TY - JOUR
T1 - Genetic basis of falling risk susceptibility in the UK Biobank Study
AU - Trajanoska, Katerina
AU - Seppala, Lotta J.
AU - Medina-Gomez, Carolina
AU - Hsu, Yi Hsiang
AU - Zhou, Sirui
AU - van Schoor, Natasja M.
AU - de Groot, Lisette C.P.G.M.
AU - Karasik, David
AU - Richards, J.B.
AU - Kiel, Douglas P.
AU - Uitterlinden, Andre G.
AU - Perry, John R.B.
AU - van der Velde, Nathalie
AU - Day, Felix R.
AU - Rivadeneira, Fernando
PY - 2020/9/30
Y1 - 2020/9/30
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.
AB - 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.
U2 - 10.1038/s42003-020-01256-x
DO - 10.1038/s42003-020-01256-x
M3 - Article
AN - SCOPUS:85091719094
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
M1 - 543
ER -