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ABN Autumn Scientific Meeting

In a systematic genome-wide analysis of multiple sclerosis involving 12 360 individuals we identified three markers showing association with genome-wide significance (p.5.0E–7); one from IL7R gene (rs6897932) and two from the IL2RA gene (rs12722489/rs2104286). In each case the major allele modestly increases susceptibility to the disease (odds ratio ,1.2). To replicate and refine these associations we typed all three variants in an additional 20 708 individuals from Caucasian populations within the IMSGC providing a total of 33,068 individuals for analysis (11 019 unrelated cases, 13 616 controls and 2811 trios giving 8433 individuals). All three associations were confirmed at high levels of significance (rs6897932 p = 1.21E–17; rs2104286 p = 2.38E–23; rs12722489 p = 2.24E–15) and we found no evidence for heterogeneity of effect across the populations studied. Analysis at a genotypic level confirmed homozygosity for the risk allele conferred greater susceptibility than the heterozygote genotype. This extension analysis illustrates the value of data sets that are significantly larger than the 2000 cases and controls recommended as a minimum by the Wellcome Trust Case Control Consortium (WTCCC); and convincingly replicates the associations in the IL7R and IL2RA genes.