Abstract

BackgroundA number of tools for the examination of linkage disequilibrium (LD) patterns between nearby alleles exist, but none are available for quickly and easily investigating LD at longer ranges (>500 kb). We have developed a web-based query tool (GLIDERS: Genome-wide LInkage DisEquilibrium Repository and Search engine) that enables the retrieval of pairwise associations with r2 ≥ 0.3 across the human genome for any SNP genotyped within HapMap phase 2 and 3, regardless of distance between the markers.DescriptionGLIDERS is an easy to use web tool that only requires the user to enter rs numbers of SNPs they want to retrieve genome-wide LD for (both nearby and long-range). The intuitive web interface handles both manual entry of SNP IDs as well as allowing users to upload files of SNP IDs. The user can limit the resulting inter SNP associations with easy to use menu options. These include MAF limit (5-45%), distance limits between SNPs (minimum and maximum), r2 (0.3 to 1), HapMap population sample (CEU, YRI and JPT+CHB combined) and HapMap build/release. All resulting genome-wide inter-SNP associations are displayed on a single output page, which has a link to a downloadable tab delimited text file.ConclusionGLIDERS is a quick and easy way to retrieve genome-wide inter-SNP associations and to explore LD patterns for any number of SNPs of interest. GLIDERS can be useful in identifying SNPs with long-range LD. This can highlight mis-mapping or other potential association signal localisation problems.

Highlights

  • A number of tools for the examination of linkage disequilibrium (LD) patterns between nearby alleles exist, but none are available for quickly and investigating LD at longer ranges (>500 kb)

  • Analysis of HapMap has revealed wide-spread, and often complex, patterns of LD which has made the localization of causal variants difficult in regions identified to be associated with disease through genome-wide association studies (GWAS)

  • To address the need for a resource investigating long-range LD we have developed the Genome-wide LInkage DisEquilibrium Repository and Search engine (GLIDERS)

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Summary

Conclusion

With the large number of GWAS being carried out and the large number of SNPs showing disease association, it is important to be able to check quickly and for distant SNP proxies which might affect disease gene localization. GLIDERS is an ideal utility for this as it contains all genome-wide inter-SNP associations between HapMap markers from the three main population samples calculated using both phase 2 and phase 3 genotypes. GLIDERS is an easy to use inter-SNP association web database tool that can be used by any researcher with internet access. GWAS: (genome-wide association study); LD: (linkage disequilibrium); MAF: (minor allele frequency); SNP: (single nucleotide polymorphism); GLIDERS: (Genomewide LInkage DisEquilibrium Repository and Search engine); CEU: (CEPH (Utah residents with ancestry from northern and western Europe)); YRI: (Yoruba in Ibadan, Nigeria); JPT: (Japanese in Tokyo, Japan); CHB: (Han Chinese in Beijing, China); CGI: (Common Gateway Interface); SNAP: (SNP Annotation and Proxy Search); rsID: (reference SNP identification); QC: (quality control); Kb: (kilobase). RL carried out LD calculations, developed the database and drafted the manuscript. LC contributed to database design and supervised the project.

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