You may have heard of genomewide association studies (GWAS), which discover genetic variants associated with disease. Phenome-wide association studies (PheWAS) flip the analysis and discover diseases or traits (i.e. phenotypes) associated with genetic variation. A team of researchers from the University of Minnesota, Drs. Eun Mi Jung, Andrew Raduski, Lauren Mills, and Logan Spector, recently published an article on a phenotype-wide association study looking at genetic traits of British adults and children.
Previous GWAS have shown that many genes are related to a higher risk of cancers for children, especially for cancers like acute lymphoblastic leukemia (ALL), neuroblastoma (NB), and Ewing sarcoma (ES). The team used genetic and phenotype data on a large population of adults and children from the UK Biobank Study. They aimed to see if certain clinical diagnoses in adults (i.e., phenotypes) were related to any genetic risk for the three childhood cancers listed above.
For analysis, the team compared both individual single nucleotide polymorphisms (SNPs) and overall polygenic risk scores (PRS), an estimate of a person’s disease risk that is due to their genetics, for the cancers with various health issues found in adults. They found that childhood ALL PRS and ALL in adults were significantly positively related compared to the ALL risk for control adults (see Figure 1). Additionally, high-risk neuroblastoma PRS in children was significantly associated with adult nonrheumatic aortic valve disorders. There were no associations found between childhood Ewing sarcoma and adult phenotypes. Comparing individual SNPs with phenotypes showed that three SNPs in ALL were associated with increased risk of ALL and atrioventricular block and decreased risk of electrolyte imbalance and skin cancer. No significant associations were found for SNPs associated with neuroblastoma or Ewing sarcoma.
The results from this study show that children with genetic risk of ALL may have a lifelong risk of developing ALL. Furthermore, those with a genetic risk of high-risk neuroblastoma may be more likely to develop circulatory diseases. The researchers state that more research is needed to evaluate the relationship between having genetic risk for childhood cancers and risk for adult diseases. CLIC partners around the world are studying childhood cancer SNPs and PRS, and hope to use this data to build a complete list of SNP and an accurate PRS for diverse populations of children. With the data resource built during our CLIC Genomics Project, we hope to contribute to more studies that examine the implications of having genetic predisposition for childhood cancer.
Citation:
Article Title: A phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank.
Authors: Jung EM, Raduski AR, Mills LJ, Spector LG.
Published In: HGG Adv. 2025 Jan 9;6(1):100356. doi: 10.1016/j.xhgg.2024.100356. Epub 2024 Sep 26. PMID: 39340156; PMCID: PMC11538869.