Overview

Genome wide association study in 9772 multiple sclerosis cases from 15 countries, European ( 7597), USA (1382), Australia (647) and New Zealand (146), compared to 11479 European and 5370 USA controls. Cases and controls were of self-reported European ancestry. Case characteristic/diagnostic: Age at onset between 26.8 - 37.8 with a mean of 32.3, Expanded Disability Status Score (EDSS) mean 3.9, Multiple Sclerosis Severity Score (MSSS) mean 4.9.  Genotyping was performed on the Illumina platform and 465434 SNPs were available for analysis. Replication was done “in silico” using data from previously published GWAS, performed on a mixture of genotyping platforms. Replication analysis included data from 4218 cases and 7296 controls. Genotypes at untyped markers were imputed using data from HapMap phase II (release 22) and the software package MACH. 102 SNPs from the new Genome wide association study were tested in the replication data set and 29 novel loci were confirmed in addition to confirming the 23 of the 26 previously known loci.  GWAS p-value threshold (for 29 novel regions): Combined p-value < 5.0E-08.

Study Type
Whole Genome Association Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryMS977217376--
ReplicationMS42187296--
Exclusion Criteria
Sample Exclusion Criteria:
For summary of the total number of sample exclusions please refer to page 26 of the supplementary information.
 
SNP Exclustion Criteria:
  • Minor allele frequency  > 0.1% 
  • Call rate  > 98% (for external control data)
  • Plate association p-value > 1E-50 (for shared control data and internal MS data)
  • Hardy-Weinberg p-value > 1E-50 (for shared control data & internal MS data) and p-value > 1E-20 (for external control data)
  • Additional filters: Automated cluster checks and Beta-binomial modelling approaches were applied.
Please refer to page 30 of the supplementary information for more details about the SNP QC.

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.1chr1:116487687-116567720CD58  rs1335532A > G0.1313.20e-16C1.18 (1.12-1.23)D
1p21.2chr1:100744097-101199255EXTL2  rs12048904G > A0.3934.00e-08C1.10 (1.06-1.14)D
1p21.2chr1:100744097-101199255SLC30A7  RP11-421L21.2  rs11581062A > G0.2812.50e-10C1.13 (1.09-1.18)D
1p22.1chr1:92165805-93036894EVI5  rs11810217G > A0.2555.80e-15C1.15 (1.11-1.20)D
1p22.3chr1:85140978-85475461DDAH1  rs233100G > A0.4291.00e-06C1.09 (1.05-1.14)D
1p36.32chr1:2431888-2879054MMEL1  rs4648356C > A0.3191.00e-14C1.16 (1.12-1.2)D
1q23.1chr1:157510927-157848760FCRL3  rs3761959C > T0.4392.90e-06C1.1 (1.06-1.14)D
1q31.2chr1:192500477-192579099RGS1  rs1323292A > G0.1782.30e-08C1.12 (1.08-1.18)D
1q32.1chr1:200893429-201069559C1orf106  rs7522462G > A0.2691.90e-09C1.11 (1.06-1.15)D
2p13.3chr2:68309121-68631186PLEK  rs7595037T > C0.4435.10e-11C1.1 (1.06-1.14)D
2p21chr2:43085671-43159821rs12466022C > A0.2746.20e-10C1.1 (1.06-1.14)D
2q13chr2:111886554-112181465MERTK  rs17174870C > T0.2451.30e-08C1.1 (1.06-1.15)D
2q33.1chr2:199664087-200424675C2orf69  rs281783A > G0.1851.80e-04C1.11 (1.06-1.18)D
2q37.1chr2:230185270-230371171SP140  rs10201872G > A0.1611.80e-10C1.13 (1.08-1.19)D
3p14.3chr3:56813917-56922208ARHGEF3  rs1500710A > C0.3905.20e-05C1.09 (1.05-1.14)D
3p24.1chr3:27678872-27797643EOMES  rs11129295G > A0.3701.20e-09C1.11 (1.07-1.16)D
3p24.1chr3:27999281-28088981rs669607A > C0.4841.90e-15C1.13 (1.09-1.17)D
3p24.3chr3:16827477-17110801PLCL2  rs9821630A > G0.2843.90e-06C1.09 (1.05-1.14)D
3q12.3chr3:101953037-102091610NFKBIZ  rs771767G > A0.2718.60e-09C1.12 (1.08-1.16)D
3q13.33chr3:121896832-122127985CD86  rs4308217C > A0.3345.70e-08C1.1 (1.06-1.14)D
3q13.33chr3:119384793-119581808TIMMDC1  rs2293370G > A0.1832.70e-09C1.16 (1.11-1.22)D
3q13.33chr3:121619717-122104528SLC15A2  rs4285028A > C0.2741.80e-08C1.11 (1.08-1.16)D
3q13.33chr3:121896832-122127985CD86  rs9282641G > A0.0971.00e-11C1.2 (1.14-1.28)D
3q25.33chr3:159906172-160041614IL12A  rs2243123A > G0.2717.20e-06C1.09 (1.05-1.14)D
3q26.2chr3:169635396-169886565MYNN  rs10936599C > T0.2477.00e-07C1.1 (1.05-1.15)D
4q24chr4:102467408-103242450MANBA  rs228614G > A0.4821.40e-07C1.09 (1.05-1.14)D
4q35.1chr4:185635187-185663101SORBS2  rs6821894T > C0.3619.20e-05C1.08 (1.04-1.12)D
5p13.1chr5:39835735-40287627rs350058G > A0.0821.00e-04C1.14 (1.07-1.21)D
5p13.1chr5:40286865-40626651PTGER4  rs4613763A > G0.1272.50e-16C1.21 (1.15-1.28)D
5p13.2chr5:35795636-36035028IL7R  rs6897932C > T0.2691.70e-08C1.11 (1.06-1.16)D
5q31.1chr5:134069014-134441881TCF7  rs756699T > C0.1446.20e-07C1.12 (1.06-1.18)D
5q31.3chr5:141295751-141691834DIAPH1  rs2302103T > C0.4065.40e-04C1.08 (1.04-1.12)D
5q31.3chr5:142033064-142260854NDFIP1  rs1062158T > C0.3652.30e-06C1.09 (1.05-1.14)D
5q33.3chr5:159091760-159399302IL12B  rs2546890A > G0.4821.20e-11C1.1 (1.06-1.14)D
5q35.3chr5:177079730-177421018RGS14  rs4075958G > A0.2704.90e-07C1.11 (1.06-1.15)D
6p24.3chr6:7011620-7264441RREB1  rs11755724G > A0.3572.60e-06C1.08 (1.04-1.12)D
6q15chr6:90097116-90319078BACH2  rs12212193A > G0.4413.80e-08C1.09 (1.05-1.13)D
6q15chr6:89346362-89784679RRAGD  rs854917T > C0.2741.70e-04C1.09 (1.05-1.14)D
6q22.33chr6:127633469-128020756PTPRK  rs802734A > G0.3025.50e-09C1.1 (1.06-1.14)D
6q23.3chr6:134912824-135261929MYB  rs9321490A > G0.2261.60e-06C1.12 (1.07-1.17)D
6q23.3chr6:137006677-137196354IL22RA2  rs17066096A > G0.2436.00e-13C1.14 (1.09-1.18)D
6q23.3chr6:135268129-135820013AHI1  rs11154801C > A0.3571.00e-13C1.15 (1.10-1.19)D
6q23.3chr6:137552553-137804198rs13192841G > A0.2651.30e-08C1.10 (1.06-1.14)D
6q25.3chr6:158897742-159119181TAGAP  rs1738074T > C0.4176.80e-15C1.14 (1.09-1.18)D
7p14.1chr7:37324583-37400850ELMO1  rs11984075A > G0.1071.10e-05C1.13 (1.07-1.19)D
7p15.3chr7:22606135-22772302IL6  rs2066992G > T0.0516.30e-05C1.18 (1.1-1.28)D
7p21.3chr7:10480755-10856393NDUFA4  rs2214543C > T0.2781.60e-04C1.09 (1.05-1.14)D
7p22.2chr7:3053866-3151535CARD11  rs1843938G > A0.4181.10e-05C1.09 (1.05-1.13)D
7p22.3chr7:2301420-2446298CHST12  rs6952809G > A0.3153.60e-06C1.08 (1.04-1.12)D
7q36.1chr7:149421444-149668212ZNF767P  rs354033G > A0.2584.70e-09C1.1 (1.06-1.15)D
8p23.1chr8:9484196-9868683TNKS  rs6986386G > A0.2361.60e-05C1.09 (1.04-1.13)D
8q21.12chr8:78089756-78640408PKIA  rs1520333A > G0.2641.60e-07C1.11 (1.06-1.15)D
8q24.21chr8:127741008-127890277MYC  rs4410871C > T0.2787.70e-09C1.11 (1.08-1.16)D
8q24.21chr8:128105690-128266545PVT1  rs2019960A > G0.2055.20e-09C1.10 (1.05-1.15)D
9q22.2chr9:90680055-90855163SYK  rs290986A > G0.2009.10e-07C1.12 (1.08-1.18)D
10p11.22chr10:30843546-31191775ZNF438  rs793108C > T0.4982.60e-06C1.09 (1.05-1.14)D
10p15.1chr10:5988280-6131453IL2RA  rs3118470A > G0.3303.20e-11C1.12 (1.08-1.17)D
10p15.1chr10:5988280-6134149IL2RA  rs7090512A > G0.3014.60e-20C1.19 (1.13-1.24)D
10q22.3chr10:79258505-79313758ZMIZ1  rs1250550C > A0.3366.30e-09C1.10 (1.06-1.14)D
10q22.3chr10:76945935-77004770KCNMA1  rs7912269T > C0.0681.40e-05C1.16 (1.08-1.25)D
10q23.33chr10:92439580-92742146HHEX  rs7923837G > A0.3794.90e-09C1.1 (1.06-1.14)D
11q12.2chr11:60990871-61093417CD5  rs650258C > T0.3622.00e-11C1.12 (1.08-1.16)D
11q13.1chr11:64076473-64456055PRDX5  rs694739A > G0.3921.40e-04C1.08 (1.05-1.12)D
11q21chr11:95537638-95599614rs4409785A > G0.1756.30e-07C1.11 (1.06-1.16)D
11q23.3chr11:118606652-118952438CXCR5  rs630923C > A0.1622.80e-07C1.11 (1.06-1.18)D
11q23.3chr11:116311645-116384741rs491111G > A0.3534.80e-04C1.08 (1.05-1.12)D
11q24.1chr11:122607240-122721444UBASH3B  rs7941030A > G0.3811.60e-05C1.09 (1.05-1.13)D
12p13.31chr12:6312329-6354696TNFRSF1A  rs1800693A > G0.4074.10e-14C1.12 (1.08-1.16)D
12p13.31chr12:9364013-9819386CLECL1  rs10466829A > G0.4871.40e-08C1.09 (1.05-1.14)D
12q14.1chr12:57567711-58094884AGAP2  rs12368653G > A0.4831.70e-09C1.11 (1.06-1.15)D
13q14.2chr13:50160568-50490355DLEU1  rs806321T > C0.4655.00e-07C1.09 (1.05-1.14)D
13q14.11chr13:41543525-41723393rs17594362G > A0.1283.70e-06C1.12 (1.06-1.18)D
14q24.1chr14:68696033-68851345ZFP36L1  rs4902647C > T0.4679.30e-12C1.11 (1.08-1.15)D
14q24.3chr14:75476220-75565163BATF  rs2300603T > C0.2502.00e-08C1.11 (1.08-1.16)D
14q31.3chr14:87865031-88175959GPR65  rs2119704C > A0.0802.20e-10C1.27 (1.18-1.35)D
16p13.3chr16:996471-1059435SOX8  rs2744148A > G0.1678.40e-08C1.12 (1.07-1.17)D
16p13.13chr16:10923201-11218316CLEC16A  rs7200786G > A0.4638.50e-17C1.15 (1.11-1.20)D
16p13.13chr16:11286813-11406773RMI2  rs11864333A > G0.4823.60e-05C1.09 (1.05-1.14)D
16q23.2chr16:79595363-79627600MAF  rs386965A > G0.2283.90e-06C1.09 (1.05-1.14)D
16q24.1chr16:85949450-85990498IRF8  rs13333054G > A0.2161.30e-08C1.12 (1.08-1.17)D
17q21.2chr17:42156716-42774617STAT3  rs9891119A > C0.3511.80e-10C1.10 (1.06-1.14)D
17q21.31chr17:45212898-45573674MAP3K14  rs4792814C > T0.3953.00e-06C1.09 (1.05-1.14)D
17q21.32chr17:46789439-46973167WNT9B  rs1373089G > A0.4684.00e-05C1.08 (1.04-1.12)D
17q23.1chr17:59412005-59997425RPS6KB1  rs180515A > G0.3448.80e-08C1.11 (1.07-1.15)D
17q25.3chr17:80256957-80319669RNF213  rs8081176A > G0.3351.50e-05C1.09 (1.05-1.13)D
18q21.32chr18:58650125-58836789MALT1  rs7238078T > G0.2382.50e-09C1.11 (1.06-1.16)D
18q21.32chr18:58511402-58625662ALPK2  rs12456021G > A0.1913.60e-06C1.10 (1.05-1.15)D
19p13.2chr19:10272977-10517872ICAM3  rs2278442A > G0.3651.20e-04C1.08 (1.04-1.12)D
19p13.2chr19:10295959-10520699CDC37  rs8112449G > A0.3271.20e-06C1.1 (1.06-1.14)D
19p13.3chr19:6613822-6685293TNFSF14  rs1077667C > T0.2139.40e-14C1.16 (1.11-1.2)D
19p13.11chr19:18086825-18300992MPV17L2  rs874628A > G0.2781.30e-08C1.12 (1.08-1.18)D
19q13.31chr19:44577422-44692043PVR  rs7255066A > G0.2581.20e-06C1.10 (1.06-1.14)D
19q13.32chr19:47046533-47255671SAE1  rs307896G > A0.2934.60e-07C1.1 (1.06-1.14)D
19q13.33chr19:49217653-49427464DKKL1  rs2303759A > C0.2635.20e-09C1.11 (1.07-1.15)D
19q13.33chr19:48593054-48774825MAMSTR  rs281380A > G0.4021.90e-06C1.08 (1.04-1.12)D
20q13.2chr20:54114639-54169320CYP24A1  rs2762932A > G0.1588.10e-07C1.15 (1.09-1.21)D
20q13.2chr20:54160302-54206301CYP24A1  rs2248359C > T0.4032.50e-11C1.12 (1.08-1.16)D
20q13.12chr20:45903616-46155512NCOA5  rs2425752G > A0.2665.10e-10C1.10 (1.06-1.14)D
20q13.33chr20:63677259-63857674ZBTB46  rs6062314T > C0.0841.30e-07C1.18 (1.1-1.25)D
22q11.21chr22:21644220-22000056MAPK1  rs2283792G > T0.4874.70e-09C1.09 (1.05-1.14)D
22q12.3chr22:36855548-36932709NCF4  rs2072711G > A0.1666.30e-05C1.12 (1.07-1.17)D
22q13.33chr22:50491152-50633733ODF3B  rs140522G > A0.3261.70e-08C1.09 (1.05-1.14)D

Criteria

GDXHsS00007 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date