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.<br>Preprint available https://doi.org/10.1101/19007559<br>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. <br><br>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) &gt;0.1%, Hardy-Weinberg p-value &gt;1x10-9, and imputation quality &gt;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. <br><br>If used please cite paper Atkins et al. 2019 "A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Healthy Aging"<br>Fields are as follows:<br> SNP: dbSNP name of genetic marker, if available<br> CHR: chromosome<br> BP: base-pair position on CHR (hg19 / b37)<br> ALLELE1: effect allele<br> ALLELE0: non-effect allele<br> A1FREQ: frequency of ALLELE1INFO: Imputation quality<br>BETA: effect size from BOLT-LMM approximation to infinitesimal mixed model with respect to ALLELE1<br> SE: standard error of effect size<br> P_BOLT_LMM: non-infinitesimal mixed model association test p-value