scholarly journals The Genetic Architecture of Alzheimer’s Disease Risk: A Genomic Structural Equation Modelling Study

2021 ◽  
Author(s):  
Isabelle F Foote ◽  
Benjamin M Jacobs ◽  
Georgina Mathlin ◽  
Cameron J Watson ◽  
Phazha LK Bothongo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Equation Modelling ◽  
Structural Equation ◽  
Genetic Architecture ◽  
Disease Risk ◽  
Modifiable Risk Factors ◽  
Equation Modelling ◽  
Shared Genetic

AbstractBackgroundTargeting modifiable risk factors may have a role in the prevention of Alzheimer’s disease. However, the mechanisms by which these risk factors influence Alzheimer’s risk remain incompletely understood. Genomic structural equation modelling can reveal patterns of shared genetic architecture that provide insight into the pathophysiology of complex traits.MethodsWe identified genome-wide association studies for Alzheimer’s disease and its major modifiable risk factors: less education, hearing loss, hypertension, high alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, type 2 diabetes, sleep disturbance and socioeconomic deprivation. We performed linkage disequilibrium score regression among these traits, followed by exploratory factor analysis, confirmatory factor analysis and structural equation modelling.ResultsWe identified complex networks of linkage disequilibrium among Alzheimer’s disease risk factors. The data were best explained by a bi-factor model, incorporating a Common Factor for Alzheimer’s risk, and three orthogonal sub-clusters of risk factors, which were validated across the two halves of the autosome. The first sub-cluster was characterised by risk factors related to sedentary lifestyle behaviours, the second by traits associated with reduced life expectancy and the third by traits that are possible prodromes of Alzheimer’s disease. Alzheimer’s disease was more genetically distinct and displayed minimal shared genetic architecture with its risk factors, which was robust to the exclusion of APOE.ConclusionShared genetic architecture may contribute to epidemiological associations between Alzheimer’s disease and its risk factors. Understanding the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.

scholarly journals Exploring the shared genetic architecture of modifiable risk factors and related endophenotypes of Alzheimer’s disease: A genomic SEM study

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Isabelle F. Foote ◽  
Benjamin M. Jacobs ◽  
Alastair J. Noyce ◽  
Ania Korszun ◽  
Kamaldeep S. Bhui ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Architecture ◽  
Modifiable Risk Factors ◽  
Sem Study ◽  
Shared Genetic

scholarly journals Relative impact of red blood cell transfusion and anaemia on 5-year mortality in cardiac surgery

2020 ◽  
Author(s):  
Long Tran ◽  
Guri Greiff ◽  
Alexander Wahba ◽  
Hilde Pleym ◽  
Vibeke Videm
Keyword(s):  
Risk Factors ◽  
Cardiac Surgery ◽  
Blood Cell ◽  
Structural Equation Modelling ◽  
Structural Equation ◽  
Open Heart ◽  
Patient Risk ◽  
Equation Modelling ◽  
Rbc Transfusion ◽  
Preoperative Anaemia

Abstract Graphical Abstract OBJECTIVES The aim was to compare the relative effects of red blood cell (RBC) transfusion and preoperative anaemia on 5-year mortality following open-heart cardiac surgery using structural equation modelling. We hypothesized that patient risk factors associated with RBC transfusion are of larger importance than transfusion itself. METHODS This prospective cohort study, part of the Cardiac Surgery Outcome Study at St. Olavs University Hospital, Trondheim, Norway, included open-heart on-pump cardiac surgery patients operated on from 2000 through 2017 (n = 9315). Structural equation modelling, which allows for intervariable correlations, was used to analyse pathway diagrams between known risk factors and observed mortality between 30 days and 5 years postoperatively. Observation times between 30 days and 1 year, and 1–5 years postoperatively were also compared with the main analysis. RESULTS In a simplified model, preoperative anaemia had a larger effect on 5-year mortality than RBC transfusion (standardized coefficients: 0.17 vs 0.09). The complete model including multiple risk factors showed that patient risk factors such as age (0.15), anaemia (0.10), pulmonary disease (0.11) and higher creatinine level (0.12) had larger effects than transfusion (0.03). Results from several sensitivity analyses supported the main findings. The models showed good fit. CONCLUSIONS Preoperative anaemia had a larger impact on 5-year mortality than RBC transfusion. Differences in 5-year mortality were mainly associated with patient risk factors.

scholarly journals Potentially Modifiable Risk Factors in the Development of Alzheimer’s Disease

US Neurology ◽  
2010 ◽  
Vol 05 (02) ◽  
pp. 18 ◽  
Author(s):  
Simon Forstmeier ◽  
Andreas Maercker ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Emotional Health ◽  
Social Activity ◽  
Empirical Support ◽  
Epidemiological Studies ◽  
Vascular Risk Factors ◽  
Modifiable Risk Factors ◽  
Vascular Risk

This article summarises empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD), drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors and nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention. First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces the risk of AD. Second, the absence of vascular risk factors such as diabetes, hypertension, hypercholesterol and obesity reduces the risk of AD. More prevention trials are warranted to investigate the preventative effects of an active and stimulating lifestyle on the one hand, and vascular health on the other, in delaying the onset of AD or slowing its progression.

Sign in / Sign up

Export Citation Format

Share Document