RT Journal Article
SR Electronic
T1 GenoWAP: Post-GWAS Prioritization Through Integrated Analysis of Genomic Functional Annotation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 019539
DO 10.1101/019539
A1 Qiongshi Lu
A1 Xinwei Yao
A1 Yiming Hu
A1 Hongyu Zhao
YR 2015
UL http://biorxiv.org/content/early/2015/05/20/019539.abstract
AB Motivation Genome-wide association study (GWAS) has been a great success in the past decade. However, significant challenges still remain in both identifying new risk loci and interpreting results. Bonferroni-corrected significance level is known to be conservative, leading to insufficient statistical power when the effect size is moderate at risk locus. Complex structure of linkage disequilibrium also makes it challenging to separate causal variants from nonfunctional ones in large haplotype blocks.Results We describe GenoWAP, a post-GWAS prioritization method that integrates genomic functional annotation and GWAS test statistics. The effectiveness of GenoWAP is demonstrated through its applications to Crohn’s disease and schizophrenia using the largest studies available, where highly ranked loci show substantially stronger signals in the whole dataset after prioritization based on a subset of samples. At the single nucleotide polymorphism (SNP) level, top ranked SNPs after prioritization have both higher replication rates and consistently stronger enrichment of eQTLs. Within each risk locus, GenoWAP is also able to distinguish functional sites from groups of correlated SNPs.Availability and Implementation GenoWAP is freely available on the web at http://genocanyon.med.yale.edu/GenoWAP