5' 3'

Online Supplementary Data

Assayed CpG sites in the five stress-related genes

BDNF gene

Supplementary Figure S1. A schematic illustration of the assayed CpG sites in the BDNF gene in two twin studies. A total of 78 CpG sites were

assayed in the BDNF gene. Red represents the CpG sites assayed in the THS only (7 sites), blue represents the CpG sites assayed in the MMS only (68 sites), and green represents CpG sites assayed in both studies (3 sites). TSS: transcription start site.

TSS

5’ 3’

+2000 -1000

-2000 +1000

-2433 +1

Genomic position (bp)

+10000 +20000 +23348 +40000 +62857

NR3C1 gene

Supplementary Figure S2. A schematic illustration of the assayed CpG sites in the NR3C1 gene in two twin studies. A total of 55 CpG sites were

assayed in the NR3C1 gene. Red represents the CpG sites assayed in the THS only (23 sites), blue represents the CpG sites assayed in the MMS only (30 sites), and green represents CpG sites assayed in both studies (2 sites). TSS: transcription start site.

TSS

5’ 3’

-490 -274 +1+427 +6980

-6000 -32215

Genomic position (bp)

+25942 +124426

SLC6A4 gene

Supplementary Figure S3. A schematic illustration of the assayed CpG sites in the SLC6A4 gene in two twin studies. A total of 29 CpG sites were

assayed in the SLC6A4 gene. Red represents the CpG sites assayed in the THS only (16 sites), blue represents the CpG sites assayed in the MMS only (9 sites), and green represents CpG sites assayed in both studies (4 sites). TSS: transcription start site.

TSS

5’ 3’

-231 -3 +1 +141 +3457

-1163 -100

Genomic position (bp)

+13148 +38794 +812

MAOA gene

Supplementary Figure S4. A schematic illustration of the assayed CpG sites in the MAOA gene in two twin studies. A total of 20 CpG sites were

assayed in the MAOA gene. Red represents the CpG sites assayed in the THS only (6 sites), blue represents the CpG sites assayed in the MMS only (13 sites), and green represents CpG sites assayed in both studies (1 sites). TSS: transcription start site.

TSS

5’ 3’

-90 -10 +1 +77 +2638

-1553

Genomic position (bp)

MAOB gene

Supplementary Figure S5. A schematic illustration of the assayed CpG sites in the MAOB gene in two twin studies. A total of 15 CpG sites were

assayed in the MAOB gene. Red represents the CpG sites assayed in the THS only (7 sites), and blue represents the CpG sites assayed in the MMS only (8 sites). TSS: transcription start site.

TSS

5’ 3’

+1806 -71

-134 +1 +92 +383 +3370 +115617

Genomic position (bp)

Supplementary Table S1. Number of participants with specific type of childhood traumatic experiences in the THS and MMS

Childhood trauma THS, Male (n=168) MMS, Female (n=70)

n (%) Median (IQR) Mean ± SD n (%) Median (IQR) Mean ± SD Domains of childhood trauma

Physical abuse 58 (34.5) 2 (1 - 3) 1.9±1.2 7 (10.0) 0 (0 - 1) 0.8±1.1 Emotional abuse 38 (22.6) 1 (0 - 2) 1.6±1.4 15 (21.4) 0 (0 - 2) 1.1±1.6 Sexual abuse 20 (11.9) 0 (0 - 0) 0.2±0.8 13 (18.6) 0 (0 - 0) 0.3±1.0 General trauma 54 (32.1) 3 (1 - 4) 2.7±2.0 10 (14.3) 1 (0 - 2) 1.6±1.4 Childhood trauma

≥ 1 domain 96 (57.1) 6 (4 - 9) 6.5±3.8 30 (42.9) 2 (1 - 5) 3.8±3.7 THS: the Twin Heart Study; MMS: the Mood and Methylation Study; IQR: interquartile range.

Supplementary Table S2. Associations of specific types of childhood traumatic experiences with depressive symptoms in the THS and MMS

Childhood trauma (y/n)

THS MMS

β^* SE P^# β^* SE P^#

Domains of childhood traumatic experiences

Physical abuse 0.223 0.123 0.0698 -0.251 0.286 0.3810

Emotional abuse 0.727 0.152 <0.0001 0.902 0.241 0.0002

Sexual abuse 0.457 0.150 0.0023 0.795 0.194 <0.0001

General trauma 0.659 0.138 <0.0001 0.410 0.193 0.0339

Childhood trauma

≥ 1 domain 0.694 0.139 <0.0001 0.972 0.172 <0.0001

*Increase in BDI-II score for participants with versus without the type of childhood traumatic experiences.

#Adjusting for age, family income level, pack-year, alcohol consumption, physical activity, body mass index, and history of PTSD.

Supplementary Table S3. Association of single CpG methylation in five stress-related genes with depressive symptoms in the THS

Genomic Relative Methylation level Depressive symptoms Explained variance,

position to TSS (bp) (%, mean±SD) β SE P^* q %

BDNF (Chr11)

27743580 -1254 1.93±1.44 0.0460 0.0496 0.3531 0.4940 0.0001

27743583 -1257 4.55±1.27 -0.0274 0.0675 0.6845 0.6845 0.8150

27743619 -1293 1.95±1.00 -0.1086 0.0558 0.0514 0.1284 1.0179

27743642 -1316 2.54±1.11 0.0422 0.0552 0.4446 0.4940 0.6969

27743648 -1322 1.86±1.01 0.1227 0.0524 0.0193 0.0966 1.3736

27743651 -1325 4.78±1.20 0.2230 0.0506 0.0000 0.0001 3.5461

27743654 -1328 5.79±2.00 -0.0206 0.0247 0.4058 0.4940 0.0094

27743664 -1338 3.55±1.88 0.0379 0.0335 0.2583 0.4306 0.0057

27743673 -1347 3.99±1.96 -0.0712 0.0330 0.0311 0.1037 1.1469

27743679 -1353 4.20±1.71 0.0496 0.0373 0.1830 0.3659 0.5438

NR3C1 (Chr5)

142783528 -274 2.87±1.39 0.0665 0.0434 0.1251 0.2235 0.2614

142783531 -277 3.25±1.59 0.1199 0.0387 0.0019 0.0162 2.4006

142783537 -283 1.17±1.60 -0.0522 0.0333 0.1172 0.2235 0.6693

142783540 -286 3.11±1.84 0.0524 0.0334 0.1172 0.2235 0.6312

142783547 -293 1.62±1.55 0.0968 0.0364 0.0077 0.0387 2.5576

142783566 -312 2.72±1.44 0.0304 0.0358 0.3965 0.5135 0.4328

142783569 -315 3.23±1.48 0.1469 0.0515 0.0043 0.0270 0.0368

142783584 -330 5.90±2.33 0.0346 0.0311 0.2666 0.3920 0.0204

142783607 -353 6.39±3.27 0.0110 0.0307 0.7198 0.7616 0.0241

142783621 -367 4.32±2.66 -0.0062 0.0179 0.7312 0.7616 0.0307

142783627 -373 0.52±1.39 -0.1012 0.0420 0.0160 0.0668 2.0640

142783637 -383 0.84±1.60 0.0689 0.0301 0.0223 0.0698 0.9245

142783639 -385 1.16±1.90 -0.0344 0.0266 0.1967 0.3074 0.0773

142783655 -401 0.68±1.40 -0.0378 0.0389 0.3311 0.4599 0.1194

142783663 -409 0.68±1.52 -0.0834 0.0382 0.0290 0.0805 1.7656

142783678 -424 1.14±1.75 0.0057 0.0309 0.8530 0.8530 0.0618

142783685 -431 0.38±0.99 0.1001 0.0431 0.0203 0.0698 0.7390

142783688 -434 0.65±1.27 -0.0478 0.0368 0.1936 0.3074 0.2938

142783702 -448 1.54±2.17 0.0348 0.0196 0.0758 0.1895 0.5101

142783712 -458 1.28±1.58 -0.2199 0.0382 0.0000 0.0000 6.0677

142783716 -462 1.44±1.97 0.0097 0.0214 0.6495 0.7381 0.0688

142783730 -476 2.29±2.89 0.0778 0.0176 <0.0001 0.0001 2.6160

142783735 -481 1.49±3.30 -0.0117 0.0142 0.4108 0.5135 0.2849

142783742 -488 2.32±3.67 0.0080 0.0122 0.5106 0.6079 0.0022

142783744 -490 1.08±1.86 0.0440 0.0285 0.1230 0.2235 0.4603

SLC6A4 (Chr17)

28562957 -3 12.79±6.62 0.0150 0.0100 0.1315 0.1735 0.4035

28562970 -16 8.76±3.68 0.0263 0.0178 0.1388 0.1735 0.4594

28562974 -20 11.59±4.72 0.0214 0.0132 0.1040 0.1599 0.5911

28562986 -32 10.13±4.74 0.0249 0.0136 0.0664 0.1207 0.9274

28562991 -37 13.58±5.75 0.0166 0.0115 0.1476 0.1736 0.5910

28562993 -39 10.03±4.27 0.0183 0.0163 0.2615 0.2753 0.1851

28563002 -48 15.98±7.78 0.0166 0.0081 0.0403 0.1002 0.7740

28563016 -62 14.76±6.83 0.0190 0.0094 0.0424 0.1002 0.4702

28563020 -66 15.67±4.61 0.0290 0.0133 0.0286 0.1002 1.1166

28563054 -100 13.54±5.78 0.0216 0.0108 0.0462 0.1002 0.5101

28563089 -135 11.04±3.92 0.0227 0.0173 0.1901 0.2112 0.4180

28563101 -147 16.72±7.18 0.0204 0.0083 0.0138 0.0920 0.8248

28563106 -152 9.23±3.48 0.0470 0.0207 0.0228 0.1002 0.5941

28563108 -154 11.65±4.86 0.0581 0.0144 0.0001 0.0011 2.3053

28563119 -165 11.28±4.06 0.0309 0.0158 0.0501 0.1002 0.8322

28563138 -184 13.27±5.57 0.0338 0.0124 0.0062 0.0623 0.9192

28563143 -189 9.63±6.82 0.0077 0.0085 0.3630 0.3630 0.0177

28563159 -205 4.30±3.67 0.0335 0.0205 0.1015 0.1599 0.2044

28563174 -220 3.39±1.91 -0.0730 0.0340 0.0320 0.1002 1.4855

28563185 -231 3.02±1.75 0.0492 0.0317 0.1205 0.1721 0.9394

MAOA (ChrX)

43515402 -65 3.70±1.83 -0.0661 0.0301 0.0282 0.0494 0.1945

43515412 -55 3.73±1.61 -0.0818 0.0370 0.0272 0.0494 0.0774

43515418 -49 5.44±1.72 -0.0384 0.0324 0.2357 0.2750 0.0068

43515439 -28 4.34±1.77 -0.0342 0.0330 0.2999 0.2999 0.0117

43515444 -23 7.24±1.84 -0.0670 0.0296 0.0238 0.0494 0.3351

43515457 -10 5.61±1.80 -0.0533 0.0329 0.1051 0.1472 0.0488

43515467 1 4.67±1.93 -0.0753 0.0323 0.0197 0.0494 0.0424

MAOB (ChrX)

43741764 -71 27.93±5.49 0.0003 0.0101 0.9744 0.9744 0.1836

43741775 -82 29.86±6.66 -0.0095 0.0087 0.2778 0.9722 0.0678

43741781 -88 54.38±6.68 -0.0006 0.0092 0.9480 0.9744 0.0004

43741785 -92 47.64±7.65 0.0040 0.0078 0.6098 0.9744 0.0834

43741806 -113 46.52±9.19 -0.0030 0.0058 0.6076 0.9744 0.0133

43741815 -122 46.08±8.87 0.0132 0.0055 0.0162 0.1131 1.2798

43741827 -134 38.32±6.74 -0.0004 0.0085 0.9623 0.9744 0.5611

*Adjusted for twin age, family income level, pack-year, alcohol consumption, physical activity, body mass index, and history of PTSD. TSS: transcription start site.

Supplementary Table S4. Association of single CpG site methylation in five stress-related genes with depressive symptoms in the MMS

Genomic Relative Methylation level Depressive symptoms Explained

variance, %

position to TSS (bp) (%, mean±SD) β SE P^* q

BDNF (Chr11)

27679469 62857 92.65±0.83 -0.1033 0.0907 0.2550 0.4415 1.2919

27679632 62694 94.26±0.59 -0.1632 0.1522 0.2836 0.4795 0.0841

27679729 62597 90.16±1.15 0.1536 0.0688 0.0255 0.0948 5.8200

27680480 61846 89.18±1.03 0.0366 0.0707 0.6043 0.7548 0.3484

27681475 60851 90.50±0.81 0.6100 0.1328 <0.0001 0.0003 5.8037

27683959 58367 86.62±1.11 0.0431 0.0830 0.6038 0.7548 0.0115

27695210 47116 91.10±0.80 0.1177 0.0911 0.1963 0.3872 1.3316

27696004 46322 90.64±0.91 -0.0354 0.0872 0.6847 0.7717 1.4975

27701991 40335 90.42±0.89 -0.2370 0.0880 0.0071 0.0502 3.5635

27718978 23348 40.56±6.54 -0.0598 0.0212 0.0048 0.0413 0.5307

27720709 21617 2.39±0.37 -0.1332 0.1348 0.3232 0.5215 0.0374

27721088 21238 6.29±0.92 0.1211 0.0718 0.0919 0.2250 2.5023

27721222 21104 8.12±0.84 0.0474 0.0981 0.6292 0.7548 0.2092

27721270 21056 2.94±0.31 -0.6717 0.2346 0.0042 0.0413 1.7000

27721277 21049 2.04±0.22 -0.6346 0.3123 0.0421 0.1108 0.7050

27721280 21046 5.42±0.97 -0.2257 0.0750 0.0026 0.0413 2.7458

27721350 20976 6.49±0.69 0.0400 0.0873 0.6465 0.7548 0.0005

27721668 20658 4.19±0.62 0.0423 0.1234 0.7316 0.7979 0.7138

27722037 20289 2.52±0.42 -0.2653 0.2091 0.2046 0.3917 0.1908

27722060 20266 4.62±0.65 -0.0818 0.1034 0.4287 0.6131 0.5372

27722063 20263 3.95±0.52 0.0656 0.1438 0.6485 0.7548 0.1816

27722066 20260 2.12±0.24 -0.8416 0.3959 0.0335 0.0991 5.2834

27722523 19803 3.31±0.22 -0.3827 0.2800 0.1717 0.3585 1.3610

27722549 19777 1.67±0.12 -1.4392 0.5946 0.0155 0.0791 3.7080

27722617 19709 6.53±0.66 0.1137 0.1208 0.3469 0.5354 0.4906

27722620 19706 4.62±0.69 0.1266 0.1009 0.2097 0.3917 2.0977

27722636 19690 3.55±0.46 -0.1882 0.1811 0.2987 0.4932 0.8303

27722638 19688 3.61±0.53 -0.0979 0.1588 0.5376 0.7127 0.1518

27722722 19604 7.06±0.89 -0.0998 0.0832 0.2304 0.4194 0.2746

27722774 19552 2.94±0.42 0.4595 0.1928 0.0172 0.0814 2.5400

27722889 19437 5.39±0.68 -0.1482 0.1007 0.1412 0.3132 0.1416

27722971 19355 4.23±0.48 -0.2085 0.1302 0.1094 0.2575 1.7319

27723075 19251 2.40±0.32 -0.4876 0.2152 0.0235 0.0948 0.5165

27723128 19198 2.63±0.21 -0.7945 0.3076 0.0098 0.0633 1.2754

27723190 19136 2.16±0.19 -1.3518 0.4274 0.0016 0.0413 3.6813

27723214 19112 4.64±0.52 -0.0296 0.1352 0.8268 0.8618 0.3049

27723218 19108 6.04±0.86 -0.2087 0.0947 0.0275 0.0948 1.2989

27723237 19089 2.03±0.27 -0.7264 0.3105 0.0193 0.0857 1.3127

27723245 19081 3.96±0.39 0.1019 0.1671 0.5420 0.7127 0.6078

27723290 19036 6.14±1.24 -0.0755 0.0640 0.2376 0.4218 0.0008

27723385 18941 5.03±0.84 -0.1362 0.1018 0.1808 0.3668 0.0044

27723409 18917 4.02±0.42 0.4050 0.1873 0.0306 0.0959 1.2211

27732958 9368 88.27±1.28 0.1294 0.0731 0.0766 0.1942 8.7329

27739827 2499 9.24±1.70 -0.129 0.0587 0.0281 0.0948 0.9168

27740078 2248 6.99±0.87 0.0200 0.0800 0.8023 0.8502 0.1566

27740161 2165 2.92±0.34 -0.0302 0.2343 0.8975 0.9104 0.0293

27740495 1831 4.64±0.52 -0.3571 0.1697 0.0354 0.1005 1.1882

27740813 1513 2.71±0.48 0.6501 0.2329 0.0052 0.0413 1.7975

27740876 1450 2.13±0.44 0.2217 0.2332 0.3419 0.5354 0.8961

27741077 1249 3.99±0.54 0.1274 0.1617 0.4307 0.6131 0.7636

27741916 410 4.97±0.71 0.2919 0.1207 0.0156 0.0791 1.5931

27742060 266 15.25±2.27 -0.0260 0.0331 0.4318 0.6131 0.0378

27742138 188 5.56±0.60 -0.1254 0.1360 0.3567 0.5389 0.0722

27742219 107 5.19±1.06 0.1453 0.0915 0.1124 0.2575 0.3305

27742355 -29 5.43±0.86 -0.0330 0.0920 0.7200 0.7979 0.6874

27742365 -39 4.00±0.64 -0.0483 0.1466 0.7417 0.7979 3.3950

27742369 -43 8.38±2.51 0.0912 0.0423 0.0311 0.0959 4.3549

27742435 -109 46.14±5.12 0.0122 0.0161 0.4501 0.6266 0.9891

27742454 -128 31.38±5.02 0.0088 0.0176 0.6177 0.7548 0.0447

27742832 -506 22.86±6.56 -0.0198 0.0144 0.1696 0.3585 1.2963

27743258 -932 2.88±0.40 0.0919 0.1817 0.6130 0.7548 0.0061

27743348 -1022 3.59±0.50 -0.1177 0.1628 0.4696 0.6412 0.9947

27743580 -1254 15.7±2.91 0.0590 0.0267 0.0270 0.0948 0.2539

27743619 -1293 5.12±0.91 -0.3055 0.1034 0.0031 0.0413 3.8489

27743664 -1338 3.58±0.40 -0.0238 0.2334 0.9187 0.9187 2.2310

27744049 -1723 14.25±1.67 -0.1818 0.0637 0.0043 0.0413 1.1745

27744363 -2037 6.49±0.95 -0.1533 0.0753 0.0417 0.1108 1.6130

27744490 -2164 2.22±0.18 -1.1285 0.3960 0.0044 0.0413 4.8135

27744557 -2231 4.12±0.86 0.0228 0.1110 0.8375 0.8618 0.0381

27744675 -2349 8.31±1.92 -0.1186 0.0487 0.0148 0.0791 2.5294

27744759 -2433 13.11±1.43 0.0245 0.0572 0.6685 0.7656 0.0035

NR3C1 (Chr5)

142658828 124426 94.29±0.49 0.0908 0.1784 0.611 0.8067 5.3067

142692961 90293 91.03±0.94 0.0010 0.0782 0.9899 0.9899 0.7555

142729913 53341 63.38±2.40 0.2278 0.0434 <0.0001 <0.0001 4.5566

142740314 42940 90.33±0.80 -0.4190 0.1045 0.0001 0.0005 2.1821

142757011 26243 92.80±0.69 -0.1647 0.0883 0.0621 0.1419 0.8415

142757312 25942 90.99±0.75 -0.0556 0.1154 0.6302 0.8067 0.0201

142776274 6980 87.50±3.39 -0.0805 0.0310 0.0095 0.0303 2.6800

142780254 3000 94.48±0.50 0.1247 0.1454 0.3909 0.5957 0.2265

142780693 2561 92.49±0.99 -0.1102 0.0811 0.1742 0.3279 0.0040

142781498 1756 34.48±4.59 0.0032 0.0208 0.8768 0.9353 0.1855

142781723 1531 8.77±1.29 0.1471 0.0534 0.0059 0.0243 3.2686

142781736 1518 9.50±1.48 0.1072 0.0450 0.0171 0.0498 0.7537

142782072 1182 2.61±0.35 -0.6340 0.1794 0.0004 0.0026 3.5305

142782791 463 5.75±0.54 0.2432 0.1467 0.0973 0.1946 0.9205

142782827 427 3.91±0.50 -0.4228 0.1616 0.0089 0.0303 1.0082

142783621 -367 4.27±0.57 -0.0931 0.1270 0.4636 0.6600 0.0295

142783639 -385 1.63±0.19 -1.2059 0.4394 0.0061 0.0243 4.0806

142783843 -589 1.69±0.13 -3.3267 0.6465 <0.0001 <0.0001 3.4131

142784222 -968 3.06±0.37 0.0071 0.2281 0.9753 0.9899 0.3453

142784323 -1069 5.40±0.50 0.0363 0.1518 0.8109 0.9267 0.0022

142784382 -1128 5.26±0.54 -0.0387 0.1224 0.7518 0.891 0.2579

142784462 -1208 1.63±0.14 -2.9798 0.5587 <0.0001 0.0001 5.7343

142784522 -1268 3.45±0.41 -0.2135 0.2141 0.3187 0.5556 0.6262

142784721 -1467 7.24±0.80 -0.3554 0.1161 0.0022 0.0117 1.5986

142784982 -1728 2.27±0.20 -0.5717 0.3290 0.0823 0.1756 0.0620

142785172 -1918 2.30±0.19 0.0692 0.4229 0.8699 0.9353 0.0846

142785258 -2004 6.89±0.89 0.0666 0.0759 0.3804 0.5957 0.1338

142786405 -3151 92.43±0.63 0.0438 0.1298 0.7355 0.8910 2.6336

142788776 -5522 93.66±0.46 -0.3594 0.1815 0.0477 0.1173 0.5742

142814827 -31573 3.90±0.42 0.3794 0.1673 0.0234 0.0623 1.8538

142815463 -32209 91.72±0.68 -0.1055 0.1083 0.3299 0.5556 0.5133

142815469 -32215 89.73±1.24 0.0470 0.0657 0.4743 0.6600 1.8086

SLC6A4 (Chr17)

28524160 38794 90.74±1.12 0.0541 0.0624 0.3861 0.7170 0.6860

28549806 13148 86.90±1.41 -0.0121 0.0632 0.8477 0.9184 0.1288

28559497 3457 88.02±1.18 0.1233 0.0645 0.0560 0.2144 0.4011

28562142 812 79.55±5.08 0.0388 0.0211 0.0660 0.2144 2.2130

28562220 734 54.66±5.74 0.0185 0.0162 0.2528 0.5477 0.7468

28562685 269 8.48±2.67 0.1419 0.0596 0.0172 0.1121 2.6669

28562813 141 2.56±0.39 0.1754 0.2645 0.5072 0.7326 3.4526

28563054 -100 5.24±0.71 0.2564 0.0970 0.0082 0.1062 2.1579

28563089 -135 13.46±1.58 -0.0109 0.0466 0.8160 0.9184 0.1529

28563108 -154 1.92±0.22 -0.0850 0.3065 0.7816 0.9184 0.1602

28563119 -165 2.33±0.22 -0.3264 0.4351 0.4532 0.7326 1.3832

28564094 -1140 4.98±0.49 0.0106 0.1621 0.9479 0.9479 0.0220

28564117 -1163 5.77±0.74 0.1419 0.0934 0.1286 0.3345 0.3743

MAOA(ChrX)

43513914 -1553 39.69±4.26 -0.1017 0.0213 <0.0001 <0.0001 3.3041

43514189 -1278 41.85±3.59 -0.0707 0.0308 0.0218 0.0426 3.4065

43514483 -984 40.86±2.54 -0.0686 0.0269 0.0109 0.0305 3.3651

43514718 -749 48.87±3.30 -0.0361 0.0260 0.1651 0.2569 0.0159

43514740 -727 49.17±3.60 -0.0714 0.0196 0.0003 0.0013 4.5456

43515213 -254 18.76±5.10 0.0197 0.0185 0.2853 0.3994 0.0053

43515245 -222 40.31±5.95 0.0149 0.0177 0.3991 0.5079 0.5629

43515349 -118 37.03±4.01 -0.0584 0.0194 0.0026 0.0091 3.1218

43515377 -90 47.10±3.11 -0.0605 0.0269 0.0243 0.0426 4.6761

43515457 -10 56.55±2.00 0.0867 0.0384 0.0239 0.0426 2.8747

43515544 77 46.97±2.88 0.0107 0.0301 0.7232 0.7788 0.0387

43515575 108 46.38±2.27 -0.0056 0.0389 0.8852 0.8852 0.0441

43517029 1562 82.33±5.06 0.0085 0.0225 0.7072 0.7788 0.2659

43518105 2638 87.75±4.26 -0.0789 0.0197 0.0001 0.0004 5.6472

MAOB(ChrX)

43626076 115617 38.06±4.15 -0.0672 0.0188 0.0004 0.0029 4.2059

43738323 3370 83.50±4.04 0.0193 0.0382 0.6134 0.6260 0.0171

43739887 1806 81.62±3.26 0.0529 0.0281 0.0599 0.1197 1.3056

43741310 383 87.43±2.47 0.0474 0.0226 0.0361 0.0963 1.4085

43741376 317 18.36±4.76 0.0097 0.0200 0.6260 0.6260 0.0387

43741530 163 28.47±6.21 -0.0144 0.0174 0.4088 0.5451 3.4698

43741557 136 51.17±4.56 0.0383 0.0172 0.0259 0.0963 0.3055

43741601 92 17.49±5.36 0.0230 0.014 0.0988 0.1581 1.0579

* Adjusted for twin age, family income level, pack-year, alcohol consumption, physical activity, body mass index, and history of PTSD.

TSS: transcription start site.

Supplementary Table S5. Associations of specific types of childhood traumatic experiences with single CpG methylation of five stress-related genes in the THS

Genomic Relative Physical abuse Emotional abuse Sexual abuse General trauma Childhood trauma

position to TSS

(bp) β^* P^# q β^* P^# q β^* P^# q β^* P^# q β^* P^# q

BDNF (Chr11)

27743580 -1254 0.3880 0.176

2 0.251

7 -

0.1936 0.560

7 0.799

4 -

0.1446 0.723

6 0.808

7 -

0.0246 0.935

1 0.962

2 0.3821 0.188

9 0.377

7 27743583 -1257 -

0.1317 0.571

8 0.714

8 -

0.1693 0.546

6 0.799

4 -

0.1403 0.679

8 0.808

7 -

0.1727 0.482

0 0.854

2 -

0.0828 0.731

3 0.872

5 27743619 -1293 0.0728 0.675

3 0.750

3 -

0.2790 0.161

1 0.754

0 0.1051 0.675

1 0.808

7 -

0.1303 0.460

1 0.854

2 0.0461 0.785

3 0.872

5 27743642 -1316 0.6206 0.001

3 0.012

9 0.1074 0.639

5 0.799

4 0.4085 0.152

3 0.507

5 -

0.1799 0.368

6 0.854

2 0.3147 0.100

1 0.250

1 27743648 -1322 0.4438 0.010

5 0.038

1 0.3646 0.065

1 0.651

5 0.4066 0.103

2 0.507

5 0.1165 0.512

5 0.854

2 0.5280 0.001

6 0.015

9 27743651 -1325 0.4189 0.041

1 0.102

8 0.2090 0.383

4 0.799

4 0.5034 0.092

6 0.507

5 0.1090 0.604

7 0.863

9 0.4999 0.012

6 0.063

1 27743654 -1328 0.4841 0.135

3

0.225 6

- 0.2917

0.431 3

0.799 4

- 0.1626

0.727 8

0.808 7

- 0.0157

0.962 2

0.962

2 0.3530 0.264

6

0.440 9 27743664 -1338 -

0.8247 0.011

4 0.038

1 -

0.0608 0.870

9 0.962

1 0.4025 0.392

4 0.808

7 -

0.0272 0.935

3 0.962

2 0.3151 0.323

6 0.462

3 27743673 -1347 -

0.6687 0.062

4 0.124

8 -

0.5028 0.226

2 0.754

0 0.0616 0.905

5 0.905

5 -

0.3440 0.347

5 0.854

2 -

0.0292 0.933

7 0.933

7 27743679 -1353 0.0638 0.835

0

0.835 0

- 0.0165

0.962 1

0.962

1 0.2641 0.545

8

0.808

7 0.2773 0.371

4

0.854

2 0.6478 0.027

8

0.092 7 NR3C1 (Chr5)

14278352

8 -274 -

0.3530 0.153

0 0.333

0 -

0.1127 0.692

5 0.874

1 -

0.2225 0.535

2 0.867

5 0.4817 0.057

5 0.433

1 0.1576 0.518

6 0.617

4 14278353

1 -277 0.3631 0.202

6 0.337

6 0.3789 0.256

1 0.633

6 0.3163 0.450

9 0.842

3 0.5221 0.073

7 0.433

1 0.7157 0.010

5 0.087

4 14278353

7 -283 0.3808 0.181

1 0.335

8 0.1250 0.702

8 0.874

1 -

0.5763 0.161

7 0.808

3 0.5007 0.086

6 0.433

1 0.4003 0.153

2 0.307

3 14278354

0 -286 0.3841 0.252

4 0.371

2 0.5311 0.170

7 0.633

6 -

0.5154 0.290

0 0.842

3 0.1770 0.607

8 0.722

3 0.3591 0.277

7 0.408

4 14278354

7 -293 0.3911 0.159

9 0.333

0 0.8377 0.008

8 0.155

5 0.1608 0.693

0 0.867

5 0.4248 0.136

7 0.453

2 0.5060 0.065

1 0.203

5 14278356

6 -312 -

0.0023 0.992

8 0.992

8 0.4602 0.115

7 0.578

4 0.2034 0.582

5 0.867

5 0.3861 0.141

0 0.453

2 0.3951 0.115

4 0.307

3 14278356

9 -315 -

0.2195

0.369 7

0.486 5

- 0.3516

0.237 8

0.633

6 0.0848 0.818

6

0.867

5 0.2631 0.297

1

0.501 3

- 0.0891

0.716 6

0.779 0 14278358

4 -330 -

0.5297 0.146

4 0.333

0 0.0924 0.839

1 0.874

1 0.1177 0.832

8 0.867

5 0.3961 0.290

9 0.501

3 0.1973 0.590

2 0.670

7 14278360

7 -353 -

0.1616 0.559

0 0.636

5 -

0.0565 0.880

0 0.880

0 0.3134 0.471

7 0.842

3 0.3846 0.169

2 0.453

2 0.2878 0.299

4 0.415

8 14278362 -367 0.2584 0.585 0.636 - 0.548 0.830 - 0.816 0.867 0.4850 0.316 0.501 0.5368 0.246 0.384

1 5 5 0.3245 2 1 0.1582 4 5 0 3 1 6 14278362

7 -373 -

0.0560 0.822

9 0.857

2 -

0.1417 0.619

3 0.860

1 -

0.4144 0.247

9 0.842

3 -

0.1211 0.635

6 0.722

3 -

0.0404 0.868

8 0.868

8 14278363

7 -383 0.5923 0.042

7 0.152

6 0.2998 0.371

4 0.773

7 -

0.1074 0.799

7 0.867

5 0.0022 0.994

1 0.996

9 0.5662 0.047

8 0.170

9 14278363

9 -385 0.4530 0.188

0 0.335

8 0.2570 0.513

6 0.830

1 0.0748 0.880

2 0.880

2 0.3496 0.320

8 0.501

3 0.4757 0.157

6 0.307

3 14278365

5 -401 0.5207 0.041

2 0.152

6 0.4857 0.095

9 0.578

4 -

0.1004 0.785

8 0.867

5 0.4848 0.063

3 0.433

1 0.5890 0.018

0 0.090

0 14278366

3 -409 0.5326 0.050

7 0.158

6 0.0704 0.826

0 0.874

1 0.3937 0.328

3 0.842

3 0.2941 0.295

3 0.501

3 0.3705 0.169

6 0.307

3 14278367

8 -424 0.6490 0.039

1 0.152

6 0.2764 0.457

7 0.817

4 -

0.2307 0.621

3 0.867

5 -

0.2271 0.485

9 0.674

8 0.3055 0.329

9 0.434

1 14278368

5 -431 0.4510 0.010

7 0.066

8 0.2658 0.191

0 0.633

6 0.0994 0.698

6 0.867

5 0.1873 0.304

3 0.501

3 0.3814 0.028

4 0.118

3 14278368

8 -434 0.6293 0.004

0 0.033

7 0.5903 0.018

7 0.155

5 0.6474 0.041

1 0.515

7 0.3025 0.181

3 0.453

2 0.6181 0.003

9 0.087

4 14278370

2 -448 1.5668 0.000

0 0.001

1 0.3768 0.402

6 0.774

3 1.1657 0.041

3 0.515

7 0.5830 0.148

4 0.453

2 0.9390 0.014

1 0.088

3 14278371

2 -458 0.3013 0.270

6 0.375

9 0.1801 0.564

5 0.830

1 0.3646 0.355

3 0.842

3 0.0616 0.826

2 0.898

0 0.1990 0.457

8 0.572

2 14278371

6 -462 1.0220 0.003

0 0.033

7 0.4322 0.278

8 0.633

6 0.7730 0.126

6 0.791

4 0.3344 0.350

4 0.515

3 0.4454 0.193

3 0.322

1 14278373

0 -476 0.7927 0.124

0 0.333

0 0.1823 0.757

5 0.874

1 0.5867 0.429

7 0.842

3 1.0583 0.043

9 0.433

1 1.3382 0.007

4 0.087

4 14278373

5 -481 0.4910 0.392

8 0.491

0 0.7275 0.266

5 0.633

6 1.0038 0.224

3 0.842

3 0.3286 0.576

0 0.722

3 0.7729 0.168

3 0.307

3 14278374

2 -488 0.7802 0.228

6 0.357

1 1.7939 0.014

7 0.155

5 1.5381 0.103

5 0.791

4 -

0.3584 0.590

0 0.722

3 0.8692 0.172

1 0.307

3 14278374

4 -490 -

0.1794 0.580

1 0.636

5 0.0999 0.787

2 0.874

1 0.3407 0.464

6 0.842

3 0.0013 0.996

9 0.996

9 0.0608 0.848

2 0.868

8 SLC6A4 (Chr17)

28562957 -3 2.0855 0.055

7 0.209

3 -

0.3438 0.792

3 0.996

5 0.5368 0.741

2 0.986

2 1.3663 0.225

0 0.414

5 0.8700 0.422

9 0.734

4 28562970 -16 0.8051 0.173

3 0.209

3 -

0.0750 0.916

4 0.996

5 0.4945 0.576

1 0.986

2 0.7687 0.207

1 0.414

5 0.4690 0.426

1 0.734

4 28562974 -20 1.1596 0.140

1 0.209

3 0.0559 0.952

5 0.996

5 0.5922 0.612

4 0.986

2 0.7360 0.364

1 0.414

5 0.4471 0.567

2 0.734

4 28562986 -32 1.0643 0.172

2 0.209

3 -

0.0909 0.922

8 0.996

5 0.3097 0.790

1 0.986

2 0.9181 0.253

1 0.414

5 0.8561 0.269

2 0.734

4 28562991 -37 1.4241 0.135

1 0.209

3 0.0571 0.960

2 0.996

5 0.0708 0.960

3 0.986

2 0.9116 0.354

0 0.414

5 0.8968 0.344

0 0.734

4 28562993 -39 1.0524 0.121

3 0.209

3 -

0.2118 0.796

9 0.996

5 0.0502 0.960

7 0.986

2 0.9316 0.183

7 0.414

5 0.4722 0.486

3 0.734

4 28563002 -48 1.8473 0.153

0 0.209

3 -

0.3364 0.827

8 0.996

5 0.6586 0.732

1 0.986

2 1.8911 0.155

3 0.414

5 0.7661 0.551

1 0.734

4

28563016 -62 1.7426 0.125

2 0.209

3 0.0060 0.996

5 0.996

5 0.3598 0.832

0 0.986

2 1.9511 0.095

2 0.414

5 0.9964 0.378

2 0.734

4 28563020 -66 1.0346 0.177

9 0.209

3 0.0987 0.914

0 0.996

5 0.0197 0.986

2 0.986

2 0.7052 0.373

0 0.414

5 0.6396 0.401

0 0.734

4 28563054 -100 1.6248 0.087

7

0.209 3

- 0.1680

0.881 8

0.996

5 0.1664 0.906

2

0.986

2 1.0370 0.290

9

0.414

5 0.5048 0.593

2

0.734 4 28563089 -135 0.9322 0.143

2 0.209

3 0.0785 0.918

3 0.996

5 -

0.0767 0.935

7 0.986

2 0.2664 0.685

5 0.721

6 0.3107 0.624

2 0.734

4 28563101 -147 1.8179 0.138

0 0.209

3 0.3885 0.788

0 0.996

5 -

0.2296 0.899

0 0.986

2 1.8239 0.147

8 0.414

5 0.9916 0.413

3 0.734

4 28563106 -152 0.8964 0.113

1

0.209 3

- 0.0517

0.939 6

0.996

5 0.4767 0.573

4

0.986

2 0.7324 0.209

8

0.414

5 0.3258 0.563

9

0.734 4 28563108 -154 1.3808 0.093

6 0.209

3 0.6669 0.489

4 0.996

5 0.3500 0.772

5 0.986

2 1.0316 0.223

2 0.414

5 0.9809 0.226

8 0.734

4 28563119 -165 1.0489 0.116

4 0.209

3 0.1559 0.846

2 0.996

5 0.4978 0.617

9 0.986

2 0.6726 0.329

5 0.414

5 0.2890 0.664

3 0.738

1 28563138 -184 2.0406 0.017

3

0.209

3 0.1010 0.923

9

0.996

5 0.5973 0.645

3

0.986

2 1.0347 0.244

2

0.414

5 0.7376 0.392

5

0.734 4 28563143 -189 0.2098 0.858

4 0.858

4 -

0.5806 0.665

8 0.996

5 -

0.2410 0.886

9 0.986

2 0.2758 0.818

6 0.818

6 -

0.1329 0.907

7 0.907

7 28563159 -205 0.5326 0.338

4 0.376

0 0.3833 0.597

3 0.996

5 0.7483 0.381

7 0.986

2 0.5661 0.324

7 0.414

5 0.9177 0.097

8 0.734

4 28563174 -220 0.1690 0.590

9

0.622 0

- 0.4229

0.266 5

0.996 5

- 0.2111

0.653 8

0.986 2

- 0.4268

0.186 6

0.414 5

- 0.0920

0.769 1

0.809 5 28563185 -231 0.5915 0.050

0 0.209

3 0.4170 0.233

1 0.996

5 0.4385 0.320

8 0.986

2 0.3711 0.232

1 0.414

5 0.9400 0.001

2 0.023

4 MAOA (ChrX)

43515402 -65 0.3496 0.278

3 0.661

0 -

0.0215 0.954

3 0.954

3 -

0.2208 0.638

2 0.911

8 -

0.0067 0.983

7 0.983

7 0.1645 0.602

4 0.889

5 43515412 -55 0.1759 0.518

3 0.661

0 -

0.1660 0.609

6 0.954

3 -

0.1424 0.723

3 0.911

8 0.2510 0.367

1 0.514

0 0.1096 0.682

7 0.889

5 43515418 -49 0.2419 0.397

0

0.661

0 0.2760 0.416

4

0.954

3 0.0467 0.911

8

0.911

8 0.3923 0.178

1

0.514

0 0.2210 0.431

7

0.889 5 43515439 -28 0.2755 0.373

4 0.661

0 -

0.0747 0.837

5 0.954

3 -

0.0515 0.909

7 0.911

8 0.4308 0.172

2 0.514

0 0.3170 0.296

2 0.889

5 43515444 -23 0.1812 0.566

6 0.661

0 -

0.2099 0.572

2 0.954

3 -

0.2245 0.627

9 0.911

8 0.3024 0.348

6 0.514

0 0.0431 0.889

5 0.889

5 43515457 -10 0.4076 0.174

1

0.661

0 0.1863 0.601

9

0.954 3

- 0.1345

0.761 5

0.911

8 0.2859 0.351

9

0.514

0 0.2220 0.452

7

0.889 5

43515467 1 -

0.0245 0.941

0 0.941

0 0.1334 0.732

1 0.954

3 -

0.1274 0.792

7 0.911

8 0.1805 0.592

4 0.691

1 0.0799 0.805

5 0.889

5 MAOB (ChrX)

43741764 -71 0.9002 0.346

7 0.762

2 -

1.5762 0.162

8 0.613

0 1.9809 0.157

9 0.384

7 0.2445 0.804

0 0.984

3 0.7103 0.452

6 0.452

6 43741775 -82 0.9435 0.408

5 0.762

2 0.6619 0.624

9 0.983

4 1.1290 0.502

4 0.502

4 1.9921 0.088

5 0.619

8 3.8754 0.000

4 0.003

1

43741781 -88 0.0879 0.938

1 0.938

1 0.0281 0.983

4 0.983

4 3.3450 0.044

3 0.310

0 -

0.3250 0.780

3 0.984

3 1.5473 0.166

4 0.194

1 43741785 -92 1.0326 0.435

5 0.762

2 -

0.0780 0.960

9 0.983

4 2.4123 0.219

8 0.384

7 0.7613 0.577

1 0.984

3 2.8563 0.028

7 0.100

6 43741806 -113 0.7550 0.628

1

0.766

0 0.0899 0.961

2

0.983

4 3.0876 0.178

6

0.384

7 0.2574 0.872

5

0.984

3 2.5000 0.103

6

0.159 1 43741815 -122 1.5645 0.333

1 0.762

2 2.1267 0.256

1 0.613

0 2.3104 0.324

1 0.409

8 -

0.0327 0.984

3 0.984

3 2.5060 0.113

6 0.159

1 43741827 -134 0.5345 0.656

5 0.766

0 -

1.5907 0.262

7 0.613

0 1.6537 0.351

3 0.409

8 1.2341 0.317

7 0.984

3 2.3099 0.050

8 0.118

6

*Change in methylation level (%) for individuals with versus without the type of childhood traumatic experiences.

#Adjusted for twin age, family income level, pack-year, alcohol consumption, physical activity, body mass index, and history of PTSD.

TSS: transcription start site.

Supplementary Table S6. Associations of specific types of childhood traumatic experiences with single CpG methylation of five stress-related genes in the MMS

Genomic Relative Physical abuse Emotional abuse Sexual abuse General trauma Childhood trauma

position to TSS

(bp) β^* P^# q β^* P^# q β^* P^# q β^* P^# q β^* P^# q

BDNF (Chr11)

27679469 62857 -0.0952 0.3853 0.9227 0.1887 0.4821 0.8766 -0.1606 0.5756 0.8515 -

0.2851 0.3486 0.8384 -

0.2740 0.2147 0.7897 27679632 62694 -0.0595 0.2707 0.9269 -0.2812 0.1378 0.7782 0.2742 0.1631 0.5877 0.2468 0.2369 0.8347 -

0.0184 0.9047 0.9494 27679729 62597 0.6027 0.5294 0.8485 -0.2109 0.5707 0.9081 0.3367 0.3761 0.7026 0.9132 0.0204 0.4826 0.3704 0.2076 0.7897 27680480 61846 0.4554 0.4925 0.8785 0.6224 0.0678 0.7782 0.0056 0.9882 0.9905 0.2474 0.5336 0.8384 0.3411 0.2352 0.7897 27681475 60851 0.3079 0.3182 0.8785 0.2041 0.3595 0.8422 0.2150 0.3461 0.6971 0.3262 0.1771 0.8347 0.2400 0.1744 0.7897 27683959 58367 -0.0226 0.4881 0.9785 -0.1835 0.5871 0.9081 -0.3777 0.2626 0.6683 -

0.4643 0.1883 0.8347 -

0.4811 0.0633 0.6331 27695210 47116 -0.1458 0.3621 0.8991 -0.0277 0.9129 0.9566 0.3803 0.1551 0.5877 -

0.1002 0.7264 0.8741 0.1394 0.5034 0.8935 27696004 46322 0.0460 0.4312 0.9559 -0.2645 0.3796 0.8422 0.3970 0.2096 0.6020 0.2870 0.3945 0.8384 0.0805 0.7440 0.9331 27701991 40335 0.2091 0.3937 0.8834 -0.3478 0.2021 0.7782 -0.5158 0.0599 0.5026 0.0235 0.9365 0.9498 -

0.2483 0.2523 0.7897 27718978 23348 -1.0609 2.4191 0.8991 -1.8681 0.2584 0.8321 -3.2734 0.0429 0.4356 -

1.7081 0.3050 0.8384 -

2.6464 0.0297 0.6013 27720709 21617 -0.0785 0.1747 0.8991 -0.0652 0.5922 0.9081 0.1902 0.1466 0.5877 -

0.1351 0.3341 0.8384 0.0072 0.9436 0.9494 27721088 21238 0.2535 0.3948 0.8823 -0.1974 0.4738 0.8766 -0.1153 0.6980 0.9170 0.3945 0.2094 0.8347 0.2403 0.2950 0.8116 27721222 21104 -0.7450 0.3831 0.8029 -0.1020 0.7098 0.9149 0.2352 0.4074 0.7404 -

0.1887 0.5309 0.8384 0.0518 0.8148 0.9331 27721270 21056 0.2470 0.1471 0.8485 -0.0324 0.7560 0.9149 -0.0386 0.7226 0.9170 -

0.1230 0.2822 0.8347 -

0.0216 0.7983 0.9331 27721277 21049 -0.0027 0.1014 0.9785 -0.1700 0.0125 0.7782 0.0434 0.5591 0.8446 -

0.1129 0.1495 0.8347 -

0.0558 0.3314 0.8704 27721280 21046 0.9447 0.4407 0.8029 0.0546 0.8645 0.9566 -0.0583 0.8650 0.9748 -

0.4333 0.2311 0.8347 -

0.0312 0.9063 0.9494 27721350 20976 0.1251 0.3289 0.8991 -0.3393 0.1355 0.7782 0.0902 0.7165 0.9170 0.1850 0.4829 0.8384 -

0.1154 0.5471 0.9228 27721668 20658 -0.1775 0.2837 0.8823 -0.0864 0.6636 0.9149 0.2375 0.2683 0.6683 0.0830 0.7163 0.8741 0.0680 0.6821 0.9331 27722037 20289 -0.1164 0.1996 0.8823 -0.0232 0.8681 0.9566 0.0437 0.7636 0.9456 -

0.1991 0.1903 0.8347 0.0098 0.9306 0.9494 27722060 20266 0.1436 0.3048 0.8991 -0.0112 0.9579 0.9768 0.4640 0.0389 0.4356 0.0458 0.8505 0.9498 0.2624 0.1335 0.7897 27722063 20263 -0.2847 0.2519 0.8485 -0.0373 0.8326 0.9566 -0.0263 0.8861 0.9830 0.0376 0.8466 0.9498 -

0.0922 0.5171 0.8955 27722066 20260 0.1618 0.1005 0.8485 -0.0328 0.6449 0.9149 -0.1607 0.0220 0.3899 -

0.0088 0.9074 0.9498 -

0.0396 0.4778 0.8927 27722523 19803 -0.0687 0.1039 0.8823 -0.0250 0.7304 0.9149 0.0222 0.7783 0.9456 - 0.0000 0.0027 - 0.0464 0.6013

0.3218 0.1190 27722549 19777 0.0409 0.0546 0.8823 0.0487 0.2031 0.7782 0.0005 0.9905 0.9905 -

0.0535 0.2114 0.8347 0.0241 0.4420 0.8704 27722617 19709 0.1892 0.3159 0.8823 0.1115 0.6127 0.9081 -0.0972 0.6658 0.9121 0.1313 0.5803 0.8384 0.0979 0.5763 0.9300 27722620 19706 0.2272 0.3222 0.8823 0.2368 0.2918 0.8422 0.3173 0.1720 0.5877 -

0.4863 0.0439 0.6229 0.0193 0.9152 0.9494 27722636 19690 -0.1749 0.2213 0.8823 -0.1909 0.2147 0.7782 -0.2743 0.0849 0.5026 -

0.2054 0.2248 0.8347 -

0.2724 0.0260 0.6013 27722638 19688 0.2124 0.2381 0.8789 0.0700 0.6740 0.9149 -0.2559 0.1458 0.5877 0.2390 0.2020 0.8347 0.1036 0.4503 0.8704 27722722 19604 -0.2646 0.3977 0.8823 -0.0848 0.7603 0.9149 -0.6788 0.0188 0.3899 -

0.6418 0.0370 0.6229 -

0.5697 0.0108 0.6013 27722774 19552 0.5315 0.1832 0.3672 0.1792 0.1848 0.7782 0.0295 0.8418 0.9748 0.0762 0.6267 0.8395 0.2031 0.0713 0.6331 27722889 19437 -0.1206 0.3266 0.8991 0.1635 0.4718 0.8766 -0.3095 0.2077 0.6020 -

0.1179 0.6529 0.8499 -

0.0471 0.8048 0.9331 27722971 19355 -0.2643 0.2243 0.8485 0.0547 0.7282 0.9149 0.1381 0.4171 0.7404 -

0.1976 0.2736 0.8347 -

0.0882 0.5023 0.8935 27723075 19251 0.1914 0.1469 0.8485 0.0048 0.9631 0.9768 -0.0751 0.5033 0.8122 -

0.1312 0.2710 0.8347 -

0.0792 0.3604 0.8704 27723128 19198 0.1980 0.0881 0.8029 -0.1156 0.0709 0.7782 -0.0490 0.4689 0.7927 0.0362 0.6140 0.8384 0.0137 0.7941 0.9331 27723190 19136 0.0680 0.0838 0.8823 0.0331 0.5728 0.9081 -0.0881 0.1610 0.5877 0.0089 0.8948 0.9498 0.0221 0.6506 0.9331 27723214 19112 0.1413 0.2483 0.8823 0.2087 0.2257 0.7782 -0.0797 0.6680 0.9121 -

0.0104 0.9580 0.9580 0.1189 0.4064 0.8704 27723218 19108 -0.0533 0.3988 0.9482 -0.5166 0.0582 0.7782 -0.5046 0.0767 0.5026 0.1806 0.5556 0.8384 -

0.3230 0.1478 0.7897 27723237 19089 0.0055 0.1308 0.9785 -0.1330 0.1397 0.7782 -0.0074 0.9369 0.9853 -

0.0888 0.3692 0.8384 -

0.0758 0.2972 0.8116 27723245 19081 0.0297 0.1924 0.9482 0.0626 0.6419 0.9149 0.1477 0.2971 0.6683 -

0.4541 0.0017 0.0620 -

0.1252 0.2536 0.7897 27723290 19036 0.4126 0.5704 0.8823 -0.0522 0.8960 0.9566 -0.7228 0.0756 0.5026 0.1803 0.6799 0.8620 -

0.1151 0.7198 0.9331 27723385 18941 0.5303 0.3665 0.8485 0.2564 0.3190 0.8422 0.0681 0.8050 0.9526 -

0.0243 0.9339 0.9498 0.2523 0.2352 0.7897 27723409 18917 -0.3335 0.1909 0.8485 0.2028 0.1330 0.7782 0.1994 0.1529 0.5877 -

0.0982 0.5086 0.8384 0.0821 0.4536 0.8704 27732958 9368 0.1899 0.5863 0.8991 0.0522 0.8982 0.9566 0.4396 0.2879 0.6683 0.2598 0.5520 0.8384 0.2778 0.3885 0.8704 27739827 2499 -0.2108 0.7746 0.9227 -1.0973 0.0380 0.7782 -0.0386 0.9436 0.9853 0.2123 0.7124 0.8741 -

0.0833 0.8442 0.9494 27740078 2248 -0.2190 0.4045 0.8834 -0.1428 0.6139 0.9081 -0.3142 0.2873 0.6683 0.4164 0.1829 0.8347 0.0918 0.6902 0.9331 27740161 2165 0.2069 0.1539 0.8485 0.0633 0.5642 0.9081 -0.1545 0.1780 0.5877 -

0.0127 0.9176 0.9498 0.0289 0.7466 0.9331 27740495 1831 0.4596 0.2349 0.8029 -0.2188 0.1899 0.7782 -0.4436 0.0095 0.3899 0.0824 0.6583 0.8499 -

0.2623 0.0508 0.6013 27740813 1513 -0.0800 0.1953 0.8991 -0.0143 0.9162 0.9566 0.0729 0.6172 0.8943 0.0428 0.7822 0.9105 0.0658 0.5589 0.9228 27740876 1450 -0.1171 0.1590 0.8823 0.0142 0.8982 0.9566 0.2541 0.0186 0.3899 - 0.2531 0.8347 0.1124 0.1917 0.7897

0.1317 27741077 1249 0.2143 0.2224 0.8785 -0.1396 0.3689 0.8422 -0.0075 0.9635 0.9905 -

0.0939 0.5869 0.8384 -

0.1038 0.4111 0.8704 27741916 410 -0.2237 0.3215 0.8823 0.3021 0.1764 0.7782 0.2174 0.3547 0.6971 -

0.1578 0.5274 0.8384 0.0747 0.6828 0.9331 27742060 266 -0.5081 0.8856 0.8823 -0.2049 0.7411 0.9149 -0.2861 0.6598 0.9121 0.6106 0.3749 0.8384 0.1468 0.7710 0.9331 27742138 188 -0.3320 0.2523 0.8485 0.0241 0.8922 0.9566 -0.1320 0.4935 0.8122 -

0.2689 0.1871 0.8347 -

0.1592 0.2833 0.8116 27742219 107 -0.0970 0.3700 0.9227 0.3062 0.2302 0.7782 0.3557 0.1821 0.5877 -

0.2304 0.4172 0.8384 0.2952 0.1535 0.7897 27742355 -29 0.3684 0.3969 0.8785 0.3589 0.1945 0.7782 0.3539 0.2120 0.6020 -

0.5019 0.0885 0.8347 0.1715 0.4385 0.8704 27742365 -39 -0.2603 0.2967 0.8789 0.1988 0.3354 0.8422 -0.0569 0.7857 0.9456 -

0.3032 0.1655 0.8347 -

0.0105 0.9487 0.9494 27742369 -43 -0.9625 0.8431 0.8485 0.5909 0.3130 0.8422 0.0550 0.9221 0.9853 -

0.2993 0.6035 0.8384 0.4083 0.3532 0.8704 27742435 -109 -0.8003 2.2576 0.8991 1.0924 0.4869 0.8766 -1.6663 0.3012 0.6683 1.4685 0.3869 0.8384 0.1050 0.9333 0.9494 27742454 -128 2.6067 2.1339 0.8485 1.6437 0.2695 0.8321 0.9215 0.5405 0.8343 1.3547 0.3954 0.8384 1.8897 0.1042 0.7897 27742832 -506 -0.9668 2.9375 0.8991 1.8162 0.3697 0.8422 -3.5442 0.0803 0.5026 0.2044 0.9239 0.9498 -

0.7145 0.6511 0.9331 27743258 -932 -0.1948 0.1854 0.8593 0.0420 0.7472 0.9149 0.0112 0.9365 0.9853 -

0.0230 0.8783 0.9498 -

0.0069 0.9494 0.9494 27743348 -1022 -0.3508 0.2260 0.8485 -0.1038 0.5155 0.8927 0.1060 0.5273 0.8319 -

0.1392 0.4329 0.8384 -

0.0530 0.6839 0.9331 27743580 -1254 -1.7994 1.2693 0.8485 1.1437 0.1992 0.7782 -0.8650 0.3446 0.6971 -

0.5013 0.6008 0.8384 -

1.0199 0.1480 0.7897 27743619 -1293 -0.4254 0.3903 0.8593 -0.2309 0.3928 0.8450 -0.2958 0.2719 0.6683 -

0.4995 0.0656 0.7768 -

0.4214 0.0369 0.6013 27743664 -1338 0.2538 0.1715 0.8485 -0.0960 0.4284 0.8691 -0.1964 0.1066 0.5821 -

0.0777 0.5524 0.8384 -

0.1099 0.2504 0.7897 27744049 -1723 -0.0963 0.7247 0.9482 0.6163 0.2192 0.7782 -0.0921 0.8586 0.9748 -

0.5030 0.3515 0.8384 -

0.1700 0.6715 0.9331 27744363 -2037 0.7676 0.4232 0.8485 0.2472 0.4190 0.8691 -0.6550 0.0420 0.4356 -

0.1059 0.7604 0.8998 -

0.0744 0.7687 0.9331 27744490 -2164 0.1071 0.0846 0.8485 -0.0547 0.3541 0.8422 -0.0569 0.3633 0.6971 -

0.0394 0.5531 0.8384 -

0.0396 0.4147 0.8704 27744557 -2231 -0.3887 0.3738 0.8593 -0.5553 0.0310 0.7782 0.2618 0.3233 0.6955 0.2263 0.4198 0.8384 0.0607 0.7698 0.9331 27744675 -2349 0.3953 0.8238 0.8991 -0.3917 0.4939 0.8766 0.2062 0.7233 0.9170 0.4181 0.4964 0.8384 0.1887 0.6766 0.9331 27744759 -2433 -0.1415 0.6784 0.9269 -0.0088 0.9851 0.9851 -0.3513 0.4604 0.7927 0.3820 0.4425 0.8384 0.4115 0.2558 0.7897 NR3C1 (Chr5)

14265882

8 124426 0.0826 0.2272 0.9730 -0.0877 0.5819 0.7911 0.0536 0.7496 0.8968 0.2240 0.2064 0.5444 0.1170 0.3670 0.8350 14269296

1 90293 -0.2994 0.4328 0.9730 -0.5262 0.0824 0.3767 0.1337 0.6834 0.8968 0.6586 0.0551 0.2939 0.1942 0.4418 0.8350

14272991

3 53341 0.1852 0.9864 0.9730 0.9182 0.1730 0.4986 -0.3633 0.5908 0.8968 0.3731 0.5982 0.8202 0.3373 0.5207 0.8350 14274031

4 42940 0.0329 0.3845 0.9730 -0.6188 0.0200 0.1596 -0.8052 0.0027 0.0874 0.3628 0.2120 0.5444 -

0.3768 0.0774 0.8252 14275701

1 26243 -0.0863 0.3286 0.9730 -0.5541 0.0131 0.1397 -0.2842 0.2496 0.8968 0.2522 0.3372 0.6348 -

0.1517 0.4273 0.8350 14275731

2 25942 -0.2229 0.3514 0.9730 0.2498 0.3031 0.6003 0.2002 0.4350 0.8968 0.1078 0.6921 0.8202 0.0043 0.9828 0.9897 14277627

4 6980 1.0783 1.4093 0.9730 -0.8207 0.3928 0.6518 0.0003 0.9998 0.9998 0.4061 0.6834 0.8202 -

0.4897 0.5061 0.8350 14278025

4 3000 0.0526 0.2276 0.9730 0.1515 0.3377 0.6003 -0.1631 0.3408 0.8968 0.4897 0.0057 0.1362 0.1975 0.1330 0.8350 14278069

3 2561 0.1443 0.4440 0.9730 -0.7589 0.0115 0.1397 -0.1927 0.5374 0.8968 0.4322 0.1890 0.5444 -

0.2954 0.2202 0.8350 14278149

8 1756 -0.2264 1.9608 0.9730 -0.1584 0.9067 0.9671 0.7428 0.5781 0.8968 0.8952 0.5200 0.7924 -

0.1041 0.9204 0.9897 14278172

3 1531 -0.5811 0.6032 0.9730 0.6815 0.1119 0.4266 0.5034 0.2618 0.8968 -

0.5416 0.2552 0.5444 0.2567 0.4609 0.8350 14278173

6 1518 0.2848 0.7050 0.9730 1.5613 0.0013 0.0417 0.2440 0.6390 0.8968 -

0.6973 0.2038 0.5444 0.2488 0.5367 0.8350 14278207

2 1182 0.2167 0.1641 0.9730 -0.0537 0.6428 0.7911 -0.1197 0.3392 0.8968 -

0.0016 0.9902 0.9902 -

0.0569 0.5568 0.8350 14278279

1 463 -0.3444 0.2515 0.9730 -0.2091 0.2381 0.5443 -0.0121 0.9495 0.9998 -

0.2180 0.2785 0.5571 -

0.0889 0.5463 0.8350 14278282

7 427 0.0371 0.2378 0.9730 0.0779 0.6387 0.7911 0.1153 0.5062 0.8968 -

0.0998 0.5867 0.8202 0.0378 0.7791 0.9897 14278362

1 -367 -0.0463 0.2600 0.9730 -0.0479 0.7916 0.9047 -0.0691 0.7248 0.8968 -

0.4097 0.0474 0.2939 -

0.0981 0.5169 0.8350 14278363

9 -385 -0.0084 0.0851 0.9730 -0.0581 0.3271 0.6003 -0.0326 0.6048 0.8968 0.0280 0.6759 0.8202 -

0.0074 0.8802 0.9897 14278384

3 -589 0.0019 0.0569 0.9730 -0.0326 0.4094 0.6518 -0.0111 0.7951 0.9087 0.0091 0.8427 0.9280 0.0016 0.9604 0.9897 14278422

2 -968 -0.0305 0.1714 0.9730 0.0090 0.9400 0.9704 -0.0822 0.4960 0.8968 0.0231 0.8568 0.9280 0.0012 0.9897 0.9897 14278432

3 -1069 -0.0315 0.2387 0.9730 -0.0371 0.8231 0.9082 0.0896 0.5961 0.8968 -

0.0754 0.6712 0.8202 -

0.0273 0.8354 0.9897 14278438

2 -1128 -0.1819 0.2470 0.9730 -0.1184 0.4925 0.7164 -0.1049 0.5749 0.8968 -

0.1514 0.4458 0.7133 -

0.2575 0.0719 0.8252 14278446

2 -1208 0.0040 0.0648 0.9730 -0.0554 0.2141 0.5270 -0.0520 0.2810 0.8968 -

0.0467 0.3629 0.6451 -

0.0685 0.0637 0.8252 14278452

2 -1268 -0.2489 0.1926 0.9730 0.0715 0.5975 0.7911 -0.0510 0.7143 0.8968 -

0.1712 0.2405 0.5444 -

0.0917 0.3939 0.8350 14278472

1 -1467 0.5482 0.3764 0.9730 0.0724 0.7855 0.9047 -0.3240 0.2277 0.8968 0.5581 0.0475 0.2939 0.1176 0.5741 0.8350 14278498

2 -1728 -0.0666 0.0873 0.9730 -0.0940 0.1200 0.4266 0.0679 0.3032 0.8968 -

0.1356 0.0502 0.2939 -

0.0521 0.3055 0.8350 14278517 -1918 -0.0405 0.0928 0.9730 0.0004 0.9947 0.9947 0.0092 0.8932 0.9856 - 0.0085 0.1362 - 0.2061 0.8350

2 0.1856 0.0667 14278525

8 -2004 -1.1508 0.3705 0.0980 -0.2194 0.4278 0.6518 -0.0932 0.7567 0.8968 -

0.2583 0.4188 0.7053 -

0.1314 0.5711 0.8350 14278640

5 -3151 -0.2929 0.3079 0.9730 -0.3859 0.0733 0.3767 0.0051 0.9820 0.9998 0.3726 0.1143 0.5223 -

0.0303 0.8627 0.9897 14278877

6 -5522 -0.0104 0.2160 0.9730 -0.2117 0.1575 0.4986 -0.1070 0.4893 0.8968 0.1913 0.2401 0.5444 -

0.0510 0.6711 0.9337 14281482

7 -31573 0.1264 0.2023 0.9730 0.1375 0.3314 0.6003 0.1330 0.3714 0.8968 0.0259 0.8700 0.9280 0.0999 0.3861 0.8350 14281546

3 -32209 -0.3099 0.3106 0.9730 -0.4617 0.0343 0.2193 -0.3707 0.1131 0.8968 0.3124 0.2120 0.5444 -

0.2305 0.2034 0.8350 14281546

9 -32215 -0.1416 0.5896 0.9730 -0.5434 0.1870 0.4986 0.7726 0.0702 0.8968 0.0232 0.9596 0.9902 0.1282 0.7022 0.9363 SLC6A4 (Chr17)

28524160 38794 0.4113 0.5259 0.7640 0.7840 0.0296 0.2618 0.1931 0.6162 0.8828 0.3505 0.3881 0.5607 0.1898 0.5247 0.9133 28549806 13148 -1.3272 0.5617 0.2818 -0.4046 0.3203 0.6940 0.0206 0.9623 0.9623 -

1.0601 0.0190 0.1552 -

0.6690 0.0435 0.5084 28559497 3457 0.1934 0.5508 0.7873 -0.4090 0.2847 0.6940 -0.1721 0.6791 0.8828 0.6124 0.1629 0.3705 -

0.1989 0.5352 0.9133 28562142 812 1.2916 2.1100 0.7843 0.8711 0.5473 0.7430 -3.0462 0.0266 0.3019 2.6544 0.0765 0.3314 -

0.4589 0.6761 0.9133 28562220 734 0.2884 2.5498 0.9103 -0.8645 0.6243 0.7430 -3.3105 0.0547 0.3019 4.0713 0.0239 0.1552 0.2246 0.8700 0.9133 28562685 269 -0.8252 0.6638 0.5696 -0.6580 0.1556 0.6745 0.6177 0.1972 0.5619 0.0075 0.9883 0.9883 0.0519 0.8900 0.9133 28562813 141 -0.1969 0.1585 0.5696 0.0878 0.4292 0.7430 0.1999 0.0697 0.3019 -

0.0174 0.8830 0.9883 0.1356 0.1173 0.5084 28563054 -100 0.2463 0.3388 0.7640 -0.1147 0.6287 0.7430 0.1114 0.6542 0.8828 0.1979 0.4517 0.5872 0.1554 0.4194 0.9133 28563089 -135 1.2035 0.7501 0.5696 -0.2956 0.5788 0.7430 0.6322 0.2593 0.5619 -

0.8148 0.1697 0.3705 0.1724 0.6927 0.9133 28563108 -154 0.1386 0.1058 0.5696 0.0179 0.8114 0.8790 0.0239 0.7678 0.9074 0.0072 0.9337 0.9883 0.0068 0.9133 0.9133 28563119 -165 0.0398 0.0986 0.7873 -0.1385 0.0403 0.2618 0.0115 0.8709 0.9435 0.0944 0.1995 0.3705 -

0.0154 0.7793 0.9133 28564094 -1140 -0.1759 0.2262 0.7640 -0.0030 0.9850 0.9850 -0.1058 0.5137 0.8828 -

0.2225 0.1910 0.3705 -

0.2091 0.0917 0.5084 28564117 -1163 0.1327 0.3528 0.7873 0.2716 0.2757 0.6940 0.3068 0.2415 0.5619 -

0.2892 0.2996 0.4868 0.1233 0.5444 0.9133 MAOA (ChrX)

43513914 -1553 2.0779 1.9542 0.6822 0.1838 0.8939 0.8939 -3.0994 0.0298 0.2134 1.9681 0.1999 0.9005 -

1.5075 0.1783 0.6136 43514189 -1278 0.6965 1.2471 0.9371 -0.2441 0.7697 0.8808 0.5523 0.4908 0.7450 0.3741 0.6526 0.9063 -

0.1332 0.8307 0.8946 43514483 -984 -1.4342 1.1091 0.6822 -1.2212 0.1151 0.6473 -0.7020 0.4068 0.7450 -

0.8682 0.3339 0.9005 -

1.5569 0.0155 0.2176 43514718 -749 -0.5607 1.3966 0.9371 -0.7654 0.4247 0.7204 0.4983 0.6019 0.7450 0.8724 0.3859 0.9005 -

0.3262 0.6584 0.8946

43514740 -727 -2.4667 1.5847 0.6822 -1.2237 0.2746 0.7204 -2.3896 0.0465 0.2134 0.8452 0.5137 0.9063 -

1.5905 0.0873 0.4076 43515213 -254 -0.1821 2.2235 0.9371 0.3506 0.8179 0.8808 2.6958 0.0677 0.2134 -

2.5344 0.1108 0.7757 -

0.3303 0.7778 0.8946 43515245 -222 -2.9911 2.6085 0.6822 -1.6184 0.3751 0.7204 0.9215 0.6164 0.7450 -

0.5505 0.7768 0.9063 -

0.1583 0.9122 0.9122 43515349 -118 -0.2425 1.7716 0.9371 1.7986 0.1387 0.6473 -0.0723 0.9561 0.9561 -

0.1414 0.9192 0.9745 0.2225 0.8267 0.8946 43515377 -90 -3.6848 1.4025 0.1529 -2.8389 0.0045 0.0624 -0.5351 0.6103 0.7450 -

0.4831 0.6618 0.9063 -

1.6664 0.0378 0.2645 43515457 -10 -1.3759 0.9546 0.6822 -0.4983 0.4631 0.7204 -0.3317 0.6386 0.7450 0.6790 0.3624 0.9005 -

0.3591 0.5120 0.8946 43515544 77 -0.2084 1.3080 0.9371 -0.8369 0.3586 0.7204 -1.7210 0.0629 0.2134 2.3897 0.0139 0.1952 -

0.3517 0.6300 0.8946 43515575 108 -0.9036 1.0641 0.7985 -0.4651 0.5331 0.7463 1.3456 0.0762 0.2134 -

0.2767 0.7348 0.9063 0.4550 0.4468 0.8946 43517029 1562 -0.1537 1.9396 0.9371 -0.4480 0.7396 0.8808 0.4514 0.7411 0.7982 0.0460 0.9745 0.9745 0.6209 0.5582 0.8946 43518105 2638 0.2030 2.0332 0.9371 1.4216 0.3138 0.7204 -1.2398 0.3960 0.7450 -

0.5425 0.7240 0.9063 -

1.3853 0.2191 0.6136 MAOB (ChrX)

43626076 115617 0.9165 1.9833 0.8612 2.5082 0.0656 0.4882 -2.5745 0.0732 0.3438 -

2.0515 0.1807 0.5396 -

1.4123 0.2085 0.8896 43738323 3370 0.9329 1.0867 0.8612 1.0044 0.1831 0.4882 -1.0272 0.1703 0.3719 0.7718 0.3373 0.6168 -

0.1918 0.7454 0.9805 43739887 1806 -0.0795 1.4305 0.9559 0.0738 0.9402 0.9402 -1.6280 0.0859 0.3438 1.2867 0.2023 0.5396 0.1037 0.8907 0.9805 43741310 383 0.3250 1.8040 0.9559 0.3634 0.7701 0.9402 0.3266 0.7900 0.7921 1.1185 0.3855 0.6168 0.0374 0.9687 0.9805 43741376 317 -2.3271 1.9372 0.8612 -0.2600 0.8491 0.9402 1.8255 0.1859 0.3719 -

0.6065 0.6821 0.8010 0.0266 0.9805 0.9805 43741530 163 1.1673 2.1713 0.8612 0.3013 0.8421 0.9402 0.4037 0.7921 0.7921 -

0.4066 0.8010 0.8010 0.1265 0.9155 0.9805 43741557 136 1.8170 2.5352 0.8612 2.5412 0.1443 0.4882 -1.0334 0.5522 0.7921 4.2906 0.0191 0.1526 1.6414 0.2224 0.8896 43741601 92 -2.2274 2.5679 0.8612 -1.5302 0.3931 0.7862 -0.7778 0.6699 0.7921 0.5486 0.7748 0.8010 -

0.8064 0.5694 0.9805

*Change in DNA methylation level (%) for individuals with versus without the type of childhood traumatic experiences.

#Adjusted for twin age, family income level, pack-year, alcohol consumption, physical activity, body mass index, and history of PTSD.

TSS: transcription start site.