Phenome-wide scan for traits associated with polygenic risk scores (PRSs) for childhood cancer
Approved Research ID: 89902
Approval date: September 9th 2022
Genetic variation associated with childhood cancer may contribute to risk for certain traits in adulthood. However, the shared genetic basis between childhood cancer and traits in adulthood remains largely unknown. Thus, the objective of our research is to conduct a scan for all adult traits associated with polygenic risk scores (PRSs) for childhood acute lymphoblastic leukemia (ALL), neuroblastoma, and Ewing sarcoma. A PRS is an assessment of the risk of a specific disease or condition based on the collective influence of many genetic variants.
We will first curate a list of the most common type of genetic variant (i.e., single nucleotide polymorphisms, or SNPs) related to these childhood cancers by risk group or subtype by reviewing the NHGRI-EBI Genome-wide association studies (GWAS) Catalog and previously published GWAS. The SNPs will be queried through the UK Biobank (UKBB) data. The PRSs for each childhood cancer type and subtype will then be computed via a standard method. Next, a scan will be performed to examine the association between each childhood cancer PRS and each adult trait. We will apply the same approach to investigate the relationship between PRSs for childhood cancers and adult traits among minority populations, where possible.
With our proposed research, we expect to shed light on the shared genetic architecture between childhood cancer and traits in adulthood. Furthermore, even though the populations of the UKBB and prior GWAS are not very diverse, it is worth investigating whether traits associated with each PRS differ by race/ethnicity. And finally, our study may contribute to the identification of the biological mechanisms that cause childhood cancer, and this knowledge may lead to new targets for cancer treatment.