ORCID Profile
0000-0001-5139-065X
Current Organisation
Royal Holloway University of London
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Publisher: Proceedings of the National Academy of Sciences
Date: 23-08-2022
Abstract: The use of spoken and written language is a fundamental human capacity. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in s les of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.
Publisher: Springer Science and Business Media LLC
Date: 09-04-2018
DOI: 10.1038/S41562-018-0332-5
Abstract: The etiology of in idual differences in educational attainment and occupational status includes genetic as well as environmental factors1-5 and can change as societies change3,6,7. The extent of genetic influence on these social outcomes can be viewed as an index of success in achieving meritocratic values of equality of opportunity by rewarding talent and hard work, which are to a large extent influenced by genetic factors, rather than rewarding environmentally driven privilege. To the extent that the end of the Soviet Union and the independence of Estonia led to an increase in meritocratic selection of in iduals in education and occupation, genetic influence should be higher in the post-Soviet era than in the Soviet era. Here we confirmed this hypothesis: DNA differences (single-nucleotide polymorphisms, SNPs) explained twice as much variance in educational attainment and occupational status in the post-Soviet era compared to the Soviet era in both polygenic score analyses and SNP heritability analyses of 12 500 Estonians. This is the first demonstration of a change in the extent of genetic influence in the same population following a massive and abrupt social change - in this case, the shift from a communist to a capitalist society.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2021
DOI: 10.1038/S41398-021-01480-X
Abstract: 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 s le 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 overall ) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG overall . 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 s le of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations ( r g ) among rater-specific assessment of AGG ranged from r g = 0.46 between self- and teacher-assessment to r g = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s 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 $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation ( r g = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 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.
Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2019
DOI: 10.1101/854927
Abstract: 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 s le 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 overall ) was 3.31% (SE=0.0038). We found no genome-wide significant SNPs for AGG overall . 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 s le of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations ( r g ) among rater-specific assessment of AGG ranged from r g =0.46 between self- and teacher-assessment to r g =0.81 between mother- and teacher-assessment. We obtained moderate to strong r g ’s 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 | r g | : 0.19 – 1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation ( r g =~ −0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range | r g | : 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.
Publisher: Proceedings of the National Academy of Sciences
Date: 06-10-2014
Abstract: Differences among children in educational achievement are highly heritable from the early school years until the end of compulsory education at age 16, when UK students are assessed nationwide with standard achievement tests [General Certificate of Secondary Education (GCSE)]. Genetic research has shown that intelligence makes a major contribution to the heritability of educational achievement. However, we show that other broad domains of behavior such as personality and psychopathology also account for genetic influence on GCSE scores beyond that predicted by intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE scores. These results underline the importance of genetics in educational achievement and its correlates. The results also support the trend in education toward personalized learning.
Publisher: Elsevier BV
Date: 2014
Publisher: Cold Spring Harbor Laboratory
Date: 06-2022
DOI: 10.1101/2022.06.01.494306
Abstract: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors, although mechanisms are not well understood. Here, we performed a meta-genome-wide association study within the EAGLE consortium and investigated polygenic overlap with later-life traits, including Attention-Deficit/Hyperactivity Disorder (ADHD) and cognition. We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months) and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated Single-Nucleotide Polymorphism heritability (SNP-h 2 ), genetic correlations (r g ) and modelled underlying genetic factor structures with multivariate models. Contributions of common genetic variation to early-life vocabulary were modest (SNP-h 2 : 0.08(SE=0.01) to 0.24(SE=0.03)) and multi-factorial. Genetic overlap between infant expressive and toddler receptive vocabulary was near zero (r g =0.07(SE=0.10)), although both measures were genetically related to toddler expressive vocabulary (r g =0.69(SE=0.14) and r g =0.67(SE=0.16), respectively). Consistently, polygenic association patterns with later-life traits differed: Genetic links with cognition emerged only in toddlerhood (e.g. toddler receptive vocabulary and intelligence: r g =0.36(SE=0.12)), despite comparable study power for infant measures. Furthermore, increased polygenic ADHD risk was associated with larger infant expressive vocabulary (r g =0.23(SE=0.08)), as confirmed by ADHD-symptom-based follow-up analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC-r g =0.54(SE=0.26)). Genetic relationships with toddler receptive vocabulary were, however, opposite (ALSPAC-r g =-0.74(SE=0.23)), highlighting developmental changes in genetic architectures. Multiple genetic components contribute to early-life vocabulary development, shaping polygenic association patterns with later-life ADHD symptoms and cognition.
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2020
DOI: 10.1101/2020.06.04.20121061
Abstract: Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium. The SNP heritability of total psychiatric problems was 5.4% (SE=0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2 , a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total psychiatric problem score were shared with known genetic variants for common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (r G 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (r G 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation of with intelligence, educational attainment, wellbeing, smoking, and body fat (r G 0.29).The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between psychiatric disorders and related traits.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAAC.2021.11.035
Abstract: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for s le overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INT Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood s les will be key in paving the way to future GWAS success.
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2021
DOI: 10.1101/2021.11.04.466897
Abstract: The use of spoken and written language is a capacity that is unique to humans. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, we present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, with total s le sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10 −8 ) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.
Publisher: American Medical Association (AMA)
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 25-10-2022
DOI: 10.1038/S41380-022-01793-3
Abstract: Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery s les (N = 85,359) and five independent replication s les (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10
Publisher: Public Library of Science (PLoS)
Date: 11-12-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kaili Rimfeld.