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Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence.


ABSTRACT:

Motivation

A challenging problem after a genome-wide association study (GWAS) is to balance the statistical evidence of genotype-phenotype correlation with a priori evidence of biological relevance.

Results

We introduce a method for systematically prioritizing single nucleotide polymorphisms (SNPs) for further study after a GWAS. The method combines evidence across multiple domains including statistical evidence of genotype-phenotype correlation, known pathways in the pathologic development of disease, SNP/gene functional properties, comparative genomics, prior evidence of genetic linkage, and linkage disequilibrium. We apply this method to a GWAS of nicotine dependence, and use simulated data to test it on several commercial SNP microarrays.

Availability

A comprehensive database of biological prioritization scores for all known SNPs is available at http://zork.wustl.edu/gin. This can be used to prioritize nicotine dependence association studies through a straightforward mathematical formula-no special software is necessary.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Saccone SF 

PROVIDER: S-EPMC2610477 | biostudies-literature |

REPOSITORIES: biostudies-literature

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