Publications by authors named "Matthew Welland"
Purpose: As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.
Methods: Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (, , , ) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants.
Article Synopsis
- About 25% of patients with unexplained kidney failure have a genetic cause, specifically related to monogenic disorders.
- A study explored the effectiveness of whole genome sequencing (WGS) combined with broad gene panel analysis in diagnosing these cases, finding it to be a viable method for identifying genetic mutations.
- Among 100 participants aged ≤50 with stage 5 chronic kidney disease, a genetic diagnosis was reached in 25%, with a higher likelihood of positive results in those with a family history of chronic kidney disease.
100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.
N Engl J Med
November 2021
Background: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.
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