TY  - JOUR
IS  - 9
EP  - 13
A1  - Atkins, Janice L
A1  - Jylhava, Juulia
A1  - Pedersen, Nancy L
A1  - Magnusson, Patrik K
A1  - Lu, Yi
A1  - Wang, Yunzhang
A1  - Hagg, Sara
A1  - Melzer, David
A1  - Williams, Dylan M
A1  - Pilling, Luke C
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Cell Biology
KW  -  Geriatrics & Gerontology
KW  -  ageing
KW  -  frailty
KW  -  frailty index
KW  -  genetics
KW  -  UK Biobank
KW  -  SWEDISH TWIN REGISTRY
KW  -  BIOBANK
KW  -  VARIANTS
KW  -  INSTRUMENTS
KW  -  SARCOPENIA
KW  -  RESOURCE
KW  -  GENES
VL  - 20
TI  - A genome-wide association study of the frailty index highlights brain pathways in ageing
Y1  - 2021/09//
AV  - public
SN  - 1474-9718
N2  - 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.
PB  - WILEY
JF  - Aging Cell
N1  - © 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.
ID  - discovery10159329
UR  - https://doi.org/10.1111/acel.13459
ER  -