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Bioinformatics Advance Access originally published online on June 19, 2008
Bioinformatics 2008 24(16):1805-1811; doi:10.1093/bioinformatics/btn315
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Scott F. Saccone 1,*, Nancy L. Saccone 2, Gary E. Swan 3, Pamela A. F. Madden 1, Alison M. Goate 1,2, John P. Rice 1,2 and Laura J. Bierut 1

1Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 South Euclid Avenue, 2Department of Genetics, Washington University School of Medicine, Campus Box 8232, 4566 Scott Avenue, Saint Louis, Missouri, 63110 and 3Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, California, 94025, USA

*To whom correspondence should be addressed.


  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.

Contact: ssaccone{at}wustl.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Martin Bishop

Received on May 1, 2008; revised on June 10, 2008; accepted on June 16, 2008

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