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Medically actionable pathogenic variants in a population of 13,131 healthy elderly individuals


Lacaze, P and Sebra, R and Riaz, M and Tiller, J and Revote, J and Phung, J and Parker, EJ and Orchard, SG and Lockery, JE and Wolfe, R and Strahl, M and Wang, YC and Chen, R and Sisco, D and Arnold, T and Thompson, BA and Buchanan, DD and Macrae, FA and James, PA and Abhayaratna, WP and Lockett, TJ and Gibbs, P and Tonkin, AM and Nelson, MR and Reid, CM and Woods, RL and Murray, AM and Winship, I and McNeil, JJ and Schadt, E, Medically actionable pathogenic variants in a population of 13,131 healthy elderly individuals, Genetics in Medicine, 22, (11) pp. 1883-1886. ISSN 1098-3600 (2020) [Refereed Article]

Copyright Statement

Copyright 2020 American College of Medical Genetics and Genomics

DOI: doi:10.1038/s41436-020-0881-7


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.

Item Details

Item Type:Refereed Article
Keywords:genetic testing, healthy elderly, medical actionability, pathogenic variants, penetrance
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Medical genetics (excl. cancer genetics)
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Health related to ageing
UTAS Author:Nelson, MR (Professor Mark Nelson)
ID Code:141825
Year Published:2020
Web of Science® Times Cited:13
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-11-24
Last Modified:2020-12-09

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