Researchers at New York University and the New York Genome Center have developed STING-seq (Systematic Targeting and Inhibition of Noncoding GWAS loci with single-cell sequencing), a new approach combining genetic association studies, gene editing, and single-cell sequencing to connect genetic variants to human traits and health. This approach, published in Science, aims to identify causal variants and genes for blood cell traits and help scientists identify drug targets for genetic-based diseases.
Genome-wide association studies have been an essential tool for studying the human genome, but they have been challenging to extract biological mechanisms and inform drug targets for diseases from massive data sets. One complication is that many variants are found close to each other within the genome and travel together through generations, a concept called linkage.
The researchers used STING-seq to uncover target genes of noncoding variants for blood traits, which are easy to measure in routine blood tests and have been well-studied in GWAS. Blood traits have been identified as a promising target since they are easily measurable and have been studied in GWAS.
Once the researchers identified 543 candidate regions of the genome that may play a role in blood traits, they used CRISPR inhibition to silence precise regions of the genome. Then, the team looked at the expression of nearby genes in individual cells to see if particular genes were turned on or off.
“The power of STING-seq is we could apply this approach to any disease or trait,” says first author John Morris, a postdoctoral associate at the New York Genome Center and NYU.
STING-seq offers a new strategy to directly connect genetic variants to human traits and can aid researchers in identifying drug targets for diseases with a genetic basis. Study co-author Tuuli Lappalainen, senior associate faculty member at the New York Genome Center and professor of genomics at the KTH Royal Institute of Technology in Sweden, explains, “Now that we can connect noncoding variants to target genes, this gives us evidence that either small molecules or antibody therapies could be developed to change the expression of specific genes.”