EWAS meta-analysis of frailty in two European twin cohorts

EWAS summary statistics for the paper "Epigenome-wide analysis of frailty: results from two European twin cohorts" by Mak et al. (2024).Method: We first performed four cross-sectional EWASs of the frailty index (FI) in SATSA 450K, SATSA EPIC, LSADT 1997, and LSADT 2007 samples using generalized estimating equations where DNA methylation levels of CpG sites (i.e., normalized β values, representing proportion of methylation) were used as the dependent variables and FI as the independent variable. The models were adjusted for age, sex, smoking, and body mass index (BMI). Both twins from each pair were included in the models, and we accounted for twin relatedness using cluster-robust standard errors. The models in LSADT were additionally adjusted for batch and estimated cellular compositions (CD4 cells, CD8 cells, natural killer cells, monocytes, granulocytes, and B cells). We considered the FI both as a continuous variable (per 0.1 increase) and a 3-group categorical variable (frail vs. non-frail and prefrail vs. non-frail). Afterwards, a fixed-effect inverse variance weighted meta-analysis was performed using the metafor R package. The meta-analysis included 368,249 CpGs that were available in the 450K samples (i.e., SATSA 450K, LSADT 1997, and LSADT 2007). Potential heterogeneity was assessed using the I2 value. CpGs associated with either the continuous or categorical FI at a false discovery rate (FDR) <.05 were considered as statistically significant.List of EWAS datasets:"EWAS_FI_cont_summary_stat.txt": EWAS summary statistics of the continuous FI"EWAS_frail-vs-nonfrail_summary_stat.txt": EWAS summary statistics of the categorical FI (frail vs. non-frail)"EWAS_prefrail-vs-nonfrail_summary_stat.txt": EWAS summary statistics of the categorical FI (prefrail vs. non-frail)