2026-10-07T20:38:22Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34014657 2026-09-30T14:08:54Z category_24202 item_type_3 month_year_09_2026

gene burden and single-variant test for CORGI2 and NGLR cases along with genotype report. dhruva gadani (25122966) Statistical and quantitative genetics early onset colorectal cancer Genetic variant information <p dir="ltr">Early-Onset Colorectal Cancer (EOCRC) is colorectal cancer (CRC) diagnosed before age 50. The incidence of EOCRC is increasing in most countries. It is still rare compared to average-onset CRC, making identification of the causes challenging. Whilst not the cause of the increase in incidence, a significant proportion (15-25%) of EOCRC cases have a known hereditary syndrome or a strong family history but no pathogenic variant.</p><p dir="ltr">To identify novel variants associated with EOCRC, I identified likely pathogenic (LP) missense (REVEL score >= 0.5) or loss-of-function variants from 115 EOCRC cases from CORGI. I identified 1149 genes with one or more qualifying variants, 10 of which also had a LP variant in an independent cohort of EOCRC cases (SCOTTY). For further validation and to enable gene burden and single-variant analysis, I sourced controls and additional EOCRC cases from the National Genomic Research Library. I identified variants in 3 genes that were enriched in EOCRC cases: PMS2, DNAH2, and FLG. PMS2 is a known CRC gene, but DNAH2 and FLG are novel. I determined whether the PMS2 or DNAH2 variants were present in an additional 94 DNA samples from EOCRC patients from CORGI2.</p> 2026-09-30T14:08:54Z Dataset Dataset 10.6084/m9.figshare.34014657.v2 https://figshare.com/articles/dataset/gene_burden_and_single-variant_test_for_CORGI2_and_NGLR_cases_along_with_genotype_report_/34014657 CC BY 4.0