PLOS Genetics study maps localised shared polygenic risk across 16 cancer types

A study published in PLOS Genetics (DOI: 10.1371/journal.pgen.1012308) by Jiaqi Hu, Maiyier Muheyati, Leqi Xu, Andrew DeWan, and Hongyu Zhao investigates the extent to which genetic susceptibility to cancer is shared across tumour types, and whether any sharing is distributed randomly or converges at specific genomic regions or functional loci.

Using SUPERGNOVA to estimate pairwise local genetic correlations across 16 specific cancers and a pan-cancer phenotype, the team found that shared polygenic risk is not spread uniformly across the genome. Instead, it shows structured regional convergence that is not apparent from genome-wide analyses alone. The researchers integrated these local correlation findings with cross-cancer polygenic risk score (PRS) associations to characterise where and how shared susceptibility manifests.

The work advances understanding of the genetic architecture of cancer risk and may inform future research into shared biological pathways — such as DNA repair, cell-cycle control, or immune regulation — that underpin susceptibility to multiple cancer types. As an analytical and epidemiological study, it does not alter clinical guidance on cancer screening or risk assessment. Results represent illustrative findings from published statistical models, not individually actionable risk estimates.