ARTICLE TITLE: DNA methylation signatures of peripheral

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ARTICLE TITLE: DNA methylation signatures of peripheral leukocytes in schizophrenia
JOURNAL NAME: NeuroMolecular Medicine
Makoto Kinoshita1,6, Shusuke Numata1,6, Atsushi Tajima2, Shinji Shimodera3, Shinji Ono4, Akira Imamura4,
Jun-ichi Iga1, Shinya Watanabe1, Kumiko Kikuchi1, Hiroko Kubo1, Masahito Nakataki1, Satsuki Sumitani1,
Issei Imoto2, Yuji Okazaki5, Tetsuro Ohmori1
1
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health
Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
2
Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate
School, Tokushima, Japan
3
Department of Neuropsychiatry, Kochi Medical School, Kochi, Japan
4
Department of Neuropsychiatry, Nagasaki University Graduate School of Biomedical Science, Nagasaki,
Japan
5
Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan
6
These authors contributed equally to this work.
Corresponding author: Shusuke Numata
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health
Biosciences, The University of Tokushima Graduate School
3-8-15 Kuramoto-cho Tokushima 770-8503, Japan
TEL: 81-886-33-7130,
FAX: 81-886-33-7131
E-mail address: shu-numata@umin.ac.jp
Supplementary table S5. 153 CpG sites located in the CGIs and in the regions flanking CGIs. *Positions
refer to Genome Research Consortium human genome build 37 (GRCh37)/UCSC human genome 19 (hg19)
Probe ID
UCSC RefGene
Chromosome
Position*
name
UCSC
Relation to
RefGene
UCSC CpG
group
island
First set of samples
Second set of samples
FDR
Mean
Uncorrected
Mean
corrected
beta
p-value
beta
p-value
difference
difference
cg06515617
-
8
788006
intergenic
CGI shore
2.40.E-06
1.19.E-01
4.20.E-02
1.48.E-02
cg26642667
SND1
7
127292389
promoter
CGI
3.41.E-06
9.03.E-10
8.16.E-04
-2.84.E-02
cg22406758
-
11
631684
intergenic
CGI shelf
3.41.E-06
5.77.E-02
1.31.E-02
1.40.E-02
cg09050761
-
8
17272669
intergenic
CGI shore
5.09.E-06
1.15.E-01
2.18.E-02
1.10.E-02
cg05610699
POM121
7
72349222
promoter
CGI shore
2.21.E-05
4.91.E-02
7.60.E-03
1.12.E-02
cg21185154
CAMSAP1
9
138796683
gene body
CGI shore
2.60.E-05
6.44.E-02
2.75.E-03
1.20.E-02
cg08739385
EPHA10
1
38201818
gene body
CGI shore
6.46.E-05
1.23.E-01
4.57.E-02
2.47.E-02
cg06882504
TM2D1
1
62188229
gene body
CGI shelf
7.62.E-05
6.21.E-02
1.97.E-02
2.20.E-02
cg19027884
-
7
130414263
intergenic
CGI shelf
1.04.E-04
6.99.E-02
5.39.E-03
1.61.E-02
cg23826579
MICA
6
31373932
gene body
CGI shelf
1.39.E-04
8.90.E-02
2.63.E-02
1.90.E-02
cg24714100
HCG18
6
30290603
gene body
CGI shelf
1.44.E-04
1.30.E-01
2.83.E-02
3.29.E-02
cg04948956
-
12
15945752
intergenic
CGI shelf
1.98.E-04
1.21.E-01
1.13.E-02
4.73.E-02
cg14846244
-
12
27861039
intergenic
CGI shelf
2.90.E-04
1.12.E-01
1.21.E-03
1.35.E-02
cg26383537
CCDC97
19
41817029
gene body
CGI shore
4.57.E-04
9.55.E-02
2.31.E-02
5.31.E-02
cg11763017
-
2
11608817
intergenic
CGI shelf
7.69.E-04
6.27.E-02
3.85.E-02
1.60.E-02
cg10970409
VIPR1
3
42543566
promoter
CGI
9.06.E-04
1.90.E-02
9.24.E-03
1.16.E-02
cg10302200
-
17
80303530
intergenic
CGI
9.44.E-04
2.60.E-02
1.94.E-02
1.63.E-02
cg19484299
MSL3L2
2
234775274
gene body
CGI shore
1.01.E-03
2.31.E-02
3.39.E-02
2.22.E-02
cg04343242
BDH2
4
104000066
3'UTR
CGI shelf
1.45.E-03
1.29.E-01
1.59.E-03
2.95.E-02
cg24069815
PRPF39
14
45557069
promoter
CGI shelf
1.62.E-03
6.13.E-02
1.89.E-02
1.04.E-02
cg09767616
ZNF530
19
58115732
gene body
CGI shelf
1.68.E-03
1.38.E-02
3.28.E-02
1.96.E-02
cg04676172
LEMD2
6
33757040
promoter
CGI shore
1.93.E-03
9.53.E-03
7.82.E-03
1.32.E-02
cg23044647
MTMR14
3
9691127
promoter
CGI
1.96.E-03
1.31.E-02
1.57.E-02
1.50.E-02
cg13905333
-
9
134186060
intergenic
CGI shelf
1.96.E-03
4.45.E-02
1.00.E-02
1.27.E-02
cg26153954
APP
21
27543721
promoter
CGI shore
2.08.E-03
1.01.E-01
2.17.E-02
3.32.E-02
cg04195527
INSIG2
2
118846289
promoter
CGI shore
2.31.E-03
4.88.E-06
2.56.E-02
-1.77.E-02
cg04930919
-
15
84748862
intergenic
CGI
2.76.E-03
2.34.E-02
3.15.E-02
5.20.E-02
cg04442576
SLC35F1
6
118228650
promoter
CGI
3.31.E-03
1.01.E-08
3.61.E-02
-1.76.E-02
cg16497340
-
5
180601183
intergenic
CGI shelf
3.39.E-03
2.11.E-02
3.27.E-02
2.95.E-02
cg10641615
HOTAIR
12
54359797
gene body
CGI
3.49.E-03
4.38.E-05
3.88.E-02
-1.69.E-02
cg07801516
ZNF461
19
37154552
gene body
CGI shelf
3.58.E-03
5.62.E-02
2.73.E-02
1.41.E-02
cg01795082
ATP11A
13
113536797
3'UTR
CGI shore
3.94.E-03
2.64.E-02
2.83.E-02
2.45.E-02
cg04145949
ZNF845
19
53837361
promoter
CGI
3.97.E-03
1.62.E-07
1.18.E-02
-1.51.E-02
cg21140633
-
17
15600659
intergenic
CGI shelf
3.97.E-03
4.21.E-02
4.61.E-02
1.11.E-02
cg10093594
MAPKAPK2
1
206858754
promoter
CGI
4.08.E-03
2.69.E-02
3.20.E-02
2.15.E-02
cg02850401
-
12
133178636
intergenic
CGI
4.32.E-03
2.31.E-02
1.29.E-02
1.18.E-02
cg11454719
PAX3
2
223155841
gene body
CGI
4.42.E-03
7.46.E-03
1.71.E-02
1.09.E-02
cg05530568
EBF1
5
158526614
promoter
CGI shore
4.66.E-03
2.08.E-02
2.08.E-02
1.34.E-02
cg05397934
-
X
57167668
intergenic
CGI shelf
4.66.E-03
3.17.E-02
1.94.E-02
1.47.E-02
cg10988027
-
3
45633138
intergenic
CGI shore
5.54.E-03
4.76.E-02
1.31.E-02
1.30.E-02
cg18810347
IKZF1
7
50344242
promoter
CGI
6.00.E-03
2.87.E-02
3.26.E-02
2.74.E-02
cg22946219
RAI1
17
17714414
3'UTR
CGI
6.10.E-03
4.86.E-02
1.19.E-03
1.76.E-02
cg14153722
MAPKAPK2
1
206858799
promoter
CGI
6.29.E-03
2.40.E-02
1.86.E-02
1.80.E-02
cg06776823
RIC8B
12
107170751
gene body
CGI shelf
6.81.E-03
3.76.E-02
2.59.E-02
1.40.E-02
cg26329756
IGF1R
15
99250482
gene body
CGI shore
6.88.E-03
3.74.E-02
9.90.E-03
1.76.E-02
cg05516100
-
17
1804784
intergenic
CGI shelf
7.42.E-03
6.12.E-02
4.42.E-02
3.78.E-02
cg09180894
ARHGEF16
1
3395053
gene body
CGI
8.01.E-03
4.63.E-02
1.15.E-02
1.70.E-02
cg05064223
PTPRN2
7
157611269
gene body
CGI shore
8.51.E-03
5.75.E-02
2.67.E-02
5.16.E-02
cg11926971
ZNF550
19
58068618
promoter
CGI shore
8.70.E-03
3.08.E-02
1.85.E-02
1.15.E-02
cg04517044
SMARCD3
7
150946998
promoter
CGI shore
9.05.E-03
6.34.E-02
2.08.E-02
5.12.E-02
cg27149388
AMIGO2
12
47473796
promoter
CGI
9.30.E-03
3.87.E-02
3.61.E-02
-1.17.E-02
cg16720675
ABHD3
18
19284817
promoter
CGI
9.32.E-03
8.71.E-06
4.61.E-02
-1.03.E-02
cg17982497
-
15
96906859
intergenic
CGI shore
9.69.E-03
9.42.E-03
4.27.E-02
1.19.E-02
5
140243301
gene body
CGI shore
1.00.E-02
8.60.E-02
4.44.E-02
3.04.E-02
PCDHA6;PCDHA
2;PCDHA1;PCDH
cg13298827
A9;PCDHA7;PCD
HA5;PCDHA3;PC
DHA4;PCDHA10;
PCDHA8
cg06820859
LATS2
13
21564784
gene body
CGI shore
1.04.E-02
4.64.E-02
3.33.E-02
1.31.E-02
cg09292876
-
20
39312434
intergenic
CGI
1.09.E-02
2.02.E-02
1.46.E-02
3.55.E-02
cg10349197
NEK4
3
52801074
gene body
CGI shelf
1.09.E-02
5.66.E-02
9.50.E-03
4.33.E-02
cg02144050
TBC1D25
X
48397520
promoter
CGI shore
1.11.E-02
7.26.E-02
2.13.E-03
2.15.E-02
cg05874882
-
4
1763078
intergenic
CGI shore
1.12.E-02
8.43.E-02
7.73.E-03
3.93.E-02
cg14006663
PITRM1
10
3215076
promoter
CGI
1.20.E-02
1.44.E-02
4.02.E-02
1.29.E-02
10
79686444
promoter
CGI
1.22.E-02
3.42.E-04
4.24.E-02
-1.54.E-02
cg24076633
LOC100128292;D
LG5
cg12461576
EPB41L4A
5
111755432
promoter
CGI
1.25.E-02
2.06.E-02
1.67.E-02
2.64.E-02
cg17485549
ADAM8
10
135083291
gene body
CGI shore
1.36.E-02
2.93.E-02
1.70.E-02
2.07.E-02
8
104427370
promoter
CGI
1.45.E-02
3.12.E-02
3.31.E-02
2.04.E-02
cg14694896
SLC25A32;DCAF
13
cg02895639
FAM19A5
22
48970993
promoter
CGI
1.47.E-02
2.62.E-02
2.73.E-02
1.35.E-02
cg05447486
RAP1A
1
112162367
promoter
CGI
1.47.E-02
1.74.E-04
1.27.E-02
-1.07.E-02
cg04803930
FBRSL1
12
133159472
gene body
CGI
1.63.E-02
4.24.E-02
2.59.E-02
1.16.E-02
cg06573718
IKBIP;APAF1
12
99038766
promoter
CGI
1.67.E-02
2.17.E-02
2.65.E-02
1.76.E-02
cg22276619
GFRA2
8
21645332
gene body
CGI
1.67.E-02
5.99.E-03
3.62.E-02
1.72.E-02
cg26301777
NAA16
13
41884544
promoter
CGI shore
1.78.E-02
6.73.E-02
2.05.E-02
1.18.E-02
cg07858745
GTF2I
7
74072514
promoter
CGI
1.86.E-02
6.87.E-02
4.16.E-02
-1.58.E-02
cg18289490
SPATA2
20
48532070
promoter
CGI
1.87.E-02
4.98.E-02
1.54.E-02
3.11.E-02
cg21520507
ARL1
12
101801499
promoter
CGI
1.88.E-02
2.39.E-02
1.97.E-02
1.35.E-02
cg08826460
LDLR
19
11201433
gene body
CGI
1.88.E-02
8.97.E-01
3.02.E-02
-3.22.E-02
cg09046939
CD8A
2
87017591
gene body
CGI
2.00.E-02
6.78.E-03
2.68.E-02
1.35.E-02
cg14783051
MCF2L
13
113663538
gene body
CGI
2.17.E-02
2.35.E-02
3.10.E-02
1.92.E-02
cg18203965
-
10
5570694
intergenic
CGI shelf
2.20.E-02
3.94.E-02
6.69.E-03
1.69.E-02
cg23151000
CYP1B1
2
38302892
promoter
CGI
2.20.E-02
9.86.E-03
2.64.E-02
1.82.E-02
cg11472297
-
22
35792396
intergenic
CGI shelf
2.27.E-02
3.33.E-02
1.37.E-02
1.24.E-02
cg22128035
MCFD2
2
47168977
promoter
CGI
2.29.E-02
2.02.E-02
2.48.E-02
1.80.E-02
cg22018784
FANCC
9
98079448
promoter
CGI
2.33.E-02
1.22.E-02
1.71.E-02
1.36.E-02
cg13784889
HERC3
4
89513377
promoter
CGI
2.41.E-02
2.60.E-02
3.87.E-02
3.12.E-02
cg02373393
ZZEF1;CYB5D2
17
4046391
promoter
CGI
2.45.E-02
1.16.E-02
3.90.E-02
1.03.E-02
1
762912
promoter
CGI
2.46.E-02
2.16.E-02
2.44.E-02
2.84.E-02
cg22394869
NCRNA00115;LO
C643837
cg13734410
PACSIN3
11
47207390
promoter
CGI
2.46.E-02
1.19.E-02
2.45.E-02
2.71.E-02
cg11079823
ACADM
1
76190140
promoter
CGI
2.51.E-02
1.39.E-02
2.37.E-05
1.24.E-02
cg20102246
PRKRIP1
7
102036757
promoter
CGI
2.54.E-02
8.57.E-03
1.86.E-02
2.24.E-02
cg04723170
-
2
96657499
intergenic
CGI
2.59.E-02
1.53.E-02
9.27.E-03
1.57.E-02
cg26681912
SLC19A2
1
169455321
promoter
CGI
2.60.E-02
2.70.E-02
4.33.E-02
1.59.E-02
cg01719141
EHMT1
9
140513215
promoter
CGI
2.62.E-02
2.45.E-02
2.80.E-02
2.28.E-02
cg11218415
-
8
104030731
intergenic
CGI shelf
2.64.E-02
9.16.E-02
3.89.E-02
2.13.E-02
cg07354515
-
12
11653827
intergenic
CGI shore
2.70.E-02
2.12.E-02
3.11.E-02
1.65.E-02
cg09604725
C16orf61
16
81040600
promoter
CGI
2.72.E-02
1.26.E-02
3.74.E-02
1.91.E-02
cg05865670
FLJ39582
22
21355860
promoter
CGI shore
2.72.E-02
1.99.E-02
3.45.E-02
1.92.E-02
cg10620501
PROSC
8
37620046
promoter
CGI
2.75.E-02
4.15.E-02
1.01.E-02
4.47.E-02
cg05247391
LACTB2
8
71581649
promoter
CGI
2.83.E-02
2.45.E-02
3.61.E-02
1.90.E-02
cg01726065
KIF7
15
90171768
gene body
CGI
2.84.E-02
3.29.E-02
1.02.E-02
1.40.E-02
cg05598205
ORC6L
16
46723426
promoter
CGI
2.85.E-02
2.27.E-02
4.13.E-02
1.61.E-02
cg23497529
-
14
100255608
intergenic
CGI shelf
2.85.E-02
8.27.E-02
3.91.E-02
1.46.E-02
cg07697635
SCAMP1
5
77656183
promoter
CGI
2.85.E-02
1.43.E-02
3.26.E-02
1.42.E-02
cg25082959
FGF14
13
103046930
gene body
CGI
2.90.E-02
1.51.E-02
3.28.E-03
1.31.E-02
cg24899068
RPS11
19
49999470
promoter
CGI
2.91.E-02
2.00.E-02
3.23.E-02
1.77.E-02
cg06277657
DGKI
7
137532374
promoter
CGI
2.95.E-02
2.87.E-03
5.10.E-03
2.30.E-02
cg19273746
B3GAT2
6
71666063
promoter
CGI
2.96.E-02
4.96.E-02
1.04.E-03
5.31.E-02
cg05332869
TOP1
20
39658073
gene body
CGI
2.98.E-02
1.28.E-02
4.38.E-02
1.28.E-02
cg21526238
PLAGL1
6
144329672
promoter
CGI
3.01.E-02
1.30.E-02
4.79.E-02
-2.48.E-02
cg23689517
PIGG
4
532975
gene body
CGI shelf
3.03.E-02
1.76.E-03
4.00.E-02
1.07.E-02
cg25884094
PCM1
8
17785204
promoter
CGI shelf
3.08.E-02
6.08.E-02
3.62.E-02
3.40.E-02
cg11786005
TBP
6
170863399
promoter
CGI
3.17.E-02
9.25.E-03
1.20.E-02
1.65.E-02
cg19978624
RASGEF1C
5
179557008
gene body
CGI shelf
3.26.E-02
3.01.E-02
4.90.E-02
1.25.E-02
cg04890770
ETNK1
12
22777991
promoter
CGI
3.39.E-02
1.69.E-02
2.81.E-02
2.18.E-02
cg25711779
EFEMP1
2
56149825
promoter
CGI shore
3.44.E-02
1.55.E-02
1.99.E-03
1.45.E-02
cg26650987
C5orf43
5
60458349
promoter
CGI
3.49.E-02
2.50.E-02
8.35.E-03
2.22.E-02
cg03309421
LSM5
7
32535387
promoter
CGI
3.51.E-02
1.10.E-02
2.82.E-02
2.04.E-02
cg19375044
TOMM40
19
45394343
promoter
CGI
3.51.E-02
1.14.E-02
1.19.E-02
1.02.E-02
cg05475543
FLJ13224
12
31477216
promoter
CGI
3.53.E-02
2.98.E-02
1.67.E-03
2.67.E-02
cg14209549
PITRM1
10
3215073
promoter
CGI
3.55.E-02
2.82.E-02
3.89.E-02
2.90.E-02
cg07732143
CPNE5
6
36807193
promoter
CGI
3.56.E-02
2.48.E-03
5.09.E-03
1.50.E-02
cg07751641
-
5
134826244
intergenic
CGI
3.56.E-02
1.53.E-02
3.59.E-02
2.22.E-02
cg09563731
MAP2K2
19
4090587
3'UTR
CGI
3.65.E-02
3.98.E-02
2.61.E-02
1.04.E-02
cg08881796
VPS53
17
618545
promoter
CGI
3.67.E-02
1.20.E-02
4.49.E-02
2.02.E-02
cg06502425
KIAA0141
5
141303480
promoter
CGI
3.72.E-02
1.78.E-02
1.24.E-02
1.65.E-02
cg03912740
C9orf96
9
136242381
promoter
CGI
3.73.E-02
9.40.E-03
4.34.E-03
1.01.E-02
cg15266508
COL9A3
20
61447742
promoter
CGI
3.74.E-02
1.48.E-02
3.77.E-03
1.00.E-02
cg12525736
ARF1
1
228269915
promoter
CGI
3.75.E-02
6.74.E-04
1.46.E-02
-1.15.E-02
cg02976543
PER2
2
239197607
promoter
CGI
3.82.E-02
3.71.E-02
3.23.E-02
4.41.E-02
cg25887236
MBP
18
74844781
promoter
CGI
3.85.E-02
1.46.E-02
2.90.E-02
-1.27.E-02
cg25718361
TBC1D22A
22
47424445
gene body
CGI
3.85.E-02
5.18.E-02
3.53.E-02
1.74.E-02
cg26337430
C1orf50
1
43232221
promoter
CGI
3.95.E-02
2.61.E-02
3.60.E-02
3.97.E-02
cg02055615
RREB1
6
7108063
promoter
CGI
4.00.E-02
3.74.E-06
6.52.E-03
3.19.E-02
cg10391629
AKAP11
13
42846072
promoter
CGI
4.06.E-02
1.57.E-02
2.45.E-02
2.06.E-02
cg14937492
MKI67IP
2
122494379
promoter
CGI
4.10.E-02
4.60.E-02
1.77.E-03
1.72.E-02
cg13057770
KATNAL1
13
30881766
promoter
CGI
4.12.E-02
2.46.E-02
1.32.E-02
1.00.E-02
cg06782697
TBX1
22
19743336
promoter
CGI
4.12.E-02
3.58.E-03
3.26.E-02
1.70.E-02
cg16257334
VARS2
6
30881842
promoter
CGI
4.13.E-02
2.09.E-02
2.33.E-02
1.37.E-02
cg12597389
NXPH1
7
8482235
gene body
CGI
4.13.E-02
1.75.E-03
6.30.E-05
2.74.E-02
cg10577006
SLIT2
4
20254140
promoter
CGI
4.18.E-02
1.08.E-02
1.61.E-03
1.45.E-02
16
81130092
promoter
CGI
4.19.E-02
1.03.E-02
5.16.E-03
1.22.E-02
cg07238189
LOC100329108;G
CSH
cg03381047
-
6
168078772
intergenic
CGI shore
4.23.E-02
2.58.E-02
1.08.E-02
1.81.E-02
cg21282183
MBD1
18
47808529
promoter
CGI
4.25.E-02
2.99.E-02
4.24.E-02
2.47.E-02
cg00752852
ARPC2
2
219082218
promoter
CGI shore
4.26.E-02
1.55.E-02
3.25.E-02
1.07.E-02
cg24838202
PSMC2
7
102988263
gene body
CGI shelf
4.32.E-02
1.32.E-02
3.94.E-02
1.38.E-02
cg17590003
-
17
25676574
intergenic
CGI
4.47.E-02
1.61.E-02
1.67.E-02
-1.09.E-02
cg25510115
ADAMTS17
15
100832329
gene body
CGI
4.50.E-02
1.99.E-02
1.76.E-02
1.10.E-02
cg14282180
MSH2
2
47630433
promoter
CGI
4.51.E-02
3.50.E-03
2.91.E-02
1.54.E-02
cg09788111
ACADSB
10
124768255
promoter
CGI
4.53.E-02
2.67.E-02
1.67.E-02
2.87.E-02
cg13803071
YWHAQ
2
9771081
promoter
CGI
4.60.E-02
1.05.E-02
3.36.E-02
3.62.E-02
cg15142485
HDAC4
2
240323713
promoter
CGI
4.61.E-02
2.55.E-02
3.26.E-02
3.58.E-02
cg07334977
LAMP3
3
182880768
promoter
CGI shore
4.73.E-02
1.28.E-02
4.82.E-02
1.67.E-02
cg01778190
LMF1
16
967680
gene body
CGI shore
4.79.E-02
2.65.E-02
5.51.E-03
1.04.E-02
cg21911861
SAMD4B
19
39832561
promoter
CGI
4.80.E-02
2.69.E-04
2.60.E-02
-1.41.E-02
cg05305025
RBBP8
18
20513713
promoter
CGI
4.82.E-02
7.86.E-03
8.73.E-03
1.23.E-02
cg21605986
KIAA1191
5
175788725
promoter
CGI
4.93.E-02
3.28.E-02
3.78.E-02
4.49.E-02
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