eprintid: 10159329
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/15/93/29
datestamp: 2022-11-16 10:39:15
lastmod: 2022-11-16 10:39:15
status_changed: 2022-11-16 10:39:15
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Atkins, Janice L
creators_name: Jylhava, Juulia
creators_name: Pedersen, Nancy L
creators_name: Magnusson, Patrik K
creators_name: Lu, Yi
creators_name: Wang, Yunzhang
creators_name: Hagg, Sara
creators_name: Melzer, David
creators_name: Williams, Dylan M
creators_name: Pilling, Luke C
title: A genome-wide association study of the frailty index highlights brain pathways in ageing
ispublished: pub
divisions: UCL
divisions: B02
divisions: D14
divisions: GA3
divisions: G17
keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, Geriatrics & Gerontology, ageing, frailty, frailty index, genetics, UK Biobank, SWEDISH TWIN REGISTRY, BIOBANK, VARIANTS, INSTRUMENTS, SARCOPENIA, RESOURCE, GENES
note: © 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
abstract: Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) meta-analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self-reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10−8). Many FI-associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on pathways in the brain.
date: 2021-09
date_type: published
publisher: WILEY
official_url: https://doi.org/10.1111/acel.13459
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1884949
doi: 10.1111/acel.13459
medium: Print-Electronic
lyricists_name: Williams, Dylan
lyricists_id: DMWIL55
actors_name: Williams, Dylan
actors_id: DMWIL55
actors_role: owner
funding_acknowledgements: MR/M023095/1 [UK Medical Research Council]; 2015--03255 [Swedish Research Council]; 2018--02077 [Swedish Research Council]; U01-066134 [NIH DK]; [Swedish Foundation for Strategic Research (SSF)]; 20070481 [Heart and Lung foundation]; R01 AG04563 [NIH]; AG10175 [NIH]; AG028555 [NIH]; [MacArthur Foundation Research Network on Successful Aging]; 2009--0795 [Swedish Council for Working Life and Social Research (FAS/FORTE)]; [Strategic Research Program in Epidemiology at Karolinska Institutet]; [Loo & Hans Osterman Foundation]; [Foundation for Geriatric Diseases at Karolinska Institutet]
full_text_status: public
publication: Aging Cell
volume: 20
number: 9
article_number: e13459
pages: 13
event_location: England
issn: 1474-9718
citation:        Atkins, Janice L;    Jylhava, Juulia;    Pedersen, Nancy L;    Magnusson, Patrik K;    Lu, Yi;    Wang, Yunzhang;    Hagg, Sara;             ... Pilling, Luke C; + view all <#>        Atkins, Janice L;  Jylhava, Juulia;  Pedersen, Nancy L;  Magnusson, Patrik K;  Lu, Yi;  Wang, Yunzhang;  Hagg, Sara;  Melzer, David;  Williams, Dylan M;  Pilling, Luke C;   - view fewer <#>    (2021)    A genome-wide association study of the frailty index highlights brain pathways in ageing.                   Aging Cell , 20  (9)    , Article e13459.  10.1111/acel.13459 <https://doi.org/10.1111/acel.13459>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10159329/1/A%20genome-wide%20association%20study%20of%20the%20frailty%20index%20highlights%20brain%20pathways%20in%20ageing.pdf