Publications by authors named "Andrea G Allegrini"

10 Publications

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Using DNA to predict behaviour problems from preschool to adulthood.

J Child Psychol Psychiatry 2021 Sep 6. Epub 2021 Sep 6.

Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Background: One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems.

Method: Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems, and peer problems as rated by parents, teachers, and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalising, and internalising) across ages (from age 2 to 21) and across raters in penalised regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures.

Results: Multi-GPS prediction of behaviour problems increased from <2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability, although to a lesser extent, mirrored patterns of multi-GPS prediction as they increased from <40% to 83%.

Conclusions: The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our approach can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater, or GPS.
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http://dx.doi.org/10.1111/jcpp.13519DOI Listing
September 2021

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Genetic Correlates of Psychological Responses to the COVID-19 Crisis in Young Adult Twins in Great Britain.

Behav Genet 2021 03 24;51(2):110-124. Epub 2021 Feb 24.

Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK.

We investigated how the COVID-19 crisis and the extraordinary experience of lockdown affected young adults in England and Wales psychologically. One month after lockdown commenced (T2), we assessed 30 psychological and behavioural traits in more than 4000 twins in their mid-twenties and compared their responses to the same traits assessed in 2018 (T1). Mean changes from T1 to T2 were modest and inconsistent. Contrary to the hypothesis that major environmental changes related to COVID-19 would result in increased variance in psychological and behavioural traits, we found that the magnitude of individual differences did not change from T1 to T2. Twin analyses revealed that while genetic factors accounted for about half of the reliable variance at T1 and T2, they only accounted for ~ 15% of individual differences in change from T1 to T2, and that nonshared environmental factors played a major role in psychological and behavioural changes. Shared environmental influences had negligible impact on T1, T2 or T2 change. Genetic factors correlated on average .86 between T1 and T2 and accounted for over half of the phenotypic stability, as would be expected for a 2-year interval even without the major disruption of lockdown. We conclude that the first month of lockdown has not resulted in major psychological or attitudinal shifts in young adults, nor in major changes in the genetic and environmental origins of these traits. Genetic influences on the modest psychological and behavioural changes are likely to be the result of gene-environment correlation not interaction.
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http://dx.doi.org/10.1007/s10519-021-10050-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902241PMC
March 2021

Overview of CAPICE-Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe-an EU Marie Skłodowska-Curie International Training Network.

Eur Child Adolesc Psychiatry 2021 Jan 20. Epub 2021 Jan 20.

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
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http://dx.doi.org/10.1007/s00787-020-01713-2DOI Listing
January 2021

Multivariable G-E interplay in the prediction of educational achievement.

PLoS Genet 2020 11 17;16(11):e1009153. Epub 2020 Nov 17.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Polygenic scores are increasingly powerful predictors of educational achievement. It is unclear, however, how sets of polygenic scores, which partly capture environmental effects, perform jointly with sets of environmental measures, which are themselves heritable, in prediction models of educational achievement. Here, for the first time, we systematically investigate gene-environment correlation (rGE) and interaction (GxE) in the joint analysis of multiple genome-wide polygenic scores (GPS) and multiple environmental measures as they predict tested educational achievement (EA). We predict EA in a representative sample of 7,026 16-year-olds, with 20 GPS for psychiatric, cognitive and anthropometric traits, and 13 environments (including life events, home environment, and SES) measured earlier in life. Environmental and GPS predictors were modelled, separately and jointly, in penalized regression models with out-of-sample comparisons of prediction accuracy, considering the implications that their interplay had on model performance. Jointly modelling multiple GPS and environmental factors significantly improved prediction of EA, with cognitive-related GPS adding unique independent information beyond SES, home environment and life events. We found evidence for rGE underlying variation in EA (rGE = .38; 95% CIs = .30, .45). We estimated that 40% (95% CIs = 31%, 50%) of the polygenic scores effects on EA were mediated by environmental effects, and in turn that 18% (95% CIs = 12%, 25%) of environmental effects were accounted for by the polygenic model, indicating genetic confounding. Lastly, we did not find evidence that GxE effects significantly contributed to multivariable prediction. Our multivariable polygenic and environmental prediction model suggests widespread rGE and unsystematic GxE contributions to EA in adolescence.
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http://dx.doi.org/10.1371/journal.pgen.1009153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721131PMC
November 2020

Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis.

JAMA Psychiatry 2020 07;77(7):715-728

University of Bristol School of Psychological Science, Bristol, United Kingdom.

Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.

Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.

Design, Setting, And Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.

Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).

Main Outcomes And Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.

Results: The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008).

Conclusions And Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.0527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160753PMC
July 2020

Cognitive ability and education: How behavioural genetic research has advanced our knowledge and understanding of their association.

Neurosci Biobehav Rev 2020 04 20;111:229-245. Epub 2020 Jan 20.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

Cognitive ability and educational success predict positive outcomes across the lifespan, from higher earnings to better health and longevity. The shared positive outcomes associated with cognitive ability and education are emblematic of the strong interconnections between them. Part of the observed associations between cognitive ability and education, as well as their links with wealth, morbidity and mortality, are rooted in genetic variation. The current review evaluates the contribution of decades of behavioural genetic research to our knowledge and understanding of the biological and environmental basis of the association between cognitive ability and education. The evidence reviewed points to a strong genetic basis in their association, observed from middle childhood to old age, which is amplified by environmental experiences. In addition, the strong stability and heritability of educational success are not driven entirely by cognitive ability. This highlights the contribution of other educationally relevant noncognitive characteristics. Considering both cognitive and noncognitive skills as well as their biological and environmental underpinnings will be fundamental in moving towards a comprehensive, evidence-based model of education.
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http://dx.doi.org/10.1016/j.neubiorev.2020.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048133PMC
April 2020

The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence.

J Child Psychol Psychiatry 2020 01 20;61(1):30-39. Epub 2019 Sep 20.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: 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 childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence.

Methods: The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p.

Results: Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%).

Conclusions: Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems.
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http://dx.doi.org/10.1111/jcpp.13113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906245PMC
January 2020

Genetic Vulnerability for Smoking and Cannabis Use: Associations With E-Cigarette and Water Pipe Use.

Nicotine Tob Res 2019 05;21(6):723-730

Department of Developmental Psychopathology, Behavioural Science Institute, Faculty of Social Sciences, Radboud University, Nijmegen, The Netherlands.

Introduction: Cigarette smoking and cannabis use are heritable traits and share, at least in part, a common genetic substrate. In recent years, the prevalence of alternative methods of nicotine intakes, such as electronic cigarette (e-cigarette) and water pipe use, has risen substantially. We tested whether the genetic vulnerability underlying cigarettes smoking and cannabis use explained variability in e-cigarette and water pipe use phenotypes, as these vaping methods are alternatives for smoking tobacco cigarettes and joints.

Methods: On the basis of the summary statistics of the International Cannabis Consortium and the Tobacco and Genetics Consortium, we generated polygenic risk scores (PRSs) for smoking and cannabis use traits, and used these to predict e-cigarette and water pipe use phenotypes in a sample of 5025 individuals from the Netherlands Twin Register.

Results: PRSs for cigarettes per day were positively associated with lifetime e-cigarette use and early initiation of water pipe use, but only in ex-smokers (odds ratio = 1.43, R2 = 1.56%, p = .011) and never cigarette smokers (odds ratio = 1.35, R2 = 1.60%, p = .013) respectively.

Conclusions: Most associations of PRSs for cigarette smoking and cannabis use with e-cigarette and water pipe use were not significant, potentially due to a lack of power. The significant associations between genetic liability to smoking heaviness with e-cigarette and water pipe phenotypes are in line with studies indicating a common genetic background for substance-use phenotypes. These associations emerged only in nonsmokers, and future studies should investigate the nature of this observation.

Implications: Our study showed that genetic vulnerability to smoking heaviness is associated with lifetime e-cigarette use and age at initiation of water pipe use. This finding has implications for the current debate on whether alternative smoking methods, such as usage of vaping devices, predispose to smoking initiation and related behaviors.
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http://dx.doi.org/10.1093/ntr/nty150DOI Listing
May 2019

Gene × Environment contributions to autonomic stress reactivity in youth.

Dev Psychopathol 2019 02 17;31(1):293-307. Epub 2017 Dec 17.

Vrije Universiteit Amsterdam.

Dysregulated physiological stress reactivity has been suggested to impact the development of children and adolescents with important health consequences throughout the life span. Both environmental adversity and genetic predispositions can lead to physiological imbalances in stress systems, which in turn lead to developmental differences. We investigated genetic and environmental contributions to autonomic nervous system reactivity to a psychosocial stressor. Furthermore, we tested whether these effects were consistent with the differential susceptibility framework. Composite measures of adverse life events combined with socioeconomic status were constructed. Effects of these adversity scores in interaction with a polygenic score summarizing six genetic variants, which were hypothesized to work as susceptibility factors, were tested on autonomic nervous system measures as indexed by heart rate and heart rate variability. Results showed that carriers of more genetic variants and exposed to high adversity manifested enhanced heart rate variability reactivity to a psychosocial stressor compared to carriers of fewer genetic variants. Conversely, the stress procedure elicited a more moderate response in these individuals compared to carriers of fewer variants when adversity was low.
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http://dx.doi.org/10.1017/S095457941700181XDOI Listing
February 2019
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