FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases

• Published in: Genome Biology Vol. 25; no. 1; p. 3
• Main Authors: Breeze, Charles E., Haugen, Eric, Gutierrez-Arcelus, María, Yao, Xiaozheng, Teschendorff, Andrew, Beck, Stephan, Dunham, Ian, Stamatoyannopoulos, John, Franceschini, Nora, Machiela, Mitchell J., Berndt, Sonja I.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 02.01.2024; BMC
• Subjects: Animal Genetics and Genomics; Annotations; Bioinformatics; Biomedical and Life Sciences; Consortia; data collection; Datasets; Evolutionary Biology; Expression quantitative trait locus (eQTL); Functional annotation; Gene expression; Gene loci; Gene regulation; genes; Genome-wide association studies; Genome-Wide Association Study; Genome-wide association study (GWAS); Genomes; Human Genetics; Internet; Life Sciences; Method; Microbial Genetics and Genomics; Plant Genetics and Genomics; Polymorphism, Single Nucleotide; Protein Binding; Regulatory elements; Regulatory sequences; Regulatory Sequences, Nucleic Acid; Transcription factors; Variant scoring; Expression quantitative trait locus (eQTL); Genome-wide association study (GWAS); DNase-seq; Transcription factor (TF); Variant scoring; Massively parallel reporter assay (MPRA); Gene regulation; Single guide RNA (sgRNA); Activity-by-contact (ABC); Functional annotation; CRISPR (clustered regularly interspaced short palindromic repeats); Regulatory elements
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-023-03126-1

The majority of disease-associated variants identified through genome-wide association studies are located outside of protein-coding regions. Prioritizing candidate regulatory variants and gene targets to identify potential biological mechanisms for further functional experiments can be challenging. To address this challenge, we developed FORGEdb ( https://forgedb.cancer.gov/ ; https://forge2.altiusinstitute.org/files/forgedb.html ; and https://doi.org/10.5281/zenodo.10067458 ), a standalone and web-based tool that integrates multiple datasets, delivering information on associated regulatory elements, transcription factor binding sites, and target genes for over 37 million variants. FORGEdb scores provide researchers with a quantitative assessment of the relative importance of each variant for targeted functional experiments.