A genome‐wide association study of the frailty index highlights brain pathways in ageing

Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial a...

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Bibliographic Details
Published in:Aging cell 2021-09, Vol.20 (9), p.e13459-n/a
Main Authors: Atkins, Janice L., Jylhävä, Juulia, Pedersen, Nancy L., Magnusson, Patrik K., Lu, Yi, Wang, Yunzhang, Hägg, Sara, Melzer, David, Williams, Dylan M., Pilling, Luke C.
Format: Article
Language:English
Subjects:
Adult
Aged
ageing
Aging
Aging - genetics
Aging - metabolism
Analysis
Asthma
Biobanks
Body mass index
Brain
Brain - metabolism
Cardiovascular diseases
Cortex (frontal)
DNA methylation
Frailty
Frailty - genetics
Frailty - metabolism
frailty index
Gene expression
Genetic aspects
Genetic factors
genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Geriatrics
Heritability
Histocompatibility antigen HLA
Humans
Medicin och hälsovetenskap
Meta-analysis
Middle Aged
Neurosis
Original Paper
Original Papers
Physiology
Public health
Risk factors
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Twins
Twins - genetics
UK Biobank
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Summary:Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome‐wide association study (GWAS) meta‐analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self‐reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p 
ISSN:1474-9718
1474-9726
1474-9726
DOI:10.1111/acel.13459