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RWAS

Summary Table

NAME CITATION YEAR
RWAS Grishin D, Gusev A. (2022) Allelic imbalance of chromatin accessibility in cancer identifies candidate causal risk variants and their mechanisms Nat. Genet., 54 (6) 837-849. doi:10.1038/s41588-022-01075-2. PMID 35697866 2022

RWAS

  • NAME : RWAS
  • SHORT NAME : RWAS
  • FULL NAME : Regulome-Wide Association Study
  • URL : http://gusevlab.org/projects/fusion/#tcga-regulome-wide-association-study-rwas-atac-seq-models
  • TITLE : Allelic imbalance of chromatin accessibility in cancer identifies candidate causal risk variants and their mechanisms
  • DOI : 10.1038/s41588-022-01075-2
  • ABSTRACT : While many germline cancer risk variants have been identified through genome-wide association studies (GWAS), the mechanisms by which these variants operate remain largely unknown. Here we used 406 cancer ATAC-Seq samples across 23 cancer types to identify 7,262 germline allele-specific accessibility QTLs (as-aQTLs). Cancer as-aQTLs had stronger enrichment for cancer risk heritability (up to 145 fold) than any other functional annotation across seven cancer GWAS. Most cancer as-aQTLs directly altered transcription factor (TF) motifs and exhibited differential TF binding and gene expression in functional screens. To connect as-aQTLs to putative risk mechanisms, we introduced the regulome-wide associations study (RWAS). RWAS identified genetically associated accessible peaks at >70% of known breast and prostate loci and discovered new risk loci in all examined cancer types. Integrating as-aQTL discovery, motif analysis and RWAS identified candidate causal regulatory elements and their probable upstream regulators. Our work establishes cancer as-aQTLs and RWAS analysis as powerful tools to study the genetic architecture of cancer risk.
  • CITATION : Grishin D, Gusev A. (2022) Allelic imbalance of chromatin accessibility in cancer identifies candidate causal risk variants and their mechanisms Nat. Genet., 54 (6) 837-849. doi:10.1038/s41588-022-01075-2. PMID 35697866
  • JOURNAL_INFO : Nature genetics ; Nat. Genet. ; 2022 ; 54 ; 6 ; 837-849
  • PUBMED_LINK : 35697866