Dataset Information

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

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.

SUBMITTER: Trajanoska K

PROVIDER: S-EPMC7527955 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Trajanoska Katerina K Seppala Lotta J LJ Medina-Gomez Carolina C Hsu Yi-Hsiang YH Zhou Sirui S van Schoor Natasja M NM de Groot Lisette C P G M LCPGM Karasik David D Richards J Brent JB Kiel Douglas P DP Uitterlinden Andre G AG Perry John R B JRB van der Velde Nathalie N Day Felix R FR Rivadeneira Fernando F

Communications biology 20200930 1

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 (P<sub>combined</sub> ≤ 5 × 10<sup>-8</sup>). Polygenic risk scores in two independent settings show ...[more]

PMID: 32999390

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Project description:Background & aimsPeople with a higher genetic risk for obesity are more likely to develop cardiovascular disease (CVD), and healthy plant-based dietary patterns may be associated with decreased risks of obesity and cardiovascular events. We investigated whether adherence to healthy plant-foods-rich dietary patterns might attenuate risks of obesity and related cardiovascular abnormalities for people at genetically higher risk of obesity.MethodsThis study included 121,799 middle-aged adults in UK Biobank who were initially free of metabolic diseases and cancer. We calculated a healthful plant-based diet index (hPDI) based on 17 major food groups as well as a genetic risk score (GRS) for obesity consisting of body mass index (BMI)-associated variants. The incidence of cardiovascular events (myocardial infarction, MI, or stroke) was prospectively followed during a mean (SD) 5.1 (0.9) years.ResultsWe found significant interactions between GRS and hPDI on adiposity (Pinteraction <0.0001); adherence to hPDI was more strongly associated with lower levels of adiposity among participants with higher GRS than those with lower GRS. Further, we found a similar pattern of GRS-hPDI interactions on untreated hypertension (Pinteraction = 0.0036). When we tested GRS-hPDI interactions on cardiovascular events, adherence to hPDI was more strongly associated with a decreased risk of MI among people with high GRS (above median) than those with low GRS (Pinteraction = 0.006). Among participants with high GRS, high adherence to hPDI (the top tertile of hPDI) was associated with an HR 0.54 (95% CI: 0.39, 0.74) for MI, as compared to low adherence.ConclusionsAdherence to healthy plant-based dietary patterns significantly attenuated risks of cardiovascular abnormalities for people at genetically higher risk of obesity. Our results support the precision medicine strategies considering genetics and dietary habits to modify cardiovascular health for people at higher risk of genetically determined obesity.

Project description:Background and objectivesThe association between patterns of physical/mental activity and dementia and how it is affected by disease susceptibility remains unknown. We aimed to examine the association between patterns of physical and mental activity and dementia and whether it can be modified by disease susceptibility to dementia.MethodsIn a prospective cohort study based on UK Biobank, 501,376 dementia-free participants were recruited in 2006-2010 and followed from 1 year after the recruitment date until the end of 2019 for ascertainment of dementia. Data on physical (i.e., physical activity at leisure time, housework-related activity, and transportation) and mental (i.e., intelligence, social contact, and use of electronic device) activity were collected using questionnaires at recruitment. Cox models were used to estimate the associations of physical and mental activity-related items, as well as major activity patterns identified by principal component analysis, with the risk of dementia, adjusted for multiple confounders. The modification role of disease susceptibility on such associations was assessed through stratified analyses by the polygenic risk score (PRS) of dementia generated based on summary statistics of independent genome-wide association studies, by the APOE genotype, and by the self-reported family history of dementia.ResultsThe mean age at recruitment was 56.53, and 45.60% of the participants were male. During a mean follow-up of 10.66 years, 5,185 dementia cases were identified. When analyzed separately, multiple studied items related to physical and mental activity showed significant associations with the risk of dementia. The pattern analyses revealed that a higher level of adherence to activity patterns related to frequent vigorous and other exercises (hazard ratio 0.65, 95% CI 0.59-0.71), housework-related activity (0.79, 0.72-0.85), and friend/family visit (0.85, 0.75-0.96) was associated with a lower risk of dementia. We obtained comparable results for vascular dementia and Alzheimer disease as well as in the stratified analyses by the PRS for dementia, APOE genotype, or family history of dementia.DiscussionActivity patterns more adherent to frequent vigorous and other exercises, housework-related activity, and friend/family visit were associated with a reduced risk of multiple types of dementia. Such associations are independent of disease susceptibility, highlighting the potential of these physical and mental activity patterns, as effective interventions, in the primary prevention of dementia.

Dataset Information

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

Publications

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

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