Meta-Analysis:CD:Jostins L:Nature: 2012:23128233

Overview

A GWA scan of 5,956 cases and 14,927 controls for Crohn's disease (CD) was carried out using HapMap phase 3 (CEU+TSI) data to impute 1.23M SNPs. Imputation was carried out using Beagle 3.1 and association was calculated using PLINK. A meta-analysis was perfomed by combining the above, filtered by P.association < 0.01, with a replication cohort of 14,763 Crohn's disease cases and 15,977 controls genotyped on the ImmunoChip platform. This identified 30 (16 novel) loci specific to Crohn's disease with a further 76 (24 novel) being indistinguishable from the related IBD disorder, ulcerative colitis. A further 64 loci reached genomewide significance in a combined analysis of Crohn's disease and ulcerative colitis (IBD), these are shown on the IBD study page

Study Paper

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. 2012-11-01

Study Type

Whole Genome Association Study

Samples

Group	Phenotype	Population	Cases	Controls	Families	Trios
Discovery	CRO		5937	8043	-	-
Replication	CRO		14763	15977	-	-

Exclusion Criteria

Discovery

In addition to previously reported cohort QC, samples were excluded due to...

Call rate <98%
Heterozygosity ±0.2

Markers were excluded due to...

HWE (controls) P<10^-6
HWE (cases) P<10^-10
Call rate <95%
Difference in call rate between cases and controls > 2%

Replication

Samples

Call rate <95%
Heterozygosity outside CI 95% per batch
Non-European ancestry
Abnormal mean-intensity values
Duplicate and closely-related samples

Markers

Call rate <98%
HWE P<10^-10
Manual QC for those SNPs with meta-analysis P<10^-5

Study Association

Region	Location	Gene(s)	Marker	Allele	MAF	P Value	Odds Ratio
1p12	chr1:119807450-120084479	ADAM30	rs3897478	T > C	0.110	1.97e-11^C	1.16 (1.1-1.22)^C
1p13.2	chr1:113288123-114002809	PTPN22 DCLRE1B	rs6679677	C > A	0.098	2.03e-15^C	1.19 (1.12-1.27)^C
1p31.1	chr1:70524556-70651887		rs2651244	G > A	0.397	2.14e-04^C	1.03 (0.99-1.06)^C
1p31.1	chr1:77522888-78355813		rs17391694	C > T	0.126	2.96e-09^C	1.14 (1.08-1.19)^C
1p31.3	chr1:67128876-67302310	IL12RB2 IL23R	rs11209026	G > A	0.067	1.02e-146^C	2.38 (2.17-2.56)^C
1p36.12	chr1:22326008-22411939		rs12568930	T > C	0.169	1.32e-03^C	1.06 (1.01-1.11)^C
1p36.23	chr1:7853370-8140630	TNFRSF9	rs35675666	G > T	0.169	1.13e-07^C	1.1 (1.05-1.15)^C
1p36.33	chr1:1190173-1452909	TNFRSF18 TNFRSF4	rs12103	G > A	0.181	6.96e-08^C	1.09 (1.04-1.13)^C
1q21.3	chr1:151565936-152018664	RORC	rs4845604	G > A	0.147	1.88e-06^C	1.11 (1.05-1.16)^C
1q22	chr1:155052885-156118465	MSTO1 UBQLN4 RIT1	rs670523	G > A	0.324	5.79e-11^C	1.09 (1.05-1.12)^C
1q23.3	chr1:160727284-160979324	F11R ITLN1 USF1 CD48 SLAMF7 CD244 SLAMF1 ARHGAP30	rs4656958	G > A	0.317	1.12e-05^C	1.05 (1.02-1.09)^C
1q23.3	chr1:161419627-161668253	FCRLA FCGR2A FCGR3A FCGR2B HSPA6 FCGR3B	rs1801274	A > G	0.475	1.53e-07^C	1.08 (1.04-1.11)^C
1q24.3	chr1:172711325-172972573	FASLG TNFSF18	rs9286879	A > G	0.236	5.53e-22^C	1.13 (1.08-1.17)^C
1q31.3	chr1:197342098-197969200	C1orf53	rs2488389	G > A	0.212	8.45e-13^C	1.12 (1.08-1.17)^C
1q32.1	chr1:200892467-201069559	KIF21B	rs7554511	C > A	0.280	7.81e-19^C	1.15 (1.11-1.19)^C
1q32.1	chr1:206709013-206867232	IL20 PIGR FCMR IL24 IL19 RASSF5 MAPKAPK2 IL10	rs3024505	G > A	0.159	2.48e-19^C	1.16 (1.11-1.21)^C
2p14	chr2:65250869-65490608	SPRED2	rs6740462	A > C	0.260	1.06e-08^C	1.11 (1.06-1.15)^C
2p15	chr2:62256286-62420888		rs10865331	G > A	0.374	9.77e-10^C	1.10 (1.06-1.13)^C
2p16.1	chr2:60706158-61642429	AHSA2 C2orf74 REL KIAA1841	rs7608910	A > G	0.392	6.92e-19^C	1.13 (1.09-1.17)^C
2p21	chr2:43221519-43708586		rs10495903	C > T	0.134	8.03e-12^C	1.11 (1.06-1.17)^C
2p23.2	chr2:28377859-28449611	BRE FOSL2	rs925255	C > T	0.456	2.67e-15^C	1.12 (1.09-1.16)^C
2p23.3	chr2:24464482-25234839	ADCY3	rs6545800	C > T	0.434	6.14e-16^C	1.14 (1.10-1.18)^C
2p23.3	chr2:27154127-28142797	UCN	rs1728918	G > A	0.409	4.86e-16^C	1.12 (1.09-1.16)^C
2q12.1	chr2:102238781-102651983	IL18R1 IL1RL1 IL18RAP IL1R1 IL1RL2 IL1R2	rs917997	C > T	0.235	3.12e-20^C	1.14 (1.10-1.18)^C
2q24.2	chr2:162104363-162502867	IFIH1	rs2111485	G > A	0.391	1.02e-03^C	1.05 (1.02-1.09)^C
2q32.3	chr2:190986040-191143008	STAT1 STAT4	rs1517352	C > A	0.392	1.93e-10^C	1.1 (1.05-1.14)^C
2q35	chr2:218074907-218395928	CXCR1 PNKD TMBIM1 CXCR2 SLC11A1 CTDSP1 ARPC2	rs2382817	C > A	0.399	1.28e-07^C	1.09 (1.05-1.12)^C
2q37.1	chr2:233232538-233674416	INPP5D ATG16L1	rs12994997	A > G	0.469	4.14e-70^C	1.23 (1.19-1.27)^C
2q37.1	chr2:230181042-230371171	SP140	rs6716753	T > C	0.191	1.17e-16^C	1.13 (1.09-1.18)^C
2q37.3	chr2:240619922-240712978	GPR35	rs3749171	C > T	0.177	3.02e-08^C	1.11 (1.06-1.15)^C
3p21.31	chr3:48465783-50711580	MST1R IP6K2 BSN UCN2 GPX1 PFKFB4 USP4 MST1 IP6K1	rs3197999	G > A	0.279	5.31e-29^C	1.16 (1.12-1.20)^C
3p24.3	chr3:18566300-18808423		rs4256159	C > T	0.145	9.00e-15^C	1.15 (1.10-1.21)^C
4p11	chr4:48158462-52069158	SLC10A4 TXK	rs6837335	G > A	0.352	1.75e-08^C	1.09 (1.05-1.12)^C
4q13.3	chr4:73859603-74142734	CXCL5 CXCL1 CXCL8 PF4V1 CXCL3 PF4 CXCL2 CXCL6	rs2472649	G > A	0.113	2.13e-02^C	1.08 (1.02-1.14)^C
4q24	chr4:101782996-102192580		rs13126505	G > A	0.067	2.33e-10^C	1.17 (1.10-1.25)^C
4q27	chr4:122017479-122644147	IL2 IL21	rs7657746	A > G	0.246	1.01e-09^C	1.11 (1.06-1.15)^C
5p13.1	chr5:40286865-40626651	PTGER4	rs11742570	C > T	0.390	1.81e-82^C	1.3 (1.25-1.33)^C
5p15.2	chr5:10667329-10833902	DAP	rs2930047	T > C	0.374	1.45e-07^C	1.08 (1.04-1.12)^C
5q11.2	chr5:56121772-56154384	IL31RA IL6ST	rs10065637	C > T	0.212	3.68e-12^C	1.12 (1.08-1.16)^C
5q13.2	chr5:73161293-73284584		rs7702331	A > G	0.325	5.63e-10^C	1.09 (1.05-1.12)^C
5q15	chr5:96743698-97141497	ERAP2 LNPEP ERAP1	rs1363907	G > A	0.428	5.62e-13^C	1.07 (1.04-1.11)^C
5q23.3	chr5:130189256-131985036		rs4836519	T > C	0.303	4.24e-10^C	1.09 (1.05-1.14)^C
5q31.1	chr5:132075186-132658977	ACSL6 IL5 IL13 SLC22A4 SLC22A5 IRF1 IL4 PDLIM4 IL3 CSF2	rs2188962	C > T	0.420	1.35e-52^C	1.22 (1.18-1.26)^C
5q31.3	chr5:142033064-142260854	NDFIP1 SPRY4	rs6863411	T > A	0.376	3.59e-14^C	1.1 (1.06-1.14)^C
5q33.1	chr5:150658703-151012930	TNIP1 IRGM	rs11741861	A > G	0.075	2.94e-37^C	1.32 (1.25-1.40)^C
5q33.3	chr5:159397971-159460964	IL12B	rs6871626	C > A	0.333	4.04e-36^C	1.20 (1.16-1.24)^C
5q35.2	chr5:173797287-174112331	CPEB4	rs17695092	T > G	0.293	4.68e-09^C	1.1 (1.05-1.14)^C
5q35.3	chr5:177079730-177421018	DOK3	rs12654812	G > A	0.343	1.90e-04^C	1.06 (1.03-1.10)^C
6p22.3	chr6:20639373-21029922		rs9358372	A > G	0.375	8.66e-14^C	1.11 (1.07-1.14)^C
6p22.3	chr6:21338901-21476386		rs12663356	C > T	0.468	4.01e-12^C	1.1 (1.06-1.14)^C
6p23	chr6:14691381-14736360		rs17119	A > G	0.194	8.51e-09^C	1.08 (1.04-1.12)^C
6q15	chr6:90097116-90319078		rs1847472	C > A	0.346	1.57e-10^C	1.09 (1.05-1.12)^C
6q21	chr6:111075054-111647042	FYN TRAF3IP2 REV3L	rs3851228	A > T	0.064	4.02e-07^C	1.14 (1.07-1.21)^C
6q21	chr6:105954686-106099497		rs6568421	A > G	0.288	8.24e-20^C	1.14 (1.10-1.18)^C
6q22.33	chr6:126764254-127221808		rs9491697	A > G	0.458	3.79e-10^C	1.08 (1.04-1.11)^C
6q22.33	chr6:127629641-128019645		rs13204742	G > T	0.127	8.38e-15^C	1.17 (1.12-1.23)^C
6q23.3	chr6:137568592-137806067	TNFAIP3	rs6920220	G > A	0.209	2.22e-03^C	1.06 (1.02-1.10)^C
6q24.2	chr6:143504346-143711180	PHACTR2	rs12199775	A > G	0.070	5.43e-07^C	1.15 (1.08-1.23)^C
6q25.3	chr6:158903940-159121739	TAGAP	rs212388	T > C	0.396	3.04e-14^C	1.11 (1.07-1.14)^C
6q27	chr6:166931410-167134466	RP11-517H2.6 CCR6 RNASET2 RPS6KA2	rs1819333	T > G	0.463	6.76e-21^C	1.11 (1.08-1.15)^C
7p12.2	chr7:50206640-50325467	IKZF1 ZPBP	rs1456896	T > C	0.316	7.28e-15^C	1.11 (1.06-1.15)^C
7p15.1	chr7:28080094-28222707	JAZF1 CREB5	rs864745	C > T	0.497	3.65e-09^C	1.09 (1.05-1.12)^C
7p15.2	chr7:26618343-27162670		rs10486483	G > A	0.239	2.56e-08^C	1.09 (1.05-1.13)^C
7q22.1	chr7:99119190-99271073	SMURF1	rs9297145	A > C	0.256	1.64e-08^C	1.09 (1.05-1.13)^C
7q22.1	chr7:100502511-100911543	EPO	rs1734907	G > A	0.161	1.67e-13^C	1.16 (1.11-1.21)^C
7q31.2	chr7:117234417-117597881		rs38904	T > C	0.471	3.76e-03^C	1.04 (1.0-1.08)^C
8q21.3	chr8:89628493-89942373	RIPK2	rs7015630	T > C	0.263	1.42e-08^C	1.08 (1.03-1.11)^C
8q24.13	chr8:125438839-125562774	TRIB1	rs921720	G > A	0.373	8.30e-20^C	1.11 (1.08-1.15)^C
8q24.21	chr8:129468135-129685804		rs1991866	C > G	0.432	8.95e-07^C	1.07 (1.03-1.10)^C
8q24.21	chr8:128484980-128585383		rs6651252	T > C	0.128	1.45e-16^C	1.19 (1.12-1.25)^C
9p24.1	chr9:4944089-5274545	JAK2	rs10758669	A > C	0.347	1.44e-31^C	1.18 (1.14-1.22)^C
9q22.31	chr9:91134438-91402091	NFIL3	rs4743820	T > C	0.296	4.90e-04^C	1.03 (1.0-1.08)^C
9q32	chr9:114715997-114937465	TNFSF8 TNC TNFSF15	rs4246905	C > T	0.289	6.23e-26^C	1.15 (1.1-1.19)^C
9q34.3	chr9:136243135-136514725	PMPCA CARD9 SDCCAG3 INPP5E	rs10781499	G > A	0.423	3.49e-48^C	1.21 (1.17-1.25)^C
10p11.21	chr10:34887225-35588558	CREM	rs11010067	C > G	0.352	2.49e-25^C	1.16 (1.12-1.20)^C
10p11.23	chr10:30398004-30522007	MAP3K8	rs1042058	C > T	0.398	5.93e-11^C	1.09 (1.05-1.12)^C
10p15.1	chr10:5987834-6098857	IL2RA IL15RA	rs12722515	C > A	0.160	3.76e-10^C	1.12 (1.08-1.18)^C
10q21.1	chr10:58064134-58408714	CISD1 IPMK	rs2790216	G > A	0.216	8.07e-09^C	1.08 (1.03-1.12)^C
10q21.2	chr10:62581266-62866159		rs10761659	G > A	0.459	6.37e-46^C	1.2 (1.16-1.25)^C
10q22.2	chr10:73639542-73945471		rs2227564	C > T	0.270	6.75e-10^C	1.1 (1.06-1.15)^C
10q22.3	chr10:79237086-79312766		rs1250546	A > G	0.423	3.15e-18^C	1.12 (1.09-1.16)^C
10q23.1	chr10:80326790-80603584	TSPAN14 FAM213A	rs6586030	G > A	0.204	9.24e-16^C	1.15 (1.1-1.19)^C
10q23.33	chr10:92439580-92742146		rs7911264	C > T	0.430	4.84e-05^C	1.06 (1.02-1.09)^C
10q24.2	chr10:99508770-99570210	NKX2-3	rs4409764	G > T	0.482	1.80e-41^C	1.18 (1.14-1.22)^C
11p15.5	chr11:1845142-1946041	LSP1 TNNI2	rs907611	G > A	0.318	6.77e-05^C	1.06 (1.02-1.10)^C
11q12.1	chr11:58132360-58690335	LPXN CNTF	rs10896794	T > C	0.249	1.21e-05^C	1.09 (1.04-1.12)^C
11q12.2	chr11:60962649-61068645	CD5 PTGDR2 CD6	rs11230563	C > T	0.347	1.89e-10^C	1.09 (1.05-1.14)^C
11q12.2	chr11:61749438-61917078	FADS1 MYRF FADS2	rs4246215	G > T	0.328	1.93e-15^C	1.11 (1.08-1.15)^C
11q13.1	chr11:64081858-64457156	TRPT1 FLRT1 RPS6KA4 CCDC88B	rs559928	C > T	0.188	4.22e-09^C	1.09 (1.04-1.14)^C
11q13.1	chr11:65604133-66296655	FOSL1 CTSW RELA SNX32	rs2231884	C > T	0.187	2.91e-10^C	1.12 (1.07-1.16)^C
11q13.5	chr11:76324636-76632292		rs2155219	T > G	0.498	9.56e-36^C	1.19 (1.15-1.23)^C
11q14.2	chr11:87236723-87522249		rs6592362	G > A	0.281	6.98e-05^C	1.07 (1.03-1.11)^C
11q23.3	chr11:118606652-118952438	CXCR5	rs630923	C > A	0.243	7.07e-09^C	1.09 (1.05-1.14)^C
12p13.2	chr12:12384138-12579426	BORCS5	rs11612508	A > G	0.273	3.33e-02^C	1.04 (1.00-1.07)^C
12q12	chr12:40223113-40613085	LRRK2	rs11564258	G > A	0.027	6.38e-29^C	1.46 (1.32-1.62)^C
12q13.11	chr12:47788458-47837647	VDR	rs11168249	T > C	0.461	9.57e-03^C	1.03 (1.00-1.07)^C
12q15	chr12:68036752-68116292	IL26 IFNG IL22	rs7134599	G > A	0.389	4.16e-05^C	1.05 (1.02-1.09)^C
13q12.13	chr13:26932960-26990142		rs17085007	T > C	0.185	3.79e-03^C	1.07 (1.02-1.11)^C
13q14.11	chr13:43662130-44029117	LACC1	rs3764147	A > G	0.231	2.19e-21^C	1.16 (1.11-1.20)^C
13q14.11	chr13:40435146-40471356		rs941823	C > T	0.249	8.45e-04^C	1.05 (1.01-1.09)^C
13q32.3	chr13:99110747-99432425	GPR18 GPR183	rs9557195	T > C	0.220	1.35e-12^C	1.12 (1.08-1.16)^C
14q24.1	chr14:68696738-68851345	ZFP36L1	rs194749	T > C	0.227	2.70e-10^C	1.09 (1.05-1.13)^C
14q24.3	chr14:75204956-75283172	MLH3 FOS	rs4899554	C > T	0.172	2.71e-08^C	1.1 (1.05-1.15)^C
14q31.3	chr14:87863352-88175959	GALC GPR65	rs8005161	C > T	0.086	1.96e-12^C	1.16 (1.09-1.22)^C
15q14	chr15:38522176-38679976	SPRED1 RASGRP1	rs16967103	T > C	0.194	3.88e-09^C	1.09 (1.05-1.13)^C
15q22.33	chr15:67120258-67176997	SMAD3	rs17293632	C > T	0.240	5.97e-16^C	1.10 (1.06-1.14)^C
15q26.1	chr15:90382489-90725453	CRTC3	rs7495132	C > T	0.103	6.61e-08^C	1.14 (1.08-1.2)^C
16p11.2	chr16:28283985-29014657	NUPR1 EIF3C RABEP2 SULT1A1 IL27 SULT1A2	rs26528	T > C	0.459	9.65e-22^C	1.13 (1.10-1.17)^C
16p12.2	chr16:23720685-23964030	PRKCB	rs7404095	C > T	0.424	1.61e-05^C	1.05 (1.02-1.09)^C
16p13.13	chr16:11210761-11380893	RMI2 LITAF SOCS1	rs529866	C > T	0.202	1.73e-16^C	1.18 (1.12-1.22)^C
16q12.1	chr16:50658453-50824433	NOD2 ADCY7	rs2066847	- > T	0.178	5.61e-166^C	1.56 (1.50-1.62)^C
16q24.1	chr16:85949450-85990498	IRF8	rs10521318	C > T	0.083	1.92e-08^C	1.2 (1.14-1.28)^C
17q11.2	chr17:27286355-27690219	NOS2 LGALS9C LGALS9	rs2945412	A > G	0.412	8.68e-17^C	1.14 (1.1-1.18)^C
17q12	chr17:34175049-34352741	CCL11 CCL13 CCL2	rs3091316	G > A	0.274	1.22e-26^C	1.16 (1.12-1.2)^C
17q12	chr17:39219977-40074859	GSDMB IKZF3 ORMDL3 ZPBP2 GSDMA	rs12946510	C > T	0.467	3.58e-25^C	1.15 (1.12-1.19)^C
17q21.2	chr17:42156716-42774617	STAT5A STAT3 STAT5B	rs12942547	A > G	0.422	3.34e-17^C	1.11 (1.08-1.15)^C
17q23.1	chr17:59412005-59997425	RPS6KB1 TUBD1	rs1292053	A > G	0.454	8.85e-13^C	1.10 (1.06-1.13)^C
18p11.21	chr18:12738414-12925254		rs1893217	A > G	0.160	3.05e-25^C	1.18 (1.13-1.24)^C
18q21.1	chr18:48827214-48922435	SMAD7	rs7240004	A > G	0.377	7.50e-04^C	1.03 (1.0-1.06)^C
18q22.2	chr18:69831437-69902924	CD226	rs727088	A > G	0.479	5.20e-05^C	1.06 (1.03-1.10)^C
19p13.2	chr19:10292692-10520699	PPAN-P2RY11 ICAM1 TYK2	rs11879191	G > A	0.203	1.78e-17^C	1.15 (1.1-1.19)^C
19p13.3	chr19:1090804-1183852	HMHA1 GPX4	rs2024092	G > A	0.215	8.26e-22^C	1.16 (1.11-1.20)^C
19q13.11	chr19:33219244-33272215	CEBPG	rs17694108	G > A	0.288	4.09e-09^C	1.09 (1.05-1.13)^C
19q13.32	chr19:46304332-46410492		rs4802307	G > T	0.292	2.00e-10^C	1.1 (1.06-1.14)^C
19q13.33	chr19:48592641-48763133	SPHK2 DBP IZUMO1 FUT2	rs516246	C > T	0.482	1.00e-15^C	1.11 (1.07-1.14)^C
19q13.42	chr19:54783517-54916142	NLRP7 KIR2DL1 NLRP2 LILRB4	rs11672983	G > A	0.336	4.00e-04^C	1.08 (1.04-1.12)^C
20q11.21	chr20:31995378-32517173	HCK	rs6142618	G > A	0.443	2.30e-09^C	1.09 (1.05-1.12)^C
20q11.21	chr20:32611779-33001967	DNMT3B	rs4911259	T > G	0.403	5.12e-06^C	1.08 (1.04-1.11)^C
20q13.12	chr20:45906223-46158839	CD40 MMP9 PLTP	rs1569723	A > C	0.248	9.95e-14^C	1.13 (1.09-1.18)^C
20q13.13	chr20:50301749-50423945	CEBPB	rs913678	T > C	0.325	4.78e-04^C	1.04 (1.01-1.09)^C
20q13.32	chr20:59153293-59295301	CTSZ ZNF831	rs259964	G > A	0.457	3.87e-11^C	1.10 (1.06-1.13)^C
20q13.33	chr20:63567747-63814828	TNFRSF6B LIME1 SLC2A4RG ZGPAT	rs6062504	G > A	0.298	2.45e-19^C	1.12 (1.09-1.16)^C
21q21.1	chr21:15326120-15470979		rs2823286	G > A	0.293	4.63e-28^C	1.18 (1.14-1.23)^C
21q22.2	chr21:39081110-39111851		rs2836878	G > A	0.272	2.80e-14^C	1.12 (1.08-1.16)^C
21q22.3	chr21:44152485-44266077	CH507-9B2.1 ICOSLG	rs7282490	A > G	0.406	2.55e-19^C	1.11 (1.07-1.14)^C
21q22.11	chr21:33370311-33842379	IFNAR1 IL10RB GART IFNAR2 IFNGR2 TMEM50B	rs2284553	G > A	0.399	2.14e-16^C	1.12 (1.09-1.16)^C
22q11.21	chr22:21454896-21649639	RIMBP3 YDJC CCDC116 MAPK1 UBE2L3	rs2266959	G > T	0.190	3.89e-16^C	1.13 (1.08-1.17)^C
22q12.2	chr22:29651931-30271212	LIF OSM MTMR3	rs2412970	A > G	0.452	5.94e-12^C	1.08 (1.05-1.12)^C
22q13.1	chr22:39253129-39364639	ATF4 APOBEC3G TAB1	rs2413583	C > T	0.167	4.35e-31^C	1.25 (1.19-1.3)^C
MHC	chr6:31253891-31375183	MICB NFKBIL1 HLA-C PSORS1C1	rs9264942	T > C	0.358	4.96e-28^C	1.15 (1.11-1.18)^C

Criteria

GDXHsS00021 meets the following criteria:

Criteria Name

Details

Disease Tags

Study for a Disease

CRO IBD

Publications

PMID	Title	First Author	Journal	Disease(s)	Date