Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

Abstract

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 × 10 11; rs10876994, P = 2.7 × 10 10; rs12368653, P = 1.0 × 10 7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 × 10 7; rs1569723, P = 2.9 × 10 7). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 × 10 184; CD58, P = 9.6 × 10 8; EVI5-RPL5, P = 2.5 × 10 6; IL2RA, P = 7.4 × 10 6; CLEC16A, P = 1.1 × 10 4; IL7R, P = 1.3 × 10 3; TYK2, P = 3.5 × 10 3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001). © 2009 Nature America, Inc. All rights reserved.