Secondary (additional) findings from the 100,000 Genomes Project: disease manifestation, healthcare outcomes and costs of disclosure.
Nolan J., Buchanan J., Taylor J., Almeida J., Bedenham T., Blair E., Broadgate S., Butler S., Cazeaux A., Craft J., Cranston T., Crawford G., Forrest J., Gabriel J., George E., Gillen D., Haeger A., Hastings Ward J., Hawkes L., Hodgkiss C., Hoffman J., Jones A., Karpe F., Kasperaviciute D., Kovacs E., Leigh S., Limb E., Lloyd-Jani A., Lopez J., Lucassen A., McFarlane C., O'Rourke AW., Pond E., Sherman C., Stewart H., Thomas E., Thomas S., Thomas T., Thomson K., Wakelin H., Walker S., Watson M., Williams E., Ormondroyd E.
PurposeThe UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolaemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia, von Hippel-Lindau. Here we report disclosure processes, manifestation of AF-related disease, outcomes and costs.MethodsAn observational study in an area representing one-fifth of England.ResultsData were collected from 89 adult AF recipients. At disclosure, among 57 recipients of a cancer predisposition-associated AF and 32 recipients of an FH-associated AF, 35% and 88% respectively had personal and/or family history evidence of AF-related disease. During post-disclosure investigations, four cancer-AF recipients had evidence of disease, including one medullary thyroid cancer. Six women with an HBOC AF, three women with a Lynch syndrome AF, and two individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidaemia diagnoses were made in six FH-AF recipients, and treatment (re-)initiated for seven with prior hyperlipidaemia. Generating and disclosing AFs in this region cost £1.4m; £8,680 per clinically significant AF.ConclusionGeneration and disclosure of AFs identifies individuals with, and without personal or familial evidence of disease, and prompts appropriate clinical interventions. Results can inform policy towards secondary findings.