Shared genetic influence on frailty and chronic widespread pain: a study from TwinsUK

Introduction: frailty is an increased vulnerability to adverse health outcomes, across multiple physiological systems, with both environmental and genetic drivers. The two most commonly used measures are Rockwood's frailty index (FI) and Fried's frailty phenotype (FP). Material and methods: the present study included 3626 individuals from the TwinsUK Adult Twin Registry. We used the classical twin model to determine whether FI and FP share the same latent aetiological factors. We also investigated the relationship between frailty and chronic widespread musculoskeletal pain (CWP), another holistic age-related condition with significant clinical impact. Results: FP and FI shared underlying genetic and environmental aetiology. CWP was associated with both frailty measures, and health deficits appeared to mediate the relationship between phenotypic frailty and pain. Latent genetic factors underpinning CWP were shared with frailty. While frailty was increased in the twins reporting pain, co-twin regression analysis indicated that the relationship between CWP and frailty is reduced after accounting for shared genetic and environmental factors. Conclusions: both measures of frailty tap the same root causes, thus this work helps unify frailty research. We confirmed a strong association between CWP and frailty, and showed a large and significant shared genetic aetiology of both phenomena. Our findings argue against pain being a significant causative factor in the development of frailty, favouring common causation. This study highlights the need to manage CWP in frail individuals and undertake a Comprehensive Geriatric Assessment in individuals presenting with CWP. Finally, the search for genetic factors underpinning CWP and frailty could be aided by integrating measures of pain and frailty.