Systematic Biological Prioritization After a Genome-Wide Association Study: an Application to Nicotine Dependence


Saccone, S. F., Saccone, N. L., Swan, G. E., Madden, P. A., Goate, A. M., Rice, J. P., & Bierut, L. J. (2008). Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence. Bioinformatics, 24(16), 1805-1811.



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.


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.


A comprehensive database of biological prioritization scores for all known SNPs is available at This can be used to prioritize nicotine dependence association studies through a straightforward mathematical formula—no special software is necessary.

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