Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.
Nat Aging
; 2(1): 19-30, 2022 01.
Article
en En
| MEDLINE
| ID: mdl-37118362
ABSTRACT
Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits-healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health-in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near HTT and MAML3 using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estudio de Asociación del Genoma Completo
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Análisis de la Aleatorización Mendeliana
Tipo de estudio:
Clinical_trials
Aspecto:
Patient_preference
Límite:
Female
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Humans
Idioma:
En
Revista:
Nat Aging
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA