A5027283866- Genetic Associations and Epidemiology
- Cognitive Abilities and Testing
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
- Nutrition, Genetics, and Disease
- Health, Environment, Cognitive Aging
- Child and Adolescent Psychosocial and Emotional Development
- Health Systems, Economic Evaluations, Quality of Life
- Lipoproteins and Cardiovascular Health
- RNA modifications and cancer
- Obesity, Physical Activity, Diet
- Epigenetics and DNA Methylation
- Genetic and phenotypic traits in livestock
- Cardiovascular Function and Risk Factors
- Spatial Cognition and Navigation
- Bioinformatics and Genomic Networks
- Health Promotion and Cardiovascular Prevention
- Personality Disorders and Psychopathology
- Diabetes, Cardiovascular Risks, and Lipoproteins
- BRCA gene mutations in cancer
- Child and Animal Learning Development
- Computational Drug Discovery Methods
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reading and Literacy Development
- Cancer-related molecular mechanisms research
Genomics (United Kingdom)
2020-2024
King's College London
2016-2023
Medical Research Council
2016-2017
Polygenic scores are a popular tool for prediction of complex traits. However, estimates in samples unrelated participants can include effects population stratification, assortative mating, and environmentally mediated parental genetic effects, form genotype-environment correlation (rGE). Comparing genome-wide polygenic score (GPS) predictions individuals with between siblings within-family design is powerful approach to identify these different sources prediction. Here, we compared within-...
Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between traits also supports p. This study systematically investigates manifestation this common across self-, parent- and teacher-rated measures adolescence.The sample included 7,026 twin pairs from Twins Early Development Study (TEDS). First, we employed multivariate models to estimate environmental influences...
Abstract We present and assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases 25 quantitative traits being made available on individuals in UKB. also release benchmarking software tool to enable like-for-like performance evaluation different same disease or trait. Extensive shows UKB Release outperform broad 81 published PRSs. For many we validate PRS algorithms other cohorts. The availability 53 allows systematic assessment their properties, increased...
The predictive utility of polygenic scores is increasing, and many scoring methods are available, but it unclear which method performs best. This study evaluates the within a reference-standardized framework, uses common set variants reference-based estimates linkage disequilibrium allele frequencies to construct scores. Eight score were tested: p-value thresholding clumping (pT+clump), SBLUP, lassosum, LDpred1, LDpred2, PRScs, DBSLMM SBayesR, evaluating their performance predict outcomes in...
There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely clinical practice manage preventative treatment.Using UK Biobank resource, we developed our own polygenic score for coronary artery (CAD). We an additional 60 000 individuals develop integrated tool (IRT) that combined with established tools (either American Heart Association/American College of Cardiology pooled cohort equations [PCE] or...
We assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits that has been made available on individuals in UKB, using unified pipeline PRS evaluation. also release benchmarking software tool to enable like-for-like performance evaluation different same disease or trait. Extensive shows UKB Release outperform broad 76 published PRSs. For many we validate algorithms separate cohort (100,000 Genomes Project). The availability 53...
Abstract A genome-wide polygenic score (GPS), derived from a 2013 association study ( N =127,000), explained 2% of the variance in total years education EduYears ). In follow-up =329,000), new GPS explains up to 4%. Here, we tested between this latest and educational achievement scores at ages 7, 12 16 an independent sample 5825 UK individuals. We found that greater amounts over time, 9% age 16, accounting for 15% heritable variance. This is strongest prediction date quantitative behavioral...
Abstract It has recently been proposed that a single dimension, called the p factor, can capture person’s liability to mental disorder. Relevant hypothesis, recent genetic research found surprisingly high correlations between pairs of psychiatric disorders. Here, for first time, we compare from different methods and examine their support factor. We tested hypothesis factor by applying principal component analysis matrices major disorders estimated three methods—family study, genome-wide...
Abstract The Twins Early Development Study (TEDS) is a longitudinal twin study that recruited over 16,000 twin-pairs born between 1994 and 1996 in England Wales through national birth records. More than 10,000 of these families are still engaged the study. TEDS was representative sample population Wales. Rich cognitive emotional/behavioral data have been collected from twins infancy to emerging adulthood, with collection at first contact ages 2, 3, 4, 7, 8, 9, 10, 12, 14, 16, 18 21, enabling...
The parental feeding practices (PFPs) of excessive restriction food intake ('restriction') and pressure to increase consumption ('pressure') have been argued causally influence child weight in opposite directions (high causing overweight; high underweight). However could also 'elicit' PFPs. A novel approach is investigate gene-environment correlation between genetic influences on BMI Genome-wide polygenic scores (GPS) combining BMI-associated variants were created for 10,346 children...
On average, students attending selective schools outperform their non-selective counterparts in national exams. These differences are often attributed to value added by the school, as well factors use select pupils, including ability, achievement and, cases where charge tuition fees or located affluent areas, socioeconomic status. However, possible role of DNA between different types has not yet been considered. We used a UK-representative sample 4814 genotyped investigate exam performance...
Associations between exposures and outcomes reported in epidemiological studies are typically unadjusted for genetic confounding. We propose a two-stage approach estimating the degree to which such observed associations can be explained by First, we assess attenuation of exposure effects regressions controlling increasingly powerful polygenic scores. Second, use structural equation models estimate confounding using heritability estimates derived from both SNP-based twin-based studies....
Abstract Individuals differ in their level of general anxiety as well towards specific activities, such mathematics and spatial tasks. Both anxieties correlate moderately with anxiety, but the aetiology association remains unexplored. Moreover, factor structure is to date unknown. The present study investigated its aetiology, origins a sample 1,464 19-21-year-old twin pairs from UK representative Twins Early Development Study. Participants reported general, part an online battery tests. We...
Abstract For most complex traits, DNA-based heritability (‘SNP heritability’) is roughly half that of twin-based heritability. A previous report from the Twins Early Development Study suggested this gap much greater for childhood behaviour problems than other domains. If true, finding important because SNP heritability, not twin ceiling genome-wide association studies. With twice sample size as report, we estimated heritabilities ( N up to 4653 unrelated individuals) and compared them with...
Genome-wide polygenic scores (GPS) can be used to predict individual genetic risk and resilience. For example, a GPS for years of education (EduYears) explains substantial variance in cognitive traits such as general ability educational achievement. Personality are also known contribute differences However, the association between EduYears personality remains largely unexplored. Here, we test relation EduYears, neuroticism, well-being, 6 motivation domains: Academic Motivation, Extraversion,...
Spatial abilities encompass several skills differentiable from general cognitive ability (g). Importantly, spatial have been shown to be significant predictors of many life outcomes, even after controlling for g. To date, no studies analyzed the genetic architecture diverse using a multivariate approach. We developed "gamified" measures putative abilities. The battery 10 tests was administered online 1,367 twin pairs (age 19-21) UK-representative Twins Early Development Study (TEDS). show...
Polygenic scores are increasingly powerful predictors of educational achievement. It is unclear, however, how sets polygenic scores, which partly capture environmental effects, perform jointly with measures, themselves heritable, in prediction models Here, for the first time, we systematically investigate gene-environment correlation (rGE) and interaction (GxE) joint analysis multiple genome-wide (GPS) measures as they predict tested achievement (EA). We EA a representative sample 7,026...
Abstract Background One goal of the DNA revolution is to predict problems in order prevent them. We tested here if prediction behaviour from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and raters using a multi-GPS approach that includes GPS for adult psychiatric disorders as well childhood problems. Method Our sample included 3,065 genotyped unrelated individuals Twins Early Development Study who were assessed longitudinally hyperactivity, conduct,...
It is now possible to create individual-specific genetic scores, called genome-wide polygenic scores (GPS). We used a GPS for years of education (EduYears) predict reading performance assessed at UK National Curriculum Key Stages 1 (age 7), 2 12) and 3 14) on tests administered ages 7 12 in sample 5,825 unrelated individuals. EduYears accounts up 5% the variance age 14. predictions remained significant after accounting general cognitive ability family socioeconomic status. Reading children...
Abstract Recent advances in genomics are producing powerful DNA predictors of complex traits, especially cognitive abilities. Here, we leveraged summary statistics from the most recent genome-wide association studies intelligence and educational attainment to build prediction models general ability achievement. To this end, compared performances multi-trait genomic polygenic scoring methods. In a representative UK sample 7,026 children at age 12 16, show that can now predict up 11 percent...