A feasibility study of whole genome germline testing as an adjunct screening tool in a UK general private practice
Whole genome sequencing (WGS) presents an opportunity to identify asymptomatic individuals at increased risk for disease. We set up a model pathway to assess the use of WGS combined with a medical assessment in primary care. We recruited 104 participants (102 unrelated) from a private general practice for a medical assessment, WGS and panel testing. WGS analysed 566 clinically actionable genes, including moderate to high-risk monogenic traits, recessive traits and pharmaco-genes. Polygenic risk scores (PRS) were calculated for 4 cancers. Twenty-three individuals (22%) had an actionable germline variant in cancer, cardiac, lipid or thromboembolic genes. Ten of these (43%) had pathogenic variants in cancer predisposition genes, 60 (58%) participants harboured recessive genetic alterations and 43 (41%) had pharmacogenetic variants. Our findings show WGS in primary care identified actionable variants in 22% of individuals resulting in a change in clinical management. Pharmacogenomics may alter prescribing in a further 41%.
Authors
- Elizabeth Bancroft (ORCID: https://orcid.org/0000-0002-5482-5660)
- Sophie Hicks
- Rosalind A. Eeles (ORCID: https://orcid.org/0000-0002-3698-6241)
- Priya Narayanan
- Tokhir Dadaev (ORCID: https://orcid.org/0000-0002-8268-0438)
- Robert Thomas (ORCID: https://orcid.org/0009-0003-8373-0518)
- Tessa Homfray (ORCID: https://orcid.org/0000-0002-9981-9678)
- Ann-Britt Jones (ORCID: https://orcid.org/0000-0001-6565-4556)
- C. Donmall Davies
- John J. Healy (ORCID: https://orcid.org/0000-0003-3075-9248)
- Lucy Side
- Zsofia Kote‐Jarai (ORCID: https://orcid.org/0000-0002-6329-5155)
- Luís Izquierdo (ORCID: https://orcid.org/0000-0002-3704-9874)
- Miriam Leon
- Bibiana Palao
- Terri Patricia McVeigh (ORCID: https://orcid.org/0000-0001-9201-9216)
- Vincenzo Cirigliano (ORCID: https://orcid.org/0000-0002-9056-754X)
- Candace L. Williams (ORCID: https://orcid.org/0000-0002-1711-1183)
- Michael A. Sandberg
- Zahir Amin
- Gabriella Pichert
- Enrique Góngora
- Elena Ordóñez
- Ghada Al Shakarchi
- Denis Pellerin
Institutions
- Royal Marsden NHS Foundation Trust (GB)
- Institute of Cancer Research (GB)
- American InterContinental University (US)
- Princess Anne Hospital (GB)
- Royal Brompton Hospital (GB)
- Centre For Human Genetics (IN)
- Universidad Intercontinental (MX)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1038/s41598-025-18183-8
- Citations
- 2
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 3.63
Funders
- Royal Marsden NHS Foundation Trust
- Cancer Research UK
- National Institute for Health and Care Research