Genome-Wide Association Study of the Frailty Index - Atkins et al. 2021

Genome-wide summary statistics from the GWAS analysis of the Frailty Index in participants of European descent aged 60+ from UK Biobank and TwinGene.<br>If used please cite paper Atkins et al. 2021 "A Genome-Wide Association Study of the Frailty Index Highlights Brain Pathways in Healthy Aging"<br>Included are two files: 1. meta-analysis results, 2. individual SNP associations in UK Biobank and TwinGene<br><br>README file included with each summary stats file. All base pair coordinates are GRCh37<br>Abstract<br>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&lt;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&lt;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.<br>Preprint available https://doi.org/10.1101/19007559