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%.