Post-GWAS analysis of schizophrenia

We developed a general computational framework for post-GWAS analysis to predict complex disease genes. We identified 132 schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are distal to the risk regions, likely under regulation of transcriptional regulatory elements therein contained.


Citation

Integrated post-GWAS analysis shed new light on the disease mechanisms of schizophrenia. Lin JR, Cai Y, Zhang Q, Zhang W, Nogales-Cadenas R, Zhang ZD (2016) Genetics 204(4):1587-1600.  pubmed   reprint 


Schizophrenia risk genes

SZ variant Chr Position * GWAS reference Predicted risk genes (& scores)
rs4648845 1 2387101 Ripke S et al
rs2252865 1 8422676 Ripke S et al
chr1_8424984_D 1 8424984 Ripke S et al
rs4846033 1 11788564 Sullivan PF et al
rs1009080 1 30431560 Ripke S et al
rs1498232 1 30433951 Ripke S et al
rs589249 1 37162352 Aberg KA et al GRIK3 (200.3)
rs11210892 1 44100084 Ripke S et al TIE1 (167.5)
rs12129573 1 73768366 Ripke S et al
rs10789369 1 73824909 Ripke S et al
rs12071951 1 97113915 Bergen SE et al
rs7544736 1 97164343 Purcell SM et al
rs76869799 1 97834525 Ripke S et al
rs1702294 1 98501984 Ripke S et al
rs1625579 1 98502934 Ripke S et al
rs1198588 1 98552832 Bergen SE et al
rs140505938 1 150031490 Ripke S et al MCL1 (182.2)
rs10489202 1 167903079 Shi Y et al
rs6670165 1 177280121 Ripke S et al
rs12140439 1 177722907 Aberg KA et al
rs10911902 1 186632317 Sullivan PF et al PTGS2 (1364.2), TPR (185.0), PDC (111.9)
rs7523273 1 207977083 Ripke S et al CD34 (346.3), CD46 (80.6)
rs7527939 1 210536025 Betcheva ET et al
rs1538774 1 243544827 Ripke S et al
rs77149735 1 243555105 Ripke S et al
rs10803138 1 243555219 Ripke S et al
rs6703335 1 243608967 Ripke S et al
rs14403 1 243663893 Ripke S et al
chr1_243881945_I 1 243881945 Ripke S et al
rs10429924 1 244390564 Levinson DF et al
rs10924245 1 245733608 Fanous AH et al
rs2373000 2 37592628 Ripke S et al
rs4381823 2 48047335 Aberg KA et al MSH6 (152.5)
rs11682175 2 57987593 Ripke S et al
rs75575209 2 58138192 Ripke S et al
rs2312147 2 58222928 Stefansson H et al
rs3768644 2 72361505 Ripke S et al
rs1170612 2 124983056 Levinson DF et al
rs12991836 2 145141541 Ripke S et al ZEB2 (140.3)
chr2_146436222_I 2 146436222 Ripke S et al
chr2_149429178_D 2 149429178 Ripke S et al
rs2909457 2 162845855 Ripke S et al DPP4 (933.8), GCA (88.6)
rs11693094 2 185601420 Ripke S et al
rs1344706 2 185778428 O'Donovan MC et al
rs4380187 2 185811940 Ripke S et al
rs59979824 2 193848340 Ripke S et al
rs17662626 2 193984621 Ripke S et al
rs6434928 2 198304577 Ripke S et al HSPD1 (154.5)
rs6704641 2 200164252 Ripke S et al
rs2949006 2 200715388 Ripke S et al
chr2_200825237_I 2 200825237 Ripke S et al
rs11685299 2 225391296 Ripke S et al
rs6704768 2 233592501 Ripke S et al
rs778371 2 233743109 Ripke S et al
rs13025591 2 236795343 Ripke S et al
rs17194490 3 2547786 Ripke S et al CNTN4 (184.2)
rs4330281 3 17859366 Ripke S et al
rs75968099 3 36858583 Ripke S et al
rs4624519 3 36862980 Ripke S et al
rs6550435 3 36864489 Ripke S et al
rs4687552 3 52838402 Ripke S et al PRKCD (439.5), ITIH4 (140.8), NISCH (138.6), GNL3 (89.9)
rs2535627 3 52845105 Ripke S et al PRKCD (439.5), ITIH4 (140.8), NISCH (138.6), GNL3 (89.9)
rs2239547 3 52855229 Ripke S et al PRKCD (439.5), ITIH4 (140.8), NISCH (138.6), GNL3 (89.9)
rs11130874 3 62064769 Ripke S et al
rs832187 3 63833050 Ripke S et al
rs17203055 3 119084331 Aberg KA et al
rs7432375 3 136288405 Ripke S et al
rs1351267 3 151763701 Fanous AH et al
rs6782299 3 180550702 Purcell SM et al
rs1879248 3 180551214 Ripke S et al
chr3_180594593_I 3 180594593 Ripke S et al
rs9841616 3 181167585 Ripke S et al SOX2 (198.1)
rs959770 4 2395297 Fanous AH et al ADD1 (129.7)
rs215411 4 23423603 Ripke S et al PPARGC1A (250.8)
rs35518360 4 103146890 Ripke S et al
rs11098403 4 118646907 Lencz T et al
rs10520163 4 170626552 Ripke S et al CLCN3 (131.4)
rs1106568 4 176861301 Ripke S et al
rs2726807 4 183137398 Levinson DF et al TENM3 (98.4)
rs1501357 5 45364875 Ripke S et al HCN1 (146.9)
rs10052004 5 56666500 Fanous AH et al
rs171748 5 60499131 Ripke S et al
rs4391122 5 60598543 Ripke S et al
rs7709645 5 60731458 Bergen SE et al
rs17206232 5 64433400 Fanous AH et al
rs16867576 5 88746331 Ripke S et al MEF2C (170.5)
rs6878284 5 101769726 Ripke S et al PAM (188.1)
rs1502844 5 101859317 Stefansson H et al PAM (188.1)
rs4388249 5 109036066 Ripke S et al PJA2 (145.9)
rs10043984 5 137712121 Ripke S et al EGR1 (1060.1), CTNNA1 (106.0)
rs3849046 5 137851192 Ripke S et al EGR1 (1060.1), CTNNA1 (106.0)
chr5_140143664_I 5 140143664 Ripke S et al CD14 (1051.8), HBEGF (189.8), IK (134.5)
rs79212538 5 151993104 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs111294930 5 152177121 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs2910032 5 152540354 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs2973155 5 152608619 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs17504622 5 152654479 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs12522290 5 152797656 Ripke S et al GRIA1 (344.5), NMUR2 (167.7)
rs11740474 5 153680747 Ripke S et al
rs12210050 6 475489 Levinson DF et al
rs13194053 6 27143883 Shi J et al
rs6932590 6 27248931 Stefansson H et al
rs16897515 6 27278020 Aberg KA et al
rs17693963 6 27710165 Bergen SE et al
rs1635 6 28227604 Yue WH et al
rs115329265 6 28712247 Ripke S et al
rs2523722 6 30165273 Donnelly P et al
rs2021722 6 30174131 Ripke S et al
rs1046089 6 31602967 Aberg KA et al CYP21A2 (299.8), AIF1 (185.2), APOM (147.1), AGER (105.8), CLIC1 (80.6)
rs3132935 6 32171075 Aberg KA et al CYP21A2 (299.8), TAP1 (173.0), NOTCH4 (151.4), TNXB (137.0), HLA-DQB1 (114.6), HLA-DRB1 (107.4), AGER (105.8), HLA-DRA (86.5)
rs3131296 6 32172993 Stefansson H et al CYP21A2 (299.8), TAP1 (173.0), NOTCH4 (151.4), TNXB (137.0), HLA-DQB1 (114.6), HLA-DRB1 (107.4), AGER (105.8), HLA-DRA (86.5)
rs114002140 6 32431962 Ripke S et al CYP21A2 (299.8), TAP1 (173.0), NOTCH4 (151.4), TNXB (137.0), HLA-DQB1 (114.6), HLA-DRB1 (107.4), AGER (105.8), HLA-DRA (86.5)
rs4530903 6 32581889 Fanous AH et al CYP21A2 (299.8), TAP1 (173.0), NOTCH4 (151.4), TNXB (137.0), HLA-DQB1 (114.6), HLA-DRB1 (107.4), AGER (105.8), HLA-DRA (86.5)
rs9272219 6 32602269 Shi J et al CYP21A2 (299.8), TAP1 (173.0), NOTCH4 (151.4), TNXB (137.0), HLA-DQB1 (114.6), HLA-DRB1 (107.4), AGER (105.8), HLA-DRA (86.5)
rs16869652 6 33851173 Levinson DF et al
rs1339227 6 73155701 Ripke S et al RIMS1 (357.2)
chr6_84280274_D 6 84280274 Ripke S et al
rs117074560 6 96459651 Ripke S et al
rs12666575 7 2004421 Bergen SE et al
rs6461049 7 2017445 Ripke S et al
chr7_2025096_I 7 2025096 Ripke S et al
chr7_24747494_D 7 24747494 Ripke S et al
rs12699131 7 71751316 Ripke S et al
rs12704290 7 86427626 Ripke S et al GRM3 (378.2)
rs7341475 7 103404815 Shifman S et al RELN (562.0)
rs6466055 7 104929064 Ripke S et al
rs211829 7 110048893 Ripke S et al IMMP2L (153.6)
rs13240464 7 110898915 Ripke S et al IMMP2L (153.6), DOCK4 (90.2)
rs7801375 7 131567263 Ripke S et al
rs3735025 7 137074844 Ripke S et al PTN (174.6)
rs10503253 8 4180844 Ripke S et al
rs10503256 8 4214179 Bergen SE et al
rs7017212 8 10022938 Ma X et al
rs73229090 8 27442127 Ripke S et al CLU (348.9), EPHX2 (192.7)
rs16887244 8 38031345 Shi Y et al FGFR1 (926.8), STAR (822.7)
rs6984242 8 60700469 Ripke S et al
rs7819570 8 89588626 Ripke S et al MMP16 (303.7)
rs11995572 8 89592083 Ripke S et al MMP16 (303.7)
rs7004633 8 89760311 Ripke S et al MMP16 (303.7)
rs36068923 8 111485761 Ripke S et al KCNV1 (88.8)
rs4129585 8 143312933 Ripke S et al
rs7045881 9 26935996 Athanasiu L et al
rs489332 9 78028346 Fanous AH et al
rs11139497 9 84739941 Ripke S et al
rs1572299 9 121346417 Stefansson H et al
rs17691888 10 18734528 Ripke S et al CACNB2 (101.7)
rs7893279 10 18745105 Ripke S et al CACNB2 (101.7)
rs3847375 10 21567565 Levinson DF et al
rs1412115 10 34088053 Alkelai A et al PARD3 (100.2)
rs10900020 10 44827197 Fanous AH et al CXCL12 (1114.3)
rs10761482 10 62085337 Athanasiu L et al ANK3 (135.1)
rs16915157 10 62346638 Ripke S et al ANK3 (135.1)
rs7907645 10 104423800 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs11191419 10 104612335 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs7085104 10 104628873 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs7897654 10 104662458 Aberg KA et al CYP17A1 (416.5), NEURL (127.1)
rs55833108 10 104741583 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs7914558 10 104775908 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs11191580 10 104906211 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
chr10_104957618_I 10 104957618 Ripke S et al CYP17A1 (416.5), NEURL (127.1)
rs4757144 11 13331226 Borglum AD et al ARNTL (359.6)
rs4356203 11 17160148 Ripke S et al PIK3C2A (213.8), NUCB2 (111.3)
rs11027857 11 24403620 Ripke S et al
rs1602565 11 29162136 O'Donovan MC et al
rs11038167 11 44843134 Yue WH et al
chr11_46350213_D 11 46350213 Ripke S et al MDK (197.0), CHRM4 (160.6), DGKZ (148.9)
rs9420 11 57510294 Ripke S et al SERPING1 (137.5), CTNND1 (105.5)
rs12421382 11 109378071 Ripke S et al
rs2514218 11 113392994 Ripke S et al DRD2 (1420.9), HTR3B (125.1)
rs77502336 11 123394636 Ripke S et al
rs12807809 11 124606285 Stefansson H et al NRGN (90.1)
rs55661361 11 124613957 Ripke S et al NRGN (90.1)
rs7930295 11 125313599 Aberg KA et al EI24 (220.3), CHEK1 (136.9)
rs11220082 11 125323965 Bergen SE et al EI24 (220.3), CHEK1 (136.9)
rs548181 11 125461709 Ripke S et al EI24 (220.3), CHEK1 (136.9)
rs10791097 11 130718630 Ripke S et al
rs7940866 11 130817579 Ripke S et al
rs10894294 11 130830748 Ripke S et al
rs75059851 11 133822569 Ripke S et al
rs2007044 12 2344960 Ripke S et al CACNA1C (597.1)
rs1006737 12 2345295 Ripke S et al CACNA1C (597.1)
rs4765905 12 2349584 Ripke S et al CACNA1C (597.1)
rs2239063 12 2511831 Ripke S et al CACNA1C (597.1)
rs16934812 12 29872318 Levinson DF et al
rs679087 12 29917265 Ripke S et al
rs324017 12 57487814 Ripke S et al LRP1 (692.5), STAT6 (144.1), MYO1A (138.6), TAC3 (113.4)
rs12826178 12 57622371 Ripke S et al LRP1 (692.5), STAT6 (144.1), MYO1A (138.6), TAC3 (113.4)
rs12426725 12 81843128 Levinson DF et al
rs4240748 12 92246786 Ripke S et al BTG1 (100.8)
rs10860964 12 103596455 Ripke S et al
rs4766428 12 110723245 Ripke S et al ATP2A2 (215.8)
rs1920592 12 114705586 Fanous AH et al
rs11064768 12 119818509 Kirov G et al
rs2851447 12 123665113 Ripke S et al
rs11532322 12 123731423 Ripke S et al
rs9512730 13 28077144 Sullivan PF et al
rs2323266 13 61965303 Fanous AH et al
rs2068012 14 30190316 Ripke S et al PRKD1 (1104.4)
rs2332700 14 72417326 Ripke S et al RGS6 (99.8)
rs2693698 14 99719219 Ripke S et al
rs12887734 14 104046834 Ripke S et al
rs56205728 15 40567237 Ripke S et al RAD51 (481.9), PLCB2 (209.8), PAK6 (149.7)
rs1869901 15 40595627 Ripke S et al RAD51 (481.9), PLCB2 (209.8), PAK6 (149.7)
rs7172342 15 61336442 Fanous AH et al
rs4775413 15 61840103 Ripke S et al
rs12903146 15 61854663 Ripke S et al
rs12592967 15 61870943 Bergen SE et al
rs12148337 15 70589272 Ripke S et al
rs190065944 15 78859610 Ripke S et al CHRNA3 (323.5), CHRNB4 (269.3), CHRNA5 (161.0)
rs8042374 15 78908032 Ripke S et al CHRNA3 (323.5), CHRNB4 (269.3), CHRNA5 (161.0)
rs950169 15 84706461 Ripke S et al
rs16977195 15 86984240 Sullivan PF et al
rs4702 15 91426560 Ripke S et al FURIN (326.3), FES (286.1), SV2B (107.8)
rs9922678 16 9946319 Ripke S et al GRIN2A (1385.0)
rs12922317 16 12077632 Borglum AD et al
rs7192086 16 13061611 O'Donovan MC et al
rs7405404 16 13749859 Ripke S et al ERCC4 (147.7)
rs151222 16 20674492 Sullivan PF et al
rs433598 16 20680206 Athanasiu L et al
rs12691307 16 29939877 Ripke S et al MAPK3 (915.7), DOC2A (249.6), TAOK2 (93.7)
rs17290922 16 57024317 Fanous AH et al CCL22 (159.4), CETP (99.7)
rs12325245 16 58681393 Ripke S et al
rs8044995 16 68189340 Ripke S et al PLA2G15 (854.0), LCAT (148.3), SLC12A4 (100.3)
rs8057927 16 82692812 Borglum AD et al CDH13 (231.7)
rs4523957 17 2208899 Ripke S et al SRR (104.4)
rs8082590 17 17958402 Ripke S et al SREBF1 (388.5), FLII (87.9), MYO15A (84.0)
rs1455244 18 11494199 Fanous AH et al GNAL (612.4)
rs2048485 18 42090667 Levinson DF et al
chr18_52749216_D 18 52749216 Ripke S et al TCF4 (522.1)
rs12966547 18 52752017 Ripke S et al TCF4 (522.1)
rs4801131 18 52752700 Ripke S et al TCF4 (522.1)
rs1261117 18 52949657 Aberg KA et al TCF4 (522.1)
rs17594526 18 53058238 Purcell SM et al TCF4 (522.1)
rs78322266 18 53063676 Ripke S et al TCF4 (522.1)
rs9960767 18 53155002 Stefansson H et al TCF4 (522.1)
rs17512836 18 53194961 Ripke S et al TCF4 (522.1)
rs9636107 18 53200117 Ripke S et al TCF4 (522.1)
rs72934570 18 53533189 Ripke S et al TCF4 (522.1)
rs715170 18 53795514 Ripke S et al TCF4 (522.1)
rs4798896 18 75912922 Fanous AH et al
rs7233060 18 77392379 Fanous AH et al
rs2905424 19 19473445 Ripke S et al
rs2905426 19 19478022 Ripke S et al
rs2053079 19 30987423 Ripke S et al
rs12611334 19 40229409 Aberg KA et al
rs4803480 19 42066279 Alkelai A et al
rs56873913 19 50091199 Ripke S et al RRAS (127.3), PRMT1 (116.7)
rs6065094 20 37453194 Ripke S et al
rs7267348 20 48131036 Ripke S et al PTGIS (155.5)
rs11699237 20 55683996 Fanous AH et al BMP7 (210.8)
rs9611198 22 39955873 Donnelly P et al et al
chr22_39987017_D 22 39987017 Ripke S et al
rs9607782 22 41587556 Ripke S et al EP300 (210.8), RANGAP1 (91.0)
rs1023500 22 42340844 Ripke S et al CYP2D6 (275.3), SREBF2 (105.2)
rs6002655 22 42603814 Ripke S et al CYP2D6 (275.3), SREBF2 (105.2)
rs138880 22 50218611 Aberg KA et al MAPK11 (97.4), MLC1 (80.7)
rs12845396 X 6029533 Ripke S et al NLGN4X (554.6)
rs1378559 X 21380266 Ripke S et al CNKSR2 (83.6)
rs5937157 X 68377126 Ripke S et al
rs2159767 X 147381021 Sullivan PF et al FMR1 (85.7)
rs2269372 X 153207545 Wong EH et al OPN1LW (359.6), MECP2 (310.3), IRAK1 (301.1), FLNA (246.1), AVPR2 (229.9), HCFC1 (122.0), L1CAM (103.6), ARHGAP4 (89.0)


 * All positions are based on the GRCh37/hg19 human genome assembly.