Biology subjects

Anderson, E. L.

Publications and source records attributed to Anderson, E. L..

8 recordsLinked to original sources

bioRxiv2024

Deciphering the Influence of Socioeconomic Status on Brain Structure: Insights from Mendelian Randomization

Socioeconomic status (SES) influences physical and mental health, however its relation with brain structure is less well documented. Here, we examine the role of SES on brain structure using Mendelian randomisation. First, we conduct a multivariate genome-wide association study of SES using individual, household, and area-based measures of SES, with an effective sample size of n=893,604. We identify 469 loci associated with SES and distil these loci into those that are common across measures of SES and those specific to each indicator. Second, using an independent sample of [~]35,000 we provide evidence to suggest that total brain volume is a causal factor in higher SES, and that SES is protective against white matter hyperintensities as a proportion of intracranial volume (WMHicv). Third, we find evidence that whilst differences in cognitive ability explain some of the causal effect of SES on WMHicv, differences in SES still afford a protective effect against WMHicv, independent of that made by cognitive ability.

genetics↗

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↗

bioRxiv2020

Is genetic liability to ADHD and ASD causally linked to educational attainment?

BackgroundIndividuals with Attention Deficit Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD) are at risk of poor educational outcomes. Parental educational attainment has also been associated with risk of ADHD/ASD in the offspring. Despite evidence that ADHD and ASD show genetic links to educational attainment, less is known on the causal nature of the associations and the possible role of IQ. MethodsWe assessed the total causal effects of genetic liability to ADHD/ASD on educational attainment using two-sample Mendelian randomization (MR). We assessed the possible contribution of IQ to the identified causal effects by estimating the "direct" effects of ADHD/ASD on educational attainment, independent of IQ, using Multivariable MR (MVMR). Reverse direction analyses were performed. The latest GWAS meta-analyses of ADHD, ASD, educational attainment and IQ were used. Causal effect estimates were generated using inverse variance weighted models (IVW). Sensitivity analyses were performed to assess the robustness of the estimates and the presence of pleiotropy. ResultsGenetic liability to ADHD had a total (MRIVW:-3.3 months per doubling of liability to ADHD; 95%CI: -4.8 to -1.9; pval= 5*10-6) and direct negative causal effect on educational attainment (MVMRIVW:-1.6 months per doubling of liability to ADHD; 95%CI: -2.5 to -0.6; pval= 4*10-4). There was little evidence of a total causal effect of genetic liability to ASD on educational attainment (MRIVW: 4 days, per doubling of liability to ASD; 95%CI: -4.9 months to 5.6 months; pval= 0.9) but some evidence of a direct effect not via IQ (MVMRIVW:29 days per doubling the genetic liability to ASD; 95%CI: 2 to 48; pval= 0.03). Reverse direction analyses suggested that genetic liability to higher educational attainment was associated with lower risk of ADHD (MRIVWOR: 0.3 per standard deviation (SD) increase; 95%CI: 0.26 to 0.36; pval= 6*10-51), even after IQ was entered in the models (MVMRIVWOR: 0.33 per SD increase; 95%CI: 0.26 to 0.43; pval= 6*10-17). On the contrary, there was evidence consistent with a positive causal effect of genetic liability to higher educational attainment on risk of ASD (MRIVWOR: 1.51 per SD increase; 95%CI: 1.29 to 1.77; pval= 4*10-7), which was found to be largely explained by IQ (MVMRIVWOR per SD increase: 1.24; 95%CI: 0.96 to 1.60; pval= 0.09). ConclusionsOur findings suggest that despite the genetic and phenotypic overlap between ADHD and ASD, they present highly differentiated causal associations with educational attainment. This highlights the necessity for specialized educational interventions for children with ADHD and ASD. Further research is needed in order to decipher whether the identified causal effects reflect parentally transmitted effects, diagnostic masking, or selection bias.

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

Investigating causal relationships between sleep traits and risk of breast cancer: a Mendelian randomization study

ObjectiveTo examine whether sleep traits have a causal effect on risk of breast cancer.\n\nDesignMultivariable regression, one- and two-sample Mendelian randomization.\n\nSettingThe UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.\n\nParticipants156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.\n\nExposuresSelf-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.\n\nMain outcome measuresBreast cancer (prevalent and incident cases in UK Biobank, prevalent cases only in BCAC).\n\nResultsIn multivariable regression analysis using data on breast cancer incidence in UK Biobank, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93, 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated sleep duration and 57 SNPs associated with insomnia symptoms, one-sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (HR 0.85, 95% 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two-sample MR using data from BCAC supported findings for a protective effect of morning preference (OR 0.88, 95% CI 0.82, 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02, 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.\n\nConclusionsWe found consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of sleep duration on breast cancer risk.

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↗

bioRxiv2018

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association study (GWAS) meta-analyses of relative caloric intake from fat, protein, carbohydrates and sugar in over 235,000 individuals. We identified 21 approximately independent lead SNPs. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg {approx} 0.15 - 0.5). Relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood poverty (|rg| {approx} 0.1 - 0.3). Overall, our results show that the relative intake of each macronutrient has a distinct genetic architecture and pattern of genetic correlations suggestive of health implications beyond caloric content.

genetics↗