Biology subjects

Korologou-Linden, R.

Publications and source records attributed to Korologou-Linden, R..

5 recordsLinked to original sources

bioRxiv2020

Exploring the causal effects of genetic liability to ADHD and Autism on Alzheimer's disease

BackgroundThere are very few studies investigating possible links between Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and Alzheimers disease and these have been limited by small sample sizes, diagnostic and recall bias. However, neurocognitive deficits affecting educational attainment in individuals with ADHD could be risk factors for Alzheimers later in life while hyper plasticity of the brain in ASD and strong positive genetic correlations of ASD with IQ and educational attainment could be protective against Alzheimers. MethodsWe estimated the bidirectional total causal effects of genetic liability to ADHD and ASD on Alzheimers disease through two-sample Mendelian randomization. We investigated their direct effects, independent of educational attainment and IQ, through Multivariable Mendelian randomization. ResultsThere was limited evidence to suggest that genetic liability to ADHD (OR=1.00, 95% CI: 0.98 to 1.02, p=0.39) or ASD (OR=0.99, 95% CI: 0.97 to 1.01, p=0.70) was associated with risk of Alzheimers disease. Similar causal effect estimates were identified when the direct effects, independent of educational attainment (ADHD: OR=1.00, 95% CI: 0.99 to 1.01, p=0.07; ASD: OR=0.99, 95% CI: 0.98 to 1.00, p=0.28) and IQ (ADHD: OR=1.00, 95% CI: 0.99 to 1.02. p=0.29; ASD: OR=0.99, 95% CI: 0.98 to 1.01, p=0.99), were assessed. Finally, genetic liability to Alzheimers disease was not found to have a causal effect on risk of ADHD or ASD (ADHD: OR=1.12, 95% CI: 0.86 to 1.44, p=0.37; ASD: OR=1.19, 95% CI: 0.94 to 1.51, p=0.14). ConclusionsIn the first study to date investigating the causal associations between genetic liability to ADHD, ASD and Alzheimers, within an MR framework, we found limited evidence to suggest a causal effect. It is important to encourage future research using ADHD and ASD specific subtype data, as well as longitudinal data in order to further elucidate any associations between these conditions.

genetics↗

bioRxiv2019

Is disrupted sleep a risk factor for Alzheimers disease? Evidence from a two-sample Mendelian randomization analysis

INTRODUCTIONIt is established that Alzheimers disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD.\n\nMETHODSMendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness) on AD risk.\n\nRESULTSOverall, there was little evidence that sleep traits affect the risk of AD. There was some evidence to suggest that self-reported daytime napping was associated with lower AD risk (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.50 to 0.99). Some other sleep traits (accelerometer-measured eveningness and sleep duration, and self-reported daytime sleepiness) had ORs for AD risk of a similar magnitude to daytime napping, but were less precisely estimated.\n\nDISCUSSONOur findings provide tentative evidence that daytime napping may reduce AD risk. However, findings should be replicated using independent samples.

epidemiology↗

bioRxiv2019

Polygenic risk score for Alzheimer’s disease and trajectories of cardiometabolic risk factors in children

INTRODUCTIONCardiometabolic factors are implicated in the aetiology of Alzheimers disease and may lie on the pathways linking genetic variants to Alzheimers disease across the life course. We examined whether polygenic risk scores (PRS) were associated with cardiometabolic health indicators through childhood and adolescence.\n\nMETHODSIn 7,977 participants from the Avon Longitudinal Study of Parents and Children, we tested whether a PRS for Alzheimers disease was associated with trajectories of cardiometabolic risk factors. We examined trajectories for height 1-18 years; lean and fat mass 9-18 years; systolic and diastolic blood pressure 7-18 years; glucose and C-reactive protein 9-18 years; insulin 10-18 years; high and low-density lipoproteins and triglycerides birth-18 years. We also examined birthweight, interleukin-6 (IL-6) at age 9 years and physical activity at ages 11, 12, and 15 years.\n\nRESULTSNo consistent associations were observed between the PRS excluding genetic variants in the apolipoprotein E (ApoE) gene region and cardiometabolic factors trajectories across childhood and adolescence.\n\nCONCLUSIONWe did not detect evidence to suggest that the PRS for Alzheimers disease acts through childhood and adolescent cardiometabolic risk factors. Further studies should examine whether these associations emerge later in adulthood when variation in cardiometabolic risk factors is likely to be greater.

epidemiology↗

bioRxiv2018

Education, intelligence and Alzheimer’s disease: Evidence from a multivariable two-sample Mendelian randomization study

ObjectivesTo examine whether educational attainment and intelligence have causal effects on risk of Alzheimers disease (AD), independently of each other.\n\nDesignTwo-sample univariable and multivariable Mendelian Randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on risk of AD.\n\nParticipants17,008 AD cases and 37,154 controls from the International Genomics of Alzheimers Project (IGAP) consortium\n\nMain outcome measureOdds ratio of AD per standardised deviation increase in years of schooling and intelligence\n\nResultsThere was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23% to 49%) and 35% (95% CI: 25% to 43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account, but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis.\n\nConclusionsThere is robust evidence for an independent, causal effect of intelligence in lowering AD risk, potentially supporting a role for cognitive training interventions to improve aspects of intelligence. However, given the observed causal effect of educational attainment on intelligence, there may also be support for policies aimed at increasing length of schooling to lower incidence of AD.

genetics↗

bioRxiv2017

The causal effect of educational attainment on Alzheimer’s disease: A two-sample Mendelian randomization study

BackgroundObservational evidence suggests that higher educational attainment is protective for Alzheimers disease (AD). It is unclear whether this association is causal or confounded by demographic and socioeconomic characteristics. We examined the causal effect of educational attainment on AD in a two-sample MR framework.\n\nMethodsWe extracted all available effect estimates of the 74 single nucleotide polymorphisms (SNPs) associated with years of schooling from the largest genome-wide association study (GWAS) of educational attainment (N=293,723) and the GWAS of AD conducted by the International Genomics of Alzheimers Project (n=17,008 AD cases and 37,154 controls). SNP-exposure and SNP-outcome coefficients were combined using an inverse variance weighted approach, providing an estimate of the causal effect of each SD increase in years of schooling on AD. We also performed appropriate sensitivity analyses examining the robustness of causal effect estimates to the various assumptions and conducted simulation analyses to examine potential survival bias of MR analyses.\n\nFindingsWith each SD increase in years of schooling (3.51 years), the odds of AD were, on average, reduced by approximately one third (odds ratio= 0.63, 95% confidence interval [CI]: 0.48 to 0.83, p<0.001). Causal effect estimates were consistent when using causal methods with varying MR assumptions or different sets of SNPs for educational attainment, lending confidence to the magnitude and direction of effect in our main findings. There was also no evidence of survival bias in our study.\n\nInterpretationOur findings support a causal role of educational attainment on AD, whereby an additional [~]3.5 years of schooling reduces the odds of AD by approximately one third.

epidemiology↗