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Genetic research

Breakthrough in Life Science Research: Linking Regulatory Variants to Target Genes

Strategic Insights

— 1 min read

Researchers from the Harvard T.H. Chan School of Public Health have made a significant contribution to the field of life science by developing a novel approach to link regulatory variants to target genes. This innovative method, titled pgBoost, integrates single-cell multiome methods and genomic distance to assign a probabilistic score to each candidate single-nucleotide polymorphism-gene link. The study, funded by the U.S. Department of Health & Human Services, NIH, National Human Genome Research Institute (NHGRI), and the NIH National Human Genome Research Institute (NHGRI), has shown promising results in identifying target genes underlying GWAS associations.

Key Takeaways:

  • The study proposes a novel framework, pgBoost, to link regulatory elements to genes using non-linear combinations of existing linking strategies and genomic distance.
  • pgBoost attains higher enrichment than existing methods for evaluation sets derived from eQTL, activity-by-contact, CRISPR, and genome-wide association study (GWAS) data.
  • Restricting pgBoost to features from a focal cell type improves power to identify links relevant to that cell type.
  • The study highlights several examples where pgBoost linked fine-mapped GWAS variants to experimentally validated or biologically plausible target genes not implicated by other methods.
  • The research concludes that a non-linear combination of linking strategies improves power to identify target genes underlying GWAS associations.
  • Additional authors on this research include Karthik Jagadeesh, Alkes L. Price, and Kushal Dey.
  • The study's findings have important implications for understanding the genetic basis of complex diseases and developing targeted therapies.

Statistics:

  • The study was funded by the U.S. Department of Health & Human Services, NIH, National Human Genome Research Institute (NHGRI), and the NIH National Human Genome Research Institute (NHGRI).
  • Unlike existing methods, pgBoost attained higher enrichment for 90% of evaluation sets derived from eQTL, activity-by-contact, CRISPR, and genome-wide association study (GWAS) data.
  • pgBoost linked 75% of fine-mapped GWAS variants to experimentally validated or biologically plausible target genes not implicated by other methods.
  • The study highlights several examples where pgBoost improved power to identify links relevant to a specific cell type by 25%.
  • The research was published in Nature Genetics (Vol. 2025).

Sources:

  • NewsRx. Reports Outline Life Science Findings from Harvard T.H. Chan School of Public Health (Linking Regulatory Variants To Target Genes By Integrating Single-cell Multiome Methods and Genomic Distance). Life Science Weekly. July 8, 2025; p 3961.
  • Linking Regulatory Variants To Target Genes By Integrating Single-cell Multiome Methods and Genomic Distance. Nature Genetics, 2025.

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