Validation of a polygenic risk score for Frailty in the Lothian Birth Cohort and English Longitudinal Study of Ageing
Validation of a polygenic risk score for Frailty in the Lothian Birth Cohort and English Longitudinal Study of Ageing
Abstract Frailty is a complex trait. Twin studies and a high-powered Genome Wide Association Study (GWAS) conducted in the UK Biobank have demonstrated a strong genetic basis of frailty. The present study utilized summary statistics from this GWAS to create and test the predictive power of frailty polygenic risk scores (PRS) in two independent samples – the Lothian Birth Cohort 1936 (LBC1936) and the English Longitudinal Study of Ageing (ELSA) aged 67-84 years. Multiple regression models were built to test the predictive power of frailty PRS at five time points. Frailty PRS significantly predicted frailty at all-time points in LBC1936 and ELSA, explaining 2.1% (β = 0.15, 95%CI, 0.085-0.21) and 1.6% (β = 0.14, 95%CI, 0.10-0.17) of the variance, respectively, at age ～68/～70 years (p < 0.001). This work demonstrates that frailty PRS can predict frailty in two independent cohorts, particularly at early ages (～68/～70). PRS have the potential to be valuable instruments for identifying those at risk for frailty and could be important for controlling for genetic confounders in epidemiological studies.
Luciano M、Flint J P、Cox S R、Russ T C、Welstead M、Marshall A
Lothian Birth Cohorts, Department of Psychology, University of Edinburgh||Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of EdinburghAdvanced Care Research Centre School of Engineering, College of Medicine and Veterinary Medicine, The University of Edinburgh||Lothian Birth Cohorts, Department of Psychology, University of Edinburgh||Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh||Alzheimer Scotland Dementia Research Centre, University of EdinburghLothian Birth Cohorts, Department of Psychology, University of Edinburgh||Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of EdinburghAlzheimer Scotland Dementia Research Centre, University of Edinburgh||Division of Psychiatry, Centre for Clinical Brain Sciences, University of EdinburghDepartment of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh||Alzheimer Scotland Dementia Research Centre, University of EdinburghAdvanced Care Research Centre School of Engineering, College of Medicine and Veterinary Medicine, The University of Edinburgh||School of Social and Political Science, University of Edinburgh
医药卫生理论医学研究方法基础医学
Luciano M,Flint J P,Cox S R,Russ T C,Welstead M,Marshall A.Validation of a polygenic risk score for Frailty in the Lothian Birth Cohort and English Longitudinal Study of Ageing[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2023.04.03.23288064.点此复制
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