National Human Genome Research Institute

Phenotype-Genotype Integrator (PheGenI) updates: synthesizing genome-wide association study (GWAS) data with existing genomic resources
Lucia A. Hindorff, PhD, MPH1, Douglas J. Hoffman, MS2, Heather A. Junkins, MS1, Masato Kimura, PhD2, Donna Maglott, PhD2, Lon Phan, PhD2, Stephen Sherry, PhD2, Michael Feolo, MS2, Erin M. Ramos, PhD, MPH1
1

NHGRI, NIH, Bethesda, MD; 2 NCBI, NIH, Bethesda, MD

Figure 3. PheGenI Search Interface & Results Summary Figure 5. Genome View and Browser Figure 7. SNP Table

Abstract
Rapidly accumulating data from genome-wide association studies (GWAS) are most useful when synthesized with existing databases. We developed and updated the PhenotypeGenotype Integrator (PheGenI), integrating NCBI genomic databases with association data from the NHGRI GWAS Catalog. Integrating over 66,000* association records with extensive SNP, gene, and eQTL data, PheGenI enables deeper investigation of SNPs associated with a wide range of traits, facilitating the examination of the relationships between SNPs and human disease.
* Updated

Background / Rationale
GWAS have identified >8,700 genetic variants associated with a range of human traits and diseases at p<10-5 (3,716 at p < 5 x 10-8) Replication, fine mapping and follow up studies are crucial next steps to understanding functional consequences of these variants Integration of GWAS data with existing complementary databases can inform prioritization of variants to follow up, study design considerations, and generation of biological hypotheses

Figure 1. Databases and Record Counts

NHGRI GWAS Catalog N = 11,781

dbGaP
N = 54,282

dbSNP
N = 63,222,716

Gene
N = 23,550

eQTL
N = 60,657

Genetic Association Results

Genomic Variation

Genes

mRNA Expression

Figure 2. Phenotype Distribution of PheGenI SNPs Figure 8. eQTL Data and GWAS datasets

Data Sources
PheGenI merges data from the NHGRI GWAS catalog with several resources housed at NCBI (Figure 1).
http://www.genome.gov/gwastudies/ http://www.ncbi.nlm.nih.gov/projects/gapplusprev/sgap_plus.htm http://www.ncbi.nlm.nih.gov/gene/ http://www.ncbi.nlm.nih.gov/projects/SNP/ http://www.ncbi.nlm.nih.gov/gap http://www.ncbi.nlm.nih.gov/gtex/GTEX2/gtex.cgi Users may search on phenotype (broad categories or one or more traits), gene, SNP, or chromosomal range. Additional filters on for p-value or SNP functional class are available (Fig. 3). A PheGenI search of the example trait celiac disease returned several records (summarized in Fig. 3 and shown in detail in Fig. 4-8). The Genome View maps SNPs and genes to a genomic region and allows for interactive browsing and pinning of individual results (Fig. 5).

as of 3/7/2013

Figure 6. Gene Table

Where available, links are shown to eQTL data & dbGaP datasets for which GWAS data are available for request (Fig. 8).

URL:

http://www.ncbi.nlm.nih.gov/ gap/PheGenI

The association records span a broad range of human phenotypes and diseases (Figure 2). Counts are current as of 3/7/2013.

Conclusions and Future Improvements

By providing a user-friendly web interface that integrates various NCBI genomic databases with association data from the NHGRI GWAS Catalog, PheGenI enables deeper investigation and interrogation of SNPs associated with a wide range of traits, facilitating the examination of the relationships between SNPs and human disease. Future improvements to PheGenI include Annotation of supporting results Enhanced mapping of phenotype terms Incorporation of additional data, such as functional and regulatory elements.

Figure 4. Association Results Table User customizability and support

Downloadable results tables and high-resolution ideogram Ability to dynamically sort tables Most data points hyperlinked to underlying databases Interactive genome browser with customizable tracks Links to related GWAS datasets available for request YouTube tutorial (http://bit.ly/WeqNKd) Information buttons for documentation

NATIONAL HUMAN GENOME RESEARCH INSTITUTE Division of Intramural Research

Results are shown in the context of the GWAS association (Fig. 4) and linked to additional information based on gene (Figure 6) and SNP (Figure 7).

Ability to programmatically retrieve data using the NCBI Entrez Programming Utilities