articleScienceMay 4, 2023GREEN OA

Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens

JMJohn MorrisCMChristina M. CaragineZDZharko DaniloskiJDJúlia DomingoTBTimothy Barry

New York Genome Center · New York University · +3 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, and single-cell transcriptomic and proteomic sequencing, we discovered 124 cis -target genes of 91 noncoding blood trait GWAS loci. Using precise variant insertion through base editing, we connected specific variants with gene expression changes. We also identified trans -effect networks of noncoding loci when cis target genes encoded transcription factors or microRNAs. Networks were themselves enriched for GWAS variants and demonstrated polygenic…

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195
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30.28
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100%
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Authors

16

Topics & keywords

Topics
Keywords
  • Biology
  • Genome-wide association study
  • Genetics
  • Gene
  • Computational biology
  • Genome
  • CRISPR
  • Genomics
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