Whole-Exome Sequencing of an Exceptional Longevity Cohort.
J Gerontol A Biol Sci Med Sci
; 74(9): 1386-1390, 2019 08 16.
Article
en En
| MEDLINE
| ID: mdl-29750252
ABSTRACT
Centenarians represent a unique cohort to study the genetic basis for longevity and factors determining the risk of neurodegenerative disorders, including Alzheimer's disease (AD). The estimated genetic contribution to longevity is highest in centenarians and super-cententenarians, but few genetic variants have been shown to clearly impact this phenotype. While the genetic risk for AD and other dementias is now well understood, the frequency of known dementia risk variants in centenarians is not fully characterized. To address these questions, we performed whole-exome sequencing on 100 individuals of 98-108 years age in search of genes with large effect sizes towards the exceptional aging phenotype. Overall, we were unable to identify a rare protein-altering variant or individual genes with an increased burden of rare variants associated with exceptional longevity. Gene burden analysis revealed three genes of nominal statistical significance associated with extreme aging, including LYST, MDN1, and RBMXL1. Several genes with variants conferring an increased risk for AD and other dementias were identified, including TREM2, EPHA1, ABCA7, PLD3, MAPT, and NOTCH3. Larger centenarian studies will be required to further elucidate the genetic basis for longevity, and factors conferring protection against age-dependent neurodegenerative syndromes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Secuenciación del Exoma
/
Longevidad
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Asunto de la revista:
GERIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá