Genome-wide summary statistics from the GWAS analysis of the Frailty
Index in participants of European descent aged 60+ from UK Biobank and TwinGene.
If used please cite paper Atkins et al. 2021 "A Genome-Wide Association Study of the Frailty Index Highlights Brain Pathways in Healthy Aging"
Included are two files: 1. meta-analysis results, 2. individual SNP associations in UK Biobank and TwinGene
README file included with each summary stats file. All base pair coordinates are GRCh37
Abstract
Frailty is a common geriatric syndrome,
strongly associated with disability, mortality and hospitalisation.
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,
aged 60-70 years) and Swedish TwinGene participants (n=10,616, aged
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<5*10-8). Many FI-associated loci have established associations
with traits such as body mass index, cardiovascular disease, smoking,
HLA proteins, depression and neuroticism; however, one appears to be
novel. The estimated single nucleotide polymorphism (SNP) heritability
of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes
expressed in the frontal cortex and hippocampus were significantly
downregulated (adjusted p<0.05). We also used Mendelian randomization
to identify modifiable traits and exposures that may affect frailty
risk, with a higher educational attainment genetic risk score being
associated with a lower degree of frailty. Risk of frailty is influenced
by many genetic factors, including well-known disease risk factors and
mental health, with particular emphasis on pathways in the brain.
Preprint available https://doi.org/10.1101/19007559