biostudies-literatureNolan JNIHR Oxford Biomedical Research CentreNational Institute for Health Research (NIHR)Wellcome Trust101051https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617895biostudies-literatureUnknown26(3)<h4>Purpose</h4>The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs.<h4>Methods</h4>An observational study in an area representing one-fifth of England.<h4>Results</h4>Data 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, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF.<h4>Conclusion</h4>Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.Genetics in medicine : official journal of the American College of Medical GeneticsSecondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.PMC7617895NIHR203311204826Thomson KGillen DMcFarlane CCazeaux ABuchanan JBroadgate SKasperaviciute DWatson MWilliams EForrest JThomas EHaeger AJones AGeorge ECrawford GButler SLopez JTaylor JStewart HHastings Ward JThomas SLucassen AThomas TGabriel JOrmondroyd EKarpe FHoffman JBedenham TWalker SKovacs EPond EBlair ENolan JLloyd-Jani ASherman CLeigh SO'Rourke AWHawkes LHodgkiss CCranston TCraft JAlmeida JLimb EWakelin HfalseSecondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.<h4>Purpose</h4>The UK 100,000 Genomes Project offered participants screening for additional findings (AFs) in genes associated with familial hypercholesterolemia (FH) or hereditary cancer syndromes including breast/ovarian cancer (HBOC), Lynch, familial adenomatous polyposis, MYH-associated polyposis, multiple endocrine neoplasia (MEN), and von Hippel-Lindau. Here, we report disclosure processes, manifestation of AF-related disease, outcomes, and costs.<h4>Methods</h4>An observational study in an area representing one-fifth of England.<h4>Results</h4>Data 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, 4 cancer-AF recipients had evidence of disease, including 1 medullary thyroid cancer. Six women with an HBOC AF, 3 women with a Lynch syndrome AF, and 2 individuals with a MEN AF elected for risk-reducing surgery. New hyperlipidemia diagnoses were made in 6 FH-AF recipients and treatment (re-)initiated for 7 with prior hyperlipidemia. Generating and disclosing AFs in this region cost £1.4m; £8680 per clinically significant AF.<h4>Conclusion</h4>Generation and disclosure of AFs identifies individuals with and without personal or familial evidence of disease and prompts appropriate clinical interventions. Results can inform policy toward secondary findings.2024-01-01T00:00:00Z2024 Mar2026-06-15T06:12:21.574Z2025-08-23T03:09:16.155ZS-EPMC76178953813130810.1016/j.gim.2023.101051