Biology subjects

Eley, T. C.

Publications and source records attributed to Eley, T. C..

8 recordsLinked to original sources

bioRxiv2026

The heritability of reinforcement learning parameters and their association with anxiety

Impaired learning that both novel and previously dangerous stimuli are safe (safety and extinction learning, respectively) are long standing, robust, and heritable features of anxiety disorders, representing potential endophenotypes. The computational mechanisms underpinning them have demonstrated associations with anxiety severity in recent studies. We undertook a pre-registered replication in a tenfold larger independent sample of twins (n = 925). Extinction learning rates were associated with anxiety severity ({rho}replication = -0.14, BFr0 = 1189. 67) but safety learning rates were not. Conversely, although safety learning rates showed modest heritability (h2safety = 0.16), extinction learning rates were not heritable. Accordingly, we were unable to identify genetic overlap between anxiety and either learning rate. Although this suggests neither learning rate is an anxiety endophenotype, we confirmed a cognitive-behavioral mechanism underpinning a robust marker of anxiety severity. Furthermore, we demonstrated heritability of a computationally modelled learning parameter, a key step towards establishing its biological basis.

genetics↗

bioRxiv2025

Computational modelling reveals slower safety learning and threat extinction are associated with higher anxiety severity in remote fear conditioning

Anxiety disorders are are chronic, pervasive, and debilitating; characterised by a persistent or exaggerated response to distal or abstract threats. Impaired threat discrimination (distinguishing safe from threatening stimuli) and impaired threat extinction (learning a once threatening stimulus is now safe), are known risk factors in the development and persistence of anxiety disorders. These effects can be experimentally elicited through fear conditioning. First, repeated trials of paired aversive and neutral stimuli are delivered during a fear acquisition phase, followed by repeated trials with no aversive stimuli in a fear extinction phase. The effects are typically measured through comparison of end-phase data points, or simple descriptive or statistical models. Computational modelling, by contrast, can offer a hypothesis-driven, trial-by-trial mechanistic account of fear conditioning. This unmasks within subject task variance by estimating the rate of threat learning, safety learning, and threat extinction, examining individual differences in the cognitive mechanisms behind anxiety. A normative sample (n = 145) underwent a differential fear conditioning task on a bespoke smartphone app, in addition to completing an anxiety severity measure (GAD-7). Computational models fitted to task data estimated learning rates. Whilst the threat learning rate showed no association, the threat extinction and safety learning rates showed small negative associations with anxiety severity (r = -0.218, p = 0.008 & r = -0.214, p = 0.01 respectively). These findings are in keeping with prior studies using traditional analytical approaches, and indicate that anxious individuals are not quicker to develop fear of a stimulus, but take more time than their non-anxious counterparts to learn that a stimulus is safe. This study strengthens the evidence for impairments in fear extinction in those with anxiety, and the importance of learning rates as an index of anxiety severity, a previously hidden cognitive mechanism underlying anxiety persistence.

neuroscience↗

bioRxiv2021

The winding roads to adulthood: a twin study

In the 21st century, emerging adulthood has stretched from the late teens through the twenties. Although this extended transition to adulthood can create stress, it can also offer opportunities to explore vocations and relationships that provide a better fit to individuals proclivities, including their genetic propensities. Here we report the results of the first systematic investigation of genetic and environmental influences on 57 psychological traits covering major issues in emerging adulthood such as aspirations, thoughts and attitudes, relationships and personality. We also investigate how these traits relate to physical and mental health, educational attainment and wellbeing using a sample of nearly 5000 pairs of UK twins aged 21-25 from the Twins Early Development Study. All 57 traits showed significant genetic influence, with an average heritability of 34% (SNP heritability [~]10%). Most of the variance (59% on average) was explained by non-shared environmental influences. These diverse traits were associated with mental health (average correlation .20), wellbeing (.16), physical health (.12) and educational attainment (.06). Shared genetic factors explained the majority of these correlations ([~]50%). Together, these emerging adulthood traits explained on average 30% of the variance in the outcomes (range = 8 to 69%), suggesting that these traits relate to the outcomes additively. We conclude that the environmental uncertainties of emerging adulthood in the 21st century do not diminish the importance of genetics. As adolescents travel down long and winding roads to adulthood, their trip is substantially influenced by genetic proclivities that nudge them down different paths leading to different destinations.

genetics↗

bioRxiv2021

Pathfinder: A gamified measure to integrate general cognitive ability into the biological, medical and behavioural sciences

Genome-wide association (GWA) studies have uncovered DNA variants associated with individual differences in general cognitive ability (g), but these are far from capturing heritability estimates obtained from twin studies. A major barrier to finding more of this missing heritability is assessment - the use of diverse measures across GWA studies as well as time and cost of assessment. In a series of four studies, we created a 15-minute (40-item), online, gamified measure of g that is highly reliable (alpha = .78; two-week test-retest reliability = .88), psychometrically valid and scalable; we called this new measure Pathfinder. In a fifth study, we administered this measure to 4,751 young adults from the Twins Early Development Study. This novel g measure, which also yields reliable verbal and nonverbal scores, correlated substantially with standard measures of g collected at previous ages (r ranging from .42 at age 7 to .57 at age 16). Pathfinder showed substantial twin heritability (.57, 95% CIs = .43, .68) and SNP heritability (.37, 95% CIs = .04, .70). A polygenic score computed from GWA studies of five cognitive and educational traits accounted for 12% of the variation in g, the strongest DNA-based prediction of g to date. Widespread use of this engaging new measure will advance research not only in genomics but throughout the biological, medical, and behavioural sciences.

genetics↗

bioRxiv2020

Evidence for distinct genetic and environmental influences on fear acquisition and extinction

BackgroundAnxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. Methods1937 twins aged 22-25 years, including 538 complete pairs from the Twins Early Development Study (TEDS) took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. ResultsTwin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15%, 30% and 15% respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations .4-.5). ConclusionsFear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.

genetics↗

bioRxiv2019

Comparison of adopted and non-adopted individuals reveals gene-environment interplay for education in the UK Biobank

Individual-level polygenic scores can now explain [~]10% of the variation in number of years of completed education. However, associations between polygenic scores and education capture not only genetic propensity but information about the environment that individuals are exposed to. This is because individuals passively inherit effects of parental genotypes, since their parents typically also provide the rearing environment. In other words, the strong correlation between offspring and parent genotypes results in an association between the offspring genotypes and the rearing environment. This is termed passive gene-environment correlation. We present an approach to test for the extent of passive gene-environment correlation for education without requiring intergenerational data. Specifically, we use information from 6311 individuals in the UK Biobank who were adopted in childhood to compare genetic influence on education between adoptees and non-adopted individuals. Adoptees rearing environments are less correlated with their genotypes, because they do not share genes with their adoptive parents. We find that polygenic scores are twice as predictive of years of education in non-adopted individuals compared to adoptees (R2= 0.074 vs 0.037, difference test p= 8.23 x 10-24). We provide another kind of evidence for the influence of parental behaviour on offspring education: individuals in the lowest decile of education polygenic score attain significantly more education if they are adopted, possibly due to educationally supportive adoptive environments. Overall, these results suggest that genetic influences on education are mediated via the home environment. As such, polygenic prediction of educational attainment represents gene-environment correlations just as much as it represents direct genetic effects.

genomics↗

bioRxiv2018

Genome-wide gene-environment analyses of depression and reported lifetime traumatic experiences in UK Biobank

Depression is more frequently observed among individuals exposed to traumatic events. The relationship between trauma exposure and depression, including the role of genetic variation, is complex and poorly understood. The UK Biobank concurrently assessed depression and reported trauma exposure in 126,522 genotyped individuals of European ancestry. We compared the shared aetiology of depression and a range of phenotypes, contrasting individuals reporting trauma exposure with those who did not (final sample size range: 24,094-92,957). Depression was heritable in participants reporting trauma exposure and in unexposed individuals, and the genetic correlation between the groups was substantial and not significantly different from 1. Genetic correlations between depression and psychiatric traits were strong regardless of reported trauma exposure, whereas genetic correlations between depression and body mass index (and related phenotypes) were observed only in trauma exposed individuals. The narrower range of genetic correlations in trauma unexposed depression and the lack of correlation with BMI echoes earlier ideas of endogenous depression.

genomics↗

bioRxiv2017

The Common Genetic Architecture of Anxiety Disorders

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n = 83 565) and an additional Current Anxiety Symptoms (n= 77 125) analysis. The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

genetics↗