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GWAS Study

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

Trajanoska K, Seppala LJ, Medina-Gomez C et al.

32999390 PubMed ID
GWAS Study Type
459683 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

TK
Trajanoska K
SL
Seppala LJ
MC
Medina-Gomez C
HY
Hsu YH
ZS
Zhou S
VS
van Schoor NM
DG
de Groot LCPGM
KD
Karasik D
RJ
Richards JB
KD
Kiel DP
UA
Uitterlinden AG
PJ
Perry JRB
VD
van der Velde N
DF
Day FR
RF
Rivadeneira F
Chapter II

Abstract

Summary of the research findings

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.

89,076 European ancestry cases, 362,103 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

459683
Total Participants
GWAS
Study Type
Yes
Replicated
2,215 cases, 6289 controls
Replication Participants
European
Ancestry
U.K., Netherlands
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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