A meta-analyis comprising 7 datasets of non-overlapping subjects of European descent involving 5,545 individuals with with Multiple Sclerosis (MS) and 12,153 controls using Affy 500K, Illumina 550 , Illumina Infinium and Hap370CNV genotpying platforms.  A total of 2,529,394 unique SNPs were analysed on at least 2 datasets.  To maximise genome-wide coverage, the MACH algorithm was used to impute 2.5M SNPs using the HapMap Phase II data across the genome in all datasets.  Association at genome-wide significance (P<5x10-8) was observed for 3 novel, as well as confirming 6 previously published, loci.  Ten further susceptibility loci had a suggestitive P<1x10-6, and some of these loci have evidence of association in other inflammatory diseases.

Study Type
Whole Genome Association Study
Exclusion Criteria

Samples were excluded due to:-

  • genotype call rate <95%
  • sex/gender discordance
  • excess heterozygosity

Markers were excluded due to:-

  • Hardy-Weinberg equilibrium p<10-6
  • minor allele frequency (MAF) <1%
  • genotype call rate <95%

EIGENSOFT was used to calculate the dominant ten eigenvectors within each stratum, and subsequently remove outliers in terms of genetic ancestry.

All datasets were imputed using the MACH algorithm using the 120 phased chromosomes from the CEU samples in HapMap Phase II as the reference. After imputation all SNPs with an imputation quality score less or equal than 0.10 or MAF<0.01 per stratum were excluded.

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.1chr1:116487687-116569937CD58  rs2300747A > G0.0906.46e-09D1.37D
1p36.22chr1:9915143-10573188KIF1B  rs10492972T > C0.3202.43e-01D1.04D
1q31.2chr1:192500477-192578911RGS1  rs2760524G > A0.1703.00e-04D1.14D
1q32.1chr1:200893429-201070752KIF21B  rs12122721G > A0.2802.43e-03D1.1D
2p13.3chr2:68309121-68631186FBXO48  PLEK  APLF  rs7592330A > G0.4402.42e-07D1.15D
2p21chr2:43082854-43135241THADA  rs6718520G > A0.4803.42e-08D1.17D
3p24.1chr3:27999281-28088981EOMES  rs170934C > T0.4801.57e-08D1.17D
3q13.11chr3:105653463-105954342CBLB  rs9846534T > C0.1904.34e-01D1.03D
3q13.33chr3:121849748-122126077CD86  ILDR1  rs2681424C > T0.4002.33e-07D1.16D
3q13.33chr3:119383611-119581808TMEM39A  rs1132200C > T0.1503.67e-03D1.11D
3q25.33chr3:159886425-160033824IL12A  rs4680534T > C0.3703.28e-05D1.12D
5p13.2chr5:35795636-36035028IL7R  rs6897932C > T0.2602.26e-04D1.12D
5p15.32chr5:4673722-4801883rs1393122A > G0.1602.87e-01D1.04D
5q33.3chr5:159403811-159521954IL12B  rs10866713G > A0.2206.57e-07D1.17D
5q33.3chr5:159091760-159399302IL12B  rs2546890A > G0.4807.95e-08D1.16D
6q25.3chr6:158897742-159119181TAGAP  rs1738074C > T0.4203.72e-07D1.15D
9p24.1chr9:5796779-6145022MLANA  rs2150702A > G0.4903.28e-08D1.16D
10p15.1chr10:5988280-6131453IL2RA  rs12722489C > T0.1503.66e-08D1.23D
10p15.1chr10:5988280-6134149IL2RA  rs7089861C > G0.2703.84e-08D1.19D
10q22.3chr10:79237086-79312766ZMIZ1  rs1250542G > A0.3703.97e-07D1.15D
11q12.2chr11:60958137-61068645CD6  rs17824933C > G0.2603.38e-05D1.14D
12p13.31chr12:6312329-6354696TNFRSF1A  rs1800693T > C0.4201.41e-05D1.14D
12q14.1chr12:57576969-58094884METTL1  rs703842A > G0.3101.72e-05D1.14D
12q24.31chr12:122900896-123523526MPHOSPH9  rs1790100T > G0.2306.61e-04D1.11D
13q14.2chr13:50160568-50494569rs9596270T > C0.0707.00e-07D1.35D
16p13.13chr16:11213167-11384988RMI2  PRM3  TNP2  PRM1  PRM2  rs7191700C > T0.3306.40e-07D1.15D
16p13.13chr16:10923201-11218316CLEC16A  rs12708716A > G0.3501.08e-04D1.11D
16q24.1chr16:85956661-85990498IRF8  rs17445836G > A0.2205.30e-03D1.1D
17q21.2chr17:42142007-42774617STAT3  rs2293152C > G0.3804.09e-08D1.22D
17q21.2chr17:42156716-42774617STAT3  rs744166A > G0.4306.35e-06D1.13D
17q21.32chr17:47232327-47798656KPNB1  TBX21  TBKBP1  rs8070463T > C0.5009.55e-08D1.15D
18q22.2chr18:69831437-69902924CD226  rs763361C > T0.4804.50e-02D1.06D
19p13.11chr19:16332414-16643969EPS15L1  rs10411936G > A0.3002.04e-07D1.16D
20q13.12chr20:45906223-46158839CD40  rs6074022T > C0.2704.91e-06D1.15D
MHCchr6:29866695-30096785HLA-B  rs9260489G > T0.4501.16e-11D1.21D
MHCchr6:32371209-32682835HLA-DRB1  rs3129889A > G0.2001.03e-206D2.97D


GDXHsS00041 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date