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