Frailty

Summary data for the frailty index were retrieved from the most recent GWAS meta‐analysis of the UK Biobank and TwinGene, including 175 226 individuals of European ancestry. ⁶ The frailty index is a commonly used definition for frailty that is based on the accumulation of age‐related deficits. ¹⁴ According to this phenotype, frailty is measured on a continuous score between 0 and 1, calculated by summing up the number of health deficits and dividing it by the total number of deficits measured (at least 30), covering signs, symptoms, disabilities and diseases. ¹⁴

Summary data for the frailty phenotype were obtained from a large‐scale GWAS with 386 565 participants of European ancestry enrolled in the UK Biobank. ⁷ The frailty phenotype is another dominant frailty assessment instrument, consisting of five criteria (weight loss, exhaustion, low physical activity, slow walking speed and weak grip strength). ¹⁵ In the original GWAS, the frailty phenotype was analysed as an ordinal score ranging from 0 to 5 to reduce information loss and improve statistical power, rather than as a usually modelled binary variable with ≥3 criteria defined as frailty.

It is worth noting that there is a lack of consensus regarding the definition of frailty, with ongoing debates about the conceptual framework to be measured. Despite this, the frailty index and the frailty phenotype are two most known operational definitions of frailty that have been validated as good predictors of many adverse outcomes in large‐scale cohorts. Although the frailty index and the frailty phenotype have distinct conceptual underpinnings, they share commonalities in terms of determinants and identification of frailty.