GWAS meta-analysis and gene expression data link reproductive tract development, immune response and cellular proliferation/apoptosis with cervical cancer and clarify overlap with other cervical phenotypes
Koel, M.; Vosa, U.; Lepamets, M.; Laivuori, H.; Lemmelä, S.; Daly, M. J.; Estonian Biobank Research Team, ; FinnGen, ; Palta, P.; Mägi, R.; Laisk, T.
Show abstract
Genome-wide association studies (GWAS) have successfully identified associations for cervical cancer, but the underlying mechanisms of cervical biology and pathology remain uncharacterised. Our GWAS meta-analyses fill this gap, as we characterise the genetic architecture of cervical phenotypes, including up to 9,229 cases and 490,304 controls for cervical cancer from diverse ancestries. We prioritise PAX8/PAX8-AS1, LINC00339, CDC42, CLPTM1L, HLA-DRB1, and GSDMB as the most likely candidate genes for cervical cancer signals, providing insights into cervical cancer pathogenesis and supporting the involvement of reproductive tract development, immune response, and cellular proliferation/apoptosis. We construct a GRS that associates with cervical cancer (HR=3.7 for top 5% vs lowest 5%), and with other HPV- and immune-system related diagnoses in a PheWAS analysis. Our results propose valuable leads for further functional studies and the presented GRS offers an additional opportunity for risk stratification together with conventional screening strategies.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Risk factors for eight common cancers revealed from a phenome-wide Mendelian randomisation analysis of 378,142 cases and 485,715 controls 95%
- A multi-phenotype analysis reveals 19 novel susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma 95%
- Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes 95%
Similar papers in this journal
- Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants 95%
- Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses 95%
- Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility 95%
Similar papers in this journal
- A joint transcriptome-wide association study across multiple tissues identifies new candidate susceptibility genes for breast cancer 95%
- The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data 95%
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity 95%
Similar papers in this journal
- An expanded analysis framework for multivariate GWAS connects inflammatory biomarkers to functional variants and disease 96%
- Clinical case study meets population cohort: Identification of a BRCA1 pathogenic founder variant in Orcadians 95%
- Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk 93%
Similar papers in this journal
- Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits 95%
- Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways 94%
- A Comprehensive Epithelial Tubo-Ovarian Cancer Risk Prediction Model Incorporating Genetic and Epidemiological Risk Factors 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.