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


BACKGROUND
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.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri 63110, USA. ssaccone@wustl.edu
Scott F
SF
Saccone
Nancy L
NL
Saccone
Gary E
GE
Swan
Pamela A F
PA
Madden
Alison M
AM
Goate
John P
JP
Rice
Laura J
LJ
Bierut
D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D014029:Tobacco Use Disorder / Q000235:genetics*