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Genetic basis of falling risk susceptibility in the UK Biobank Study.

Published version
Peer-reviewed

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Article

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Authors

Trajanoska, Katerina  ORCID logo  https://orcid.org/0000-0002-3792-4296
Seppala, Lotta J 
Medina-Gomez, Carolina  ORCID logo  https://orcid.org/0000-0001-7999-5538
Hsu, Yi-Hsiang 
Zhou, Sirui 

Abstract

Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual's fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a small, but significant SNP-based heritability (2.7%) and identified three novel fall-associated loci (Pcombined ≤ 5 × 10-8). Polygenic risk scores in two independent settings showed patterns of polygenic inheritance. Risk of falling had positive genetic correlations with fractures, identifying for the first time a pathway independent of bone mineral density. There were also positive genetic correlations with insomnia, neuroticism, depressive symptoms, and different medications. Negative genetic correlations were identified with muscle strength, intelligence and subjective well-being. Brain, and in particular cerebellum tissue, showed the highest gene expression enrichment for fall-associated variants. Overall, despite the highly heterogenic nature underlying fall risk, a proportion of the susceptibility can be attributed to genetics.

Description

Keywords

Accidental Falls, Adult, Aged, Biological Specimen Banks, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, United Kingdom

Journal Title

Commun Biol

Conference Name

Journal ISSN

2399-3642
2399-3642

Volume Title

3

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/2)
MRC (MC_UU_00006/2)