Validation of a polygenic risk score for frailty in the Lothian Birth Cohort 1936 and English longitudinal study of ageing

J P Flint; M Welstead; S R Cox; T C Russ; A Marshall; M Luciano

doi:10.1038/s41598-024-63229-y

Validation of a polygenic risk score for frailty in the Lothian Birth Cohort 1936 and English longitudinal study of ageing

Sci Rep. 2024 Jun 1;14(1):12586. doi: 10.1038/s41598-024-63229-y.

Authors

J P Flint^{1

2

3

4}, M Welstead^{5

6}, S R Cox^{7

5}, T C Russ^{6

8}, A Marshall^{9

10}, M Luciano^{7

5}

Affiliations

¹ Advanced Care Research Centre, School of Engineering, College of Science and Engineering, The University of Edinburgh, Edinburgh, UK. [email protected].
² Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK. [email protected].
³ Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK. [email protected].
⁴ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK. [email protected].
⁵ Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK.
⁶ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁷ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁸ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
⁹ Advanced Care Research Centre, School of Engineering, College of Science and Engineering, The University of Edinburgh, Edinburgh, UK.
¹⁰ School of Social and Political Science, University of Edinburgh, Edinburgh, UK.

Abstract

Frailty is a complex trait. Twin studies and high-powered Genome Wide Association Studies conducted in the UK Biobank have demonstrated a strong genetic basis of frailty. The present study utilized summary statistics from a Genome Wide Association Study on the Frailty Index 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, measured via the FI, at all-time points in LBC1936 and ELSA, explaining 2.1% (β = 0.15, 95%CI, 0.085-0.21) and 1.8% (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.

Publication types

Validation Study

MeSH terms

Aged
Aged, 80 and over
Aging* / genetics
Birth Cohort
England / epidemiology
Female
Frailty* / genetics
Genetic Risk Score
Genome-Wide Association Study*
Humans
Longitudinal Studies
Male
Multifactorial Inheritance*

Abstract

Publication types

MeSH terms

Grants and funding