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

Motivation: A challenging problem after a genome-wide association study (GWAS) is to balance the statistical evidence of genotypephenotype 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 genotypephenotype 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.