Biology subjects

Fawns-Ritchie, C.

Publications and source records attributed to Fawns-Ritchie, C..

6 recordsLinked to original sources

bioRxiv2019

Genetic contributions to health literacy

Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5,783 English Longitudinal Study of Ageing (ELSA) participants (mean age=65.49, SD=9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004-2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE=7.2%). Greater odds of having adequate health literacy were associated with a 1SD higher polygenic score for general cognitive ability (OR=1.34, 95% CI 1.26-1.42), verbal-numerical reasoning (OR=1.30, 1.23-1.39), and years of schooling (OR=1.29, 1.21-1.36). Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health (OR=0.92, 0.87-0.98) and schizophrenia (OR=0.91, 0.85-0.96). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic aetiology. Larger studies are required to obtain accurate estimates of SNP-based heritability, and to discover specific health literacy-associated genetic variants.

epidemiology↗

bioRxiv2019

Brain imaging correlates of general intelligence in UK Biobank

The associations between indices of brain structure and measured intelligence are not clear. In part, this is because the evidence to date comes from mostly small and heterogenous studies. Here, we report brain structure-intelligence associations on a large sample from the UK Biobank study. The overall N = 29,004, with N = 18,363 participants providing both brain MRI and cognitive data, and a minimum N = 7318 providing the MRI data alongside a complete four-test battery. Participants age range was 44-81 years (M = 63.13, SD = 7.48). A general factor of intelligence (g) was extracted from four varied cognitive tests, accounting for one third of the variance in the cognitive test scores. The association between (age-and sex-corrected) total brain volume and a latent factor of general intelligence is r = 0.275, 95% C.I. = [0.252, 0.299]. A model that incorporated multiple global measures of grey and white matter macro-and microstructure accounted for more than double the g variance in older participants compared to those in middle-age (13.4% and 5.9%, respectively). There were no sex differences in the magnitude of associations between g and total brain volume or other global aspects of brain structure. The largest brain regional correlates of g were volumes of the insula, frontal, anterior/superior and medial temporal, posterior and paracingulate, lateral occipital cortices, thalamic volume, and the white matter microstructure of thalamic and association fibres, and of the forceps minor.

neuroscience↗

bioRxiv2019

Associations between vascular risk factors and brain MRI indices in UK Biobank

AimsSeveral factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macro- and microstructure in large community-dwelling populations across middle- and older age.\n\nMethods and ResultsAssociations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholersterolaemia, BMI, and waist-hip ratio) and both global and regional brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-77 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 [≤] 1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.\n\nConclusionHigher levels of VRFs were associated with poorer brain health across grey and white matter macro- and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasise the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

neuroscience↗

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

Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

General cognitive function is a prominent human trait associated with many important life outcomes1,2, including longevity3. The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants4,5,6. Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360; age range = 16 to 102). We found 9,714 genome-wide significant SNPs (P<5 x 10-8) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ, ATXN1, MAPT, AUTS2, and P2RY6. Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function; many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent samples. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.

genetics↗

bioRxiv2017

116 independent genetic variants influence the neuroticism personality trait in over 329,000 UK Biobank individuals.

Neuroticism is a stable personality trait 1; twin studies report heritability between 30% and 50% 2, and SNP-based heritability is about 15% 3. Higher levels of neuroticism are associated with poorer mental and physical health 4,5, and the economic burden of neuroticism for societies is high 6. To date, genome-wide association (GWA) studies of neuroticism have identified up to 11 genetic loci 3,7. Here we report 116 significant independent genetic loci from a GWA of neuroticism in 329,821 UK Biobank participants, with replication available in a GWA meta-analysis of neuroticism in 122,867 individuals. Genetic signals for neuroticism were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (rg = .82, SE=.03), major depressive disorder (rg = .69, SE=.07) and subjective wellbeing (rg = -.68, SE=.03) alongside other mental health traits. These discoveries significantly advance our understanding of neuroticism and its association with major depressive disorder.

genetics↗