4.10\times {10}^{-5}\)

1.41 (1.31, 1.49)

5.59 (2.33, 10.33)

1.92 (1.04, 2.86)

LGI4

3’UTR

Mental illness in household

 

11

67,383,425

67,383,863

439

7

\(1.90\times {10}^{-9}\)

0.65 (0.55, 0.73)

42.56 (29.66, 63.22)

− 9.21 (− 11.04, − 6.06)

–

 

15

81,426,525

81,426,670

146

6

\(8.92\times {10}^{-3}\)

1.75 (1.65, 1.86)

36.18 (27.69, 43.25)

13.57 (11.17, 14.83)

CFAP161

TSS200, 1st Exon, 5’UTR

18

77,905,391

77,905,800

410

8

\(9.10\times {10}^{-11}\)

0.67 (0.59, 0.78)

33.49 (22.27, 46.26)

− 7.87 (− 9.87, − 5.23)

LOC100130522

TSS1500, TSS200

19

38,794,635

38,794,894

260

5

\(7.41\times {10}^{-5}\)

0.74 (0.63, 0.80)

26.57 (11.62, 54.30)

− 4.79 (− 6.47, − 2.87)

C19orf33, YIF1B

1st Exon, 3’UTR, 5’UTR, TSS200

19

50,191,390

50,191,732

343

5

\(3.80\times {10}^{-5}\)

1.24 (1.15, 1.35)

68.29 (50.47, 93.68)

4.39 (0.90, 6.33)

C19orf76, PRMT1

TSS1500, Body, 3’UTR

Household member incarcerated

 

6

33,048,086

33,048,968

883

23

\(3.77\times {10}^{-13}\)

1.56 (1.18, 2.11)

86.34 (68.71, 97.78)

3.85 (0.62, 7.80)

HLA-DPB1

Body

7

27,170,600

27,171,155

556

12

\(2.98\times {10}^{-6}\)

0.74 (0.67, 0.82)

29.67 (15.09, 60.04)

− 5.78 (− 7.90, − 4.79)

HOXA4

TSS1500

17

47,092,026

47,092,273

248

5

\(2.79\times {10}^{-6}\)

1.42 (1.26, 1.59)

67.00 (59.08, 75.38)

8.25 (4.82, 10.90)

IGF2BP1

Body

Parents divorced

  

5

158,531,180

158,531,512

333

4

\(3.63\times {10}^{-6}\)

0.83 (0.82, 0.84)

40.29 (14.60, 73.47)

− 3.19 (− 3.68, − 2.37)

–

–

15

101,093,778

101,093,901

124

3

\(9.18\times {10}^{-6}\)

0.47 (0.44, 0.53)

72.80 (63.78, 84.96)

− 19.57 (− 23.68, − 12.14)

–

–

20

61,590,799

61,591,067

269

3

\(9.70\times {10}^{-6}\)

2.90 (2.77, 3.02)

44.52 (41.39, 47.66)

26.98 (26.05, 27.91)

SLC17A9

Body

  1. Effects of maternal ACEs were modeled linearly or categorically as 0, 1–3, or 4–10 ACEs; effects of individual ACEs were estimated in a mutually adjusted model
  2. ahg19 assembly
  3. bBaseline measures were obtained from fitted models by plugging in mean values for continuous variables or most-frequently observed values for categorical variables. Thus the baseline prediction is for a female child with gestational age of 273.36 days, whose mother had 1.19 previous births with gestational age \(\ge\) 24 weeks, did not smoke during pregnancy, was married at time of birth, had educational attainment at or below 6th grade, was 25.73 years old at time of birth, and whose cord blood cell type composition was 18.94% CD4 + T cells, 9.12% CD8 + T cells, 0.73% natural killer cells, 18.33% B Cells, 10.92% monocytes, 40.63% granulocytes, 1.33% nucleated red blood cells
  4. cExposed measures were obtained by plugging in the same values used to represent the mean/most frequently observed individual for baseline and setting exposure variables to 1. The Differences between exposed and baseline methylation were Monte Carlo simulated using 3000 draws from a multivariate normal distribution, followed by inverse logit transformation and subtraction