Overview

In discovery phase genotyping was carried out using immunochip platform on 14,498 Multiple sclerosis cases and 24,091 controls of european ancestry. Data was QC'ed and then analysed using PLINK by 11-country strata, based on ascertation. A replication phase was carried out using 14,802 cases and 26,703,  controls genotyped in previous GWAS studies, leveraging imputation of phase 1a 1000 genomes data (BEAGLE).  In total after combining discovery and replication phases in a meta-anlysis, 48 novel susceptibility variants were discovered in 45 discrete loci.

Study Type
Case-Control Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryMS1449824091--
ReplicationMS1480226703--
Exclusion Criteria

Samples

  • Reported gender and genotyping gender mismatch
  • Call rate < 95 %
  • Heterozygosity > 3 SD from mean
  • Excessive identity by descent.
  • Population outliers identified through PCA analysis
  • Mendelian error within family

SNPs

  • Call rate < 98%
  • HWE deviation p <= 1 x 10-5
  • Differential missingness between cases and controls
  • Monomophic SNPs

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p12chr1:119621680-119802828PHGDH  rs666930G > A0.4706.00e-12C1.09D
1p13.1chr1:116487687-116567720CD58  rs6677309A > C0.1205.40e-42C1.33D
1p21.2chr1:100744097-101194566VCAM1  rs7552544A > G0.4401.90e-16C1.08D
1p22.1chr1:92163769-93010941EVI5  rs41286801G > A0.1401.40e-26C1.20D
1p22.3chr1:85138055-85475461BCL10  rs12087340G > A0.0901.10e-20C1.22D
1p22.3chr1:85215222-85475616DDAH1  rs11587876A > G0.2104.40e-09C1.12D
1p36.31chr1:6276497-6504096PLEKHG5  rs3007421G > A0.1204.70e-10C1.12D
1p36.32chr1:2431888-2879054MMEL1  rs3748817A > G0.3601.30e-26C1.14D
1q23.1chr1:157516546-157895873FCRL1  rs2050568G > A0.4701.50e-10C1.08D
1q23.3chr1:160710974-160952405SLAMF7  rs35967351A > T0.3304.40e-11C1.09D
1q31.2chr1:192500477-192579099RGS1  rs1359062C > G0.1804.80e-20C1.18D
1q32.1chr1:200892467-201069559C1orf106  rs55838263A > G0.2904.00e-19C1.12D
2p14chr2:68308313-68455124PLEK  rs7595717G > A0.2601.20e-13C1.10D
2p16.1chr2:60694033-61609638LINC01185  rs842639A > G0.3502.00e-14C1.11D
2p21chr2:43092906-43187750rs2163226A > G0.2902.10e-16C1.1D
2p23.3chr2:24464482-25078886CENPO  rs4665719A > G0.2503.10e-09C1.09D
2q32.3chr2:191050989-191166501STAT4  rs9967792G > A0.3803.50e-12C1.11D
2q37.1chr2:230211574-230371171SP140  rs9989735G > C0.1804.20e-23C1.17D
3p13chr3:71383457-71585992FOXP1  rs9828629G > A0.3801.90e-10C1.08D
3p22.3chr3:32856713-32998085CCR4  rs4679081G > A0.4802.20e-09C1.08D
3p24.1chr3:27999281-28088981rs1813375C > A0.4701.90e-32C1.15D
3p24.1chr3:27639513-27794554EOMES  rs2371108C > A0.3801.50e-15C1.08D
3p24.3chr3:18566300-18815368rs11719975G > C0.2701.10e-08C1.09D
3q13.33chr3:119384793-119581808TIMMDC1  rs1131265C > G0.2001.40e-23C1.19D
3q13.33chr3:121849748-122126077CD86  rs2255214C > A0.4801.20e-24C1.14D
3q13.33chr3:121616614-122032684IQCB1  rs1920296C > A0.3606.50e-22C1.14D
3q25.33chr3:159872508-160007733IL12A  rs1014486A > G0.4301.10e-18C1.11D
4q24chr4:105002488-105561558TET2  rs2726518C > A0.4503.90e-08C1.09D
4q24chr4:102467408-103205026MANBA  rs7665090G > A0.4801.00e-08C1.08D
5p13.1chr5:40286865-40626651rs6880778G > A0.4008.10e-20C1.1D
5p13.2chr5:35797278-36035028IL7R  rs6881706C > A0.2804.30e-17C1.12D
5q11.2chr5:56122309-56161300ANKRD55  rs71624119G > A0.2403.40e-13C1.12D
5q31.1chr5:134069014-134441881TCF7  rs756699A > G0.1308.80e-11C1.12D
5q31.3chr5:142033064-142260854NDFIP1  rs371522651C > A0.3903.60e-09C1.08D
5q35.3chr5:177079730-177421018RGS14  rs4976646A > G0.3404.40e-18C1.13D
6p21.31chr6:36376436-36646035PXT1  rs941816A > G0.1803.90e-12C1.13D
6p23chr6:14691381-14736360rs17119A > G0.1901.00e-10C1.11D
6q15chr6:90097116-90319078BACH2  rs72928038G > A0.1701.50e-15C1.11D
6q23.3chr6:137006677-137196354IL22RA2  rs17066096A > G0.2301.60e-23C1.14D
6q23.3chr6:137552553-137804198rs7769192G > A0.4503.30e-09C1.08D
6q23.3chr6:135268129-135820013AHI1  rs11154801C > A0.3701.80e-20C1.11D
6q23.3chr6:137749522-137981174TNFAIP3  rs67297943A > G0.2205.50e-13C1.12D
6q25.3chr6:158901294-159120449TAGAP  rs212405T > A0.3808.00e-21C1.15D
7p12.2chr7:50212219-50325817IKZF1  rs201847125G > A0.3001.20e-11C1.11D
7p14.1chr7:37318708-37399609ELMO1  rs60600003A > C0.1006.00e-14C1.16D
7p15.1chr7:28080094-28222707JAZF1  rs917116A > C0.2003.30e-09C1.12D
7p15.2chr7:26619513-27166372rs706015A > C0.1801.10e-09C1.14D
7p22.2chr7:3053866-3151535CARD11  rs1843938G > A0.4401.20e-10C1.08D
8q21.12chr8:78501108-78839890ZC2HC1A  rs1021156G > A0.2408.50e-17C1.12D
8q24.21chr8:128105690-128266327MIR1208  rs759648A > C0.3105.00e-10C1.09D
8q24.21chr8:127078717-127221075rs2456449A > G0.3601.80e-09C1.10D
8q24.21chr8:127741008-127890277PVT1  MIR1204  rs4410871G > A0.2804.30e-16C1.12D
10p11.22chr10:30843546-31191775rs793108A > G0.5006.10e-12C1.09D
10p15.1chr10:5988280-6129961IL2RA  rs2104286A > G0.2802.30e-47C1.2D
10q22.2chr10:73639542-73945471C10orf55  rs2688608A > C0.4504.60e-08C1.08D
10q22.3chr10:79252314-79312766ZMIZ1  rs1782645G > A0.4302.50e-15C1.09D
10q23.33chr10:92439580-92742146HHEX  rs7923837G > A0.3904.30e-17C1.11D
11p11.2chr11:46326774-49110443AGBL2  rs7120737A > G0.1501.00e-09C1.13D
11q12.2chr11:60971360-61068645CD6  rs34383631G > A0.4003.70e-23C1.11D
11q13.1chr11:64076473-64456055PRDX5  rs694739A > G0.3802.00e-09C1.08D
11q23.3chr11:118441401-118893027TREH  rs533646G > C0.3207.60e-11C1.1D
11q23.3chr11:118523399-118918317CXCR5  rs9736016T > A0.3703.00e-15C1.1D
11q23.3chr11:118610716-118958811CXCR5  rs523604A > G0.4706.20e-15C1.09D
12p13.31chr12:6312329-6354696TNFRSF1A  rs1800693A > G0.4006.70e-28C1.14D
12p13.31chr12:9410118-9820167CD69  rs11052877A > G0.3605.60e-13C1.10D
12p13.31chr12:6373620-6414083LTBR  rs12296430G > C0.1907.20e-14C1.14D
12q14.1chr12:57576969-58094884TSFM  rs201202118A > T0.3309.00e-22C1.14D
12q24.31chr12:122875604-123523526PITPNM2  rs7132277G > A0.1901.90e-13C1.10D
13q32.3chr13:99392419-99584483MIR548AN  rs4772201A > G0.1801.30e-10C1.12D
14q24.1chr14:68696738-68851345ZFP36L1  rs2236262A > G0.5002.50e-12C1.08D
14q31.3chr14:87857711-88175959GALC  rs74796499C > A0.0502.40e-20C1.32D
14q32.32chr14:102585564-102957748TRAF3  rs12148050G > A0.3505.10e-13C1.08D
15q25.1chr15:78696056-78968794CTSH  rs59772922A > G0.1701.20e-08C1.11D
15q26.1chr15:90268570-90667491IQGAP1  rs8042861C > A0.4402.20e-09C1.08D
16p11.2chr16:29834364-30494500MAPK3  rs7204270G > A0.5001.60e-11C1.09D
16p13.13chr16:10945836-11268038CLEC16A  rs4780346G > A0.2304.40e-10C1.09D
16p13.13chr16:11227066-11392189RMI2  rs6498184G > A0.1907.40e-18C1.15D
16p13.13chr16:10923201-11220282CLEC16A  rs12927355G > A0.3206.40e-46C1.2D
16q22.1chr16:68402003-68815934CDH3  rs1886700G > A0.1401.30e-08C1.11D
16q23.1chr16:79072922-79097496WWOX  rs12149527G > A0.4703.30e-11C1.08D
16q23.2chr16:79595363-79627600MAF  rs7196953G > A0.2901.00e-10C1.08D
16q24.1chr16:85948640-85990498IRF8  rs35929052G > A0.1105.90e-12C1.14D
17q12chr17:39219977-40074859IKZF3  rs12946510G > A0.4702.90e-09C1.08D
17q21.2chr17:42156716-42774617STAT3  rs4796791G > A0.3603.70e-20C1.10D
17q21.32chr17:47231738-47798656NPEPPS  rs4794058A > G0.5001.00e-13C1.08D
17q23.1chr17:59412005-59997425VMP1  rs8070345G > A0.4502.20e-23C1.14D
19p13.2chr19:10523588-11047358SLC44A2  rs2288904G > A0.2301.60e-11C1.14D
19p13.2chr19:10280033-10517872TYK2  rs34536443C > G0.0501.80e-14C1.28D
19p13.3chr19:6613822-6685293TNFSF14  rs1077667G > A0.2101.70e-24C1.16D
19p13.11chr19:18080811-18300992IFI30  rs11554159G > A0.2701.90e-24C1.15D
19p13.11chr19:16328687-16640429EPS15L1  rs1870071A > G0.2902.00e-15C1.12D
19q13.33chr19:49217653-49427464DKKL1  rs8107548A > G0.2505.70e-15C1.09D
20q13.2chr20:54160302-54206301CYP24A1  rs2248359G > A0.4002.00e-13C1.08D
20q13.12chr20:45910853-46163333CD40  rs4810485C > A0.2507.70e-16C1.08D
20q13.13chr20:49790590-50046045SLC9A8  rs17785991T > A0.3504.20e-08C1.09D
20q13.33chr20:63568094-63857282SLC2A4RG  rs2256814G > A0.1903.50e-09C1.11D
22q11.21chr22:21644220-22000056MAPK1  rs2283792C > A0.4905.50e-16C1.08D

Criteria

GDXHsS00030 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date