Genetic basis of falling risk susceptibility in the UK Biobank Study

Katerina Trajanoska, Lotta J. Seppala, Carolina Medina-Gomez, Yi Hsiang Hsu, Sirui Zhou, Natasja M. van Schoor, Lisette C.P.G.M. de Groot, David Karasik, J. Brent Richards, Douglas P. Kiel, Andre G. Uitterlinden, John R.B. Perry, Nathalie van der Velde, Felix R. Day, Fernando Rivadeneira

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Article number543
JournalCommunications Biology
Issue number1
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
This research has been conducted using the UK Biobank Resource (Application number 24268). The Rotterdam Study was supported by The Netherlands Organization for Health Research and Development (ZonMw), The Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare, and Sport. In addition, the Netherlands Organization for Health Research and Development supported authors of this manuscript (ZonMw VIDI 016.136.367 to K.T., F.R., and C.M.G.).

Publisher Copyright:
© 2020, The Author(s).


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