Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms - PubMed (original) (raw)

Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms

Manuel Comabella et al. PLoS One. 2008.

Abstract

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Graphs showing physical position of SNP rs3129934 on chromosome 6.

SNP rs3129934, which showed the strongest association with the disease in the Spanish and US replication cohorts, is located approximately 200 kb from the HLA-DRB1 locus.

Figure 2

Figure 2. Graph illustrating genes located in proximity to SNPs rs1327328 and rs7326018 on chromosome 13.

SNP rs1327328 was the second most significant SNP validated in the Spanish and US replication cohorts, and is in strong linkage disequilibrium with SNP rs7326018. SNPs rs1330943, rs9588771, rs6492466, rs9583760, rs4284505, and rs9589207 have been typed by HapMap.

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