TY  - JOUR
PY  - 2020//
TI  - Genetic basis of falling risk susceptibility in the UK Biobank Study
JO  - Communications biology
A1  - Trajanoska, Katerina
A1  - Seppala, Lotta J.
A1  - Medina-Gomez, Carolina
A1  - Hsu, Yi-Hsiang
A1  - Zhou, Sirui
A1  - van Schoor, Natasja M.
A1  - de Groot, Lisette C. P. G. M.
A1  - Karasik, David
A1  - Richards, J. Brent
A1  - Kiel, Douglas P.
A1  - Uitterlinden, Andre G.
A1  - Perry, John R. B.
A1  - van der Velde, Nathalie
A1  - Day, Felix R.
A1  - Rivadeneira, Fernando
SP  - e543
EP  - e543
VL  - 3
IS  - 1
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 2399-3642
UR  - http://dx.doi.org/10.1038/s42003-020-01256-x
ID  - ref1
ER  -