Medically actionable pathogenic variants in a population of 13,131 healthy elderly individuals.
genetic testing
healthy elderly
medical actionability
pathogenic variants
penetrance
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
02
2020
accepted:
15
06
2020
revised:
14
06
2020
pubmed:
2
7
2020
medline:
29
4
2021
entrez:
2
7
2020
Statut:
ppublish
Résumé
To measure the prevalence of medically actionable pathogenic variants (PVs) among a population of healthy elderly individuals. 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. 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. 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.
Identifiants
pubmed: 32606442
doi: 10.1038/s41436-020-0881-7
pii: S1098-3600(21)00773-5
pmc: PMC7606791
mid: NIHMS1615430
doi:
Substances chimiques
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1883-1886Subventions
Organisme : NIA NIH HHS
ID : P30 AG024824
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG029824
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062682
Pays : United States
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