Biology subjects

Howe, L. D.

Publications and source records attributed to Howe, L. D..

3 recordsLinked to original sources

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↗

bioRxiv2017

Assessing the causal role of body mass index on cardiovascular health in young adults: Mendelian randomization and recall-by-genotype analyses

BackgroundMendelian randomization (MR) studies of body mass index (BMI) and cardiovascular health in mid-to-late life suggest causal relationships, but the nature of these has not been explored systematically at younger ages. Using complementary MR and recall-by-genotype (RbG) methodologies, our objective was to estimate the causal effect of BMI on detailed measures of cardiovascular health in a population of young healthy adults.\n\nMethods and FindingsData from the Avon Longitudinal Study of Parents and Children were used. For MR analyses, a genetic risk score (GRS) comprising 97 independent single nucleotide polymorphisms (SNPs) and constructed using external weighting was used as an instrument to test the causal effect of each unit increase in BMI (kg/m2) on selected cardiovascular phenotypes measured at age 17 (N=7909). An independent enriched sample from the same cohort participated in a RbG study at age 21, which enabled more detailed cardiovascular phenotyping (N=418; 191/227 from the lower/upper [~]30% of a genome-wide GRS distribution predicting variation in BMI). The causal effect of BMI on the additional cardiovascular phenotypes was assessed by comparing the two recalled groups. Difference in mean BMI between RbG groups was 3.85kg/m2 (95% CI: 2.53, 4.63; P=6.09x1011). In both MR and RbG analyses, results indicated that higher BMI causes higher blood pressure (BP) and left ventricular mass (indexed to height2.7, LVMI) in young adults (e.g. difference in LVMI per kg/m2 using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87x10-06 and per 3.58kg/m2 using RbG: 1.65g/m2.7 95% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results indicated a causal role of higher BMI on higher stroke volume (SV; difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35; P=0.001) and cardiac output (CO; difference per 3.58kg/m2: 0.11l /min/m1.83; 95% CI: 0.03, 0.19; P=0.01). Neither analysis supported a causal role of higher BMI on heart rate.\n\nConclusionsComplementary MR and RbG causal methodologies, together with a range of appropriate sensitivity analyses, showed that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. These consistent results support efforts to prevent or reverse obesity in the young.

epidemiology↗