Ontology highlight
ABSTRACT: Purpose
To measure the prevalence of medically actionable pathogenic variants (PVs) among a population of healthy elderly individuals.Methods
We used targeted sequencing to detect pathogenic or likely pathogenic variants in 55 genes associated with autosomal dominant medically actionable conditions, among a population of 13,131 individuals aged 70 or older (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Participants had no previous diagnosis or current symptoms of cardiovascular disease, physical disability or dementia, and no current diagnosis of life-threatening cancer. Variant curation followed American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) standards.Results
One in 75 (1.3%) healthy elderly individuals carried a PV. This was lower than rates reported from population-based studies, which have ranged from 1.8% to 3.4%. We detected 20 PV carriers for Lynch syndrome (MSH6/MLH1/MSH2/PMS2) and 13 for familial hypercholesterolemia (LDLR/APOB/PCSK9). Among 7056 female participants, we detected 15 BRCA1/BRCA2 PV carriers (1 in 470 females). We detected 86 carriers of PVs in lower-penetrance genes associated with inherited cardiac disorders.Conclusion
Medically actionable PVs are carried in a healthy elderly population. Our findings raise questions about the actionability of lower-penetrance genes, especially when PVs are detected in the absence of symptoms and/or family history of disease.
SUBMITTER: Lacaze P
PROVIDER: S-EPMC7606791 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Lacaze Paul P Sebra Robert R Riaz Moeen M Tiller Jane J Revote Jerico J Phung James J Parker Emily J EJ Orchard Suzanne G SG Lockery Jessica E JE Wolfe Rory R Strahl Maya M Wang Ying C YC Chen Rong R Sisco Daniel D Arnold Todd T Thompson Bryony A BA Buchanan Daniel D DD Macrae Finlay A FA James Paul A PA Abhayaratna Walter P WP Lockett Trevor J TJ Gibbs Peter P Tonkin Andrew M AM Nelson Mark R MR Reid Christopher M CM Woods Robyn L RL Murray Anne M AM Winship Ingrid I McNeil John J JJ Schadt Eric E
Genetics in medicine : official journal of the American College of Medical Genetics 20200701 11
<h4>Purpose</h4>To measure the prevalence of medically actionable pathogenic variants (PVs) among a population of healthy elderly individuals.<h4>Methods</h4>We used targeted sequencing to detect pathogenic or likely pathogenic variants in 55 genes associated with autosomal dominant medically actionable conditions, among a population of 13,131 individuals aged 70 or older (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Participants had no previous di ...[more]