Genome-Wide Association Study of the Frailty Index - Atkins et al. 2019

Genome-wide summary statistics from the GWAS analysis of the Frailty Index in UK Biobank participants of European descent aged 60 to 70 years. Preprint available https://doi.org/10.1101/19007559 We used a Frailty Index (FI) based on the accumulation of deficits model (Searle et al. 2008), as validated in UK Biobank previously for its ability to predict all-cause mortality (Williams et al. 2018). The FI was derived using 49 self-reported baseline data variables in UK Biobank. Variables were based on a variety of physiological and mental health domains, and included symptoms, disabilities and diagnosed diseases, which were self-reported by participants at baseline. The FI was generated using a complete-case sample with information on all 49 individual components and presented as a proportion of the sum of all deficits. The FI was quantile normalised (i.e. transformed into a normal distribution) prior to the genome-wide association study (due to the skew of the untransformed trait). The analysis included 164,610 participants of European descent aged 60 to 70 with complete Frailty Index data. Results are from UK Biobank genetic data release version 3 (including imputation from HRC and the combined UK10K and 1000 Genomes panels) including 16.4million genetic variants that met the following criteria: minor allele frequency (MAF) >0.1%, Hardy-Weinberg p-value >1x10-9, and imputation quality >0.3. We used the BOLT-LMM (v2.3.2) software used for the GWAS itself (Loh et al. 2015), which uses linear mixed-effects modelling to account for genetic relatedness and confounding by ancestry. Models included age, sex, assessment centre (22 categories), and genotyping array (two categories: Axiom or BiLEVE) as covariates. If used please cite paper Atkins et al. 2019 "A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Healthy Aging" Fields are as follows: SNP: dbSNP name of genetic marker, if available CHR: chromosome BP: base-pair position on CHR (hg19 / b37) ALLELE1: effect allele ALLELE0: non-effect allele A1FREQ: frequency of ALLELE1INFO: Imputation quality BETA: effect size from BOLT-LMM approximation to infinitesimal mixed model with respect to ALLELE1 SE: standard error of effect size P_BOLT_LMM: non-infinitesimal mixed model association test p-value