GWAS-identified multiple sclerosis risk loci involved in immune response: Validation in Russians

• We performed a replication study of 9 GWAS-identified SNPs with MS in Russians.
• We validated associations of rs6498169 and rs2104286 with MS.
• Associations of rs6498169 and rs17445836 with MS were observed in women.
• Associations of rs6897932 and rs2300747 with MS were observed in men.
• We identified two protective biallelic combinations in women. Both include rs1800693.

Multiple sclerosis (MS) is a chronic neuro-inflammatory disease of complex etiology. The results of GWAS, a high-throughput method to discover genetic architectureof MS, require replication in independent ethnic groups. We performed a replication study of nine GWAS-identified SNPs in immune response in Russians. Associations of CLEC16A and IL2RA with MS were validated. Besides, we observed the associations of CLEC16A and IRF8 in women, and IL7RA and CD58 in men. With multi-locus association analysis two protective biallelic combinations: (TNFRSF1A*T + CLEC16A*A) and (TNFRSF1A*T + IRF8*A) were identified in women. Associations of CLEC16A*G/G and both biallelic combinations in women with MS survived the permutation test.