Biology subjects

Hagenaars, S.

Publications and source records attributed to Hagenaars, S..

4 recordsLinked to original sources

bioRxiv2017

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

INTRODUCTIONIt is unclear whether polygenic risk for neurodegenerative disease is associated with cognitive performance and physical health.\n\nMETHODSThis study tested whether polygenic scores for Alzheimers disease (AD), Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) are associated with cognitive performance and physical health. Group-based analyses were performed to compare associations with cognitive and physical function outcomes in the top and bottom 10% for the three neurodegenerative polygenic risk scores.\n\nRESULTSHigher polygenic risk scores for AD, ALS, and FTD were associated with lower cognitive performance. Higher polygenic risk scores for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS.\n\nDISCUSSIONOur results suggest overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.

genetics↗

bioRxiv2017

Genome-wide association study of depression phenotypes in UK Biobank (n = 322,580) identifies the enrichment of variants in excitatory synaptic pathways

Depression is a polygenic trait that causes extensive periods of disability and increases the risk of suicide, a leading cause of death in young people. Previous genetic studies have identified a number of common risk variants which have increased in number in line with increasing sample sizes. We conducted a genome-wide association study (GWAS) in the largest single population-based cohort to date, UK Biobank. This allowed us to estimate the effects of {approx} 8 million genetic variants in 320,000 people for three depression phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. Each phenotype was found to be significantly genetically correlated with the results from a previous independent study of clinically defined MDD. We identified 14 independent loci that were significantly associated (P < 5 x 10-8) with broad depression, two independent variants for probable MDD, and one independent variant for ICD-coded MDD. Gene-based analysis of our GWAS results with MAGMA revealed 46 regions significantly associated (P < 2.77 x 10-6) with broad depression, two significant regions for probable MDD and one significant region for ICD-coded MDD. Gene region-based analysis of our GWAS results with MAGMA revealed 59 regions significantly associated (P < 6.02 x 10-6) with broad depression, of which 27 were also detected by gene-based analysis. Variants for broad depression were enriched in pathways for excitatory neurotransmission, mechanosensory behavior, postsynapse, neuron spine and dendrite. This study provides a number of novel genetic risk variants that can be leveraged to elucidate the mechanisms of MDD and low mood.

genetics↗

bioRxiv2017

Genetic contributions to trail making test performance in UK Biobank

The Trail Making Test is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the trail making test and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The SNP-based heritability estimates for trail-making measures were 7.9 % (part A), 22.4 % (part B), and 17.6 % (part B - part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg > 0.6), general cognitive function (rg > 0.6), processing speed (rg > 0.7), and memory (rg > 0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed, and memory (standardized {beta} between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.

genetics↗

bioRxiv2016

Cognitive ability and physical health: a Mendelian randomization study

Causes of the association between cognitive ability and health remain unknown, but may reflect a shared genetic aetiology. This study examines the causal genetic associations between cognitive ability and physical health. We carried out two-sample Mendelian randomization analyses using the inverse-variance weighted method to test for causality between later life cognitive ability, educational attainment (as a proxy for cognitive ability in youth), BMI, height, systolic blood pressure, coronary artery disease, and type 2 diabetes using data from six independent GWAS consortia and the UK Biobank sample (N = 112 151). BMI, systolic blood pressure, coronary artery disease and type 2 diabetes showed negative associations with cognitive ability; height was positively associated with cognitive ability. The analyses provided no evidence for casual associations from health to cognitive ability. In the other direction, higher educational attainment predicted lower BMI, systolic blood pressure, coronary artery disease, type 2 diabetes, and taller stature. The analyses indicated no causal association from educational attainment to physical health. The lack of evidence for causal associations between cognitive ability, educational attainment, and physical health could be explained by weak instrumental variables, poorly measured outcomes, or the small number of disease cases.

genetics↗