@article {459, title = {Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people}, journal = {Proceedings of the National Academy of Sciences (PNAS)}, volume = {119}, year = {2022}, pages = {e2202764119}, abstract = {

The use of spoken and written language is a fundamental human capacity. Individual 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 individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples 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.

}, keywords = {genome-wide association study, language, meta-analysis, reading}, doi = {10.1073/pnas.2202764119}, author = {Eising, Else and Mirza-Schreiber, Nazanin and de Zeeuw, Eveline L and Wang, Carol A and Truong, Dongnhu T and Allegrini, Andrea G and Shapland, Chin Yang and Zhu, Gu and Wigg, Karen G and Gerritse, Margot L and Molz, Barbara and Alag{\"o}z, G{\"o}kberk and Gialluisi, Alessandro and Abbondanza, Filippo and Rimfeld, Kaili and van Donkelaar, Marjolein and Liao, Zhijie and Jansen, Philip R and Andlauer, Till F M and Bates, Timothy C and Bernard, Manon and Blokland, Kirsten and Bonte, Milene and B{\o}rglum, Anders D and Bourgeron, Thomas and Brandeis, Daniel and Ceroni, Fabiola and Cs{\'e}pe, Val{\'e}ria and Dale, Philip S and de Jong, Peter F and DeFries, John C and D{\'e}monet, Jean-Fran\c cois and Demontis, Ditte and Feng, Yu and Gordon, Scott D and Guger, Sharon L and Hayiou-Thomas, Marianna E and Hern{\'a}ndez-Cabrera, Juan A and Hottenga, Jouke-Jan and Hulme, Charles and Kere, Juha and Kerr, Elizabeth N and Koomar, Tanner and Landerl, Karin and Leonard, Gabriel T and Lovett, Maureen W and Lyytinen, Heikki and Martin, Nicholas G and Martinelli, Angela and Maurer, Urs and Michaelson, Jacob J and Moll, Kristina and Monaco, Anthony P and Morgan, Angela T and N{\"o}then, Markus M and Pausova, Zdenka and Pennell, Craig E and Pennington, Bruce F and Price, Kaitlyn M and Rajagopal, Veera M and Ramus, Franck and Richer, Louis and Simpson, Nuala H and Smith, Shelley D and Snowling, Margaret J and Stein, John and Strug, Lisa J and Talcott, Joel B and Tiemeier, Henning and van der Schroeff, Marc P and Verhoef, Ellen and Watkins, Kate E and Wilkinson, Margaret and Wright, Margaret J and Barr, Cathy L and Boomsma, Dorret I and Carreiras, Manuel and Franken, Marie-Christine J and Gruen, Jeffrey R and Luciano, Michelle and M{\"u}ller-Myhsok, Bertram and Newbury, Dianne F and Olson, Richard K and Paracchini, Silvia and Paus, Tom{\'a}\v s and Plomin, Robert and Reilly, Sheena and Schulte-K{\"o}rne, Gerd and Tomblin, J Bruce and van Bergen, Elsje and Whitehouse, Andrew J O and Willcutt, Erik G and St Pourcain, Beate and Francks, Clyde and Fisher, Simon E} } @article {428, title = {Higher aggression is related to poorer academic performance in compulsory education}, journal = {Journal of Child Psychology and Psychiatry}, volume = {62}, year = {2021}, pages = {327{\textendash}338}, abstract = {

BACKGROUND: To conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education.

METHOD: We studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7-16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self-reports. Academic performance was measured with teacher-rated grade point averages (ages 12-14) or standardized test scores (ages 12-16). Random effect meta-analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self-ratings (in three cohorts).

RESULTS: All between-family analyses indicated significant negative aggression-academic performance associations with correlations ranging from -.06 to -.33. Results were similar across different ages, instruments and raters and either with teacher-rated grade point averages or standardized test scores as measures of academic performance. Meta-analytical r\&$\#$39;s were -.20 and -.23 for parental and self-ratings, respectively. In within-family analyses of all twin pairs, the negative aggression-academic performance associations were statistically significant in 14 out of 17 analyses (r = -.17 for parental- and r = -.16 for self-ratings). Separate analyses in monozygotic (r = -.07 for parental and self-ratings), same-sex dizygotic (r\&$\#$39;s = -.16 and -.17 for parental and self-ratings) and opposite-sex dizygotic (r\&$\#$39;s = -.21 and -.19 for parental and self-ratings) twin pairs suggested partial confounding by genetic effects.

CONCLUSIONS: There is a robust negative association between aggression and academic performance in compulsory education. Part of these associations were explained by shared genetic effects, but some evidence of a negative association between aggression and academic performance remained even in within-family analyses of monozygotic twin pairs.

}, keywords = {Aggression, cognition, development, educational attainment, school performance}, doi = {10.1111/jcpp.13273}, author = {Vuoksimaa, Eero and Rose, Richard J and Pulkkinen, Lea and Palviainen, Teemu and Rimfeld, Kaili and Lundstr{\"o}m, Sebastian and Bartels, Meike and van Beijsterveldt, Catharina and Hendriks, Anne and de Zeeuw, Eveline L and Plomin, Robert and Lichtenstein, Paul and Boomsma, Dorret I and Kaprio, Jaakko} } @article {449, title = {Higher aggression is related to poorer academic performance in compulsory education}, journal = {Journal of Child Psychology and Psychiatry}, volume = {62}, year = {2021}, pages = {327{\textendash}338}, abstract = {

BACKGROUND: To conduct a comprehensive assessment of the association between aggression and academic performance in compulsory education.

METHOD: We studied aggression and academic performance in over 27,000 individuals from four European twin cohorts participating in the ACTION consortium (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies). Individual level data on aggression at ages 7-16 were assessed by three instruments (Achenbach System of Empirically Based Assessment, Multidimensional Peer Nomination Inventory, Strengths and Difficulties Questionnaire) including parental, teacher and self-reports. Academic performance was measured with teacher-rated grade point averages (ages 12-14) or standardized test scores (ages 12-16). Random effect meta-analytical correlations with academic performance were estimated for parental ratings (in all four cohorts) and self-ratings (in three cohorts).

RESULTS: All between-family analyses indicated significant negative aggression-academic performance associations with correlations ranging from -.06 to -.33. Results were similar across different ages, instruments and raters and either with teacher-rated grade point averages or standardized test scores as measures of academic performance. Meta-analytical r\&$\#$39;s were -.20 and -.23 for parental and self-ratings, respectively. In within-family analyses of all twin pairs, the negative aggression-academic performance associations were statistically significant in 14 out of 17 analyses (r = -.17 for parental- and r = -.16 for self-ratings). Separate analyses in monozygotic (r = -.07 for parental and self-ratings), same-sex dizygotic (r\&$\#$39;s = -.16 and -.17 for parental and self-ratings) and opposite-sex dizygotic (r\&$\#$39;s = -.21 and -.19 for parental and self-ratings) twin pairs suggested partial confounding by genetic effects.

CONCLUSIONS: There is a robust negative association between aggression and academic performance in compulsory education. Part of these associations were explained by shared genetic effects, but some evidence of a negative association between aggression and academic performance remained even in within-family analyses of monozygotic twin pairs.

}, keywords = {Aggression, cognition, development, educational attainment, school performance}, doi = {10.1111/jcpp.13273}, author = {Vuoksimaa, Eero and Rose, Richard J and Pulkkinen, Lea and Palviainen, Teemu and Rimfeld, Kaili and Lundstr{\"o}m, Sebastian and Bartels, Meike and van Beijsterveldt, Catharina and Hendriks, Anne and de Zeeuw, Eveline L and Plomin, Robert and Lichtenstein, Paul and Boomsma, Dorret I and Kaprio, Jaakko} } @article {435, title = {Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction}, journal = {Nature Genetics}, volume = {53}, year = {2021}, pages = {35{\textendash}44}, abstract = {

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57\% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.

}, doi = {10.1038/s41588-020-00754-2}, author = {Demange, Perline A and Malanchini, Margherita and Mallard, Travis T and Biroli, Pietro and Cox, Simon R and Grotzinger, Andrew D and Tucker-Drob, Elliot M and Abdellaoui, Abdel and Arseneault, Louise and van Bergen, Elsje and Boomsma, Dorret I and Caspi, Avshalom and Corcoran, David L and Domingue, Benjamin W and Harris, Kathleen Mullan and Ip, Hill F and Mitchell, Colter and Moffitt, Terrie E and Poulton, Richie and Prinz, Joseph A and Sugden, Karen and Wertz, Jasmin and Williams, Benjamin S and de Zeeuw, Eveline L and Belsky, Daniel W and Harden, K Paige and Nivard, Michel G} } @article {450, title = {Teacher-rated aggression and co-occurring behaviors and emotional problems among schoolchildren in four population-based European cohorts}, journal = {PLoS One}, volume = {16}, year = {2021}, pages = {e0238667}, abstract = {

Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7-14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47-0.80) and lower with internalizing problems (r: 0.02-0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the higher mean levels of aggressive behavior in boys, the correlations were notably similar for boys and girls (e.g., aggressive-hyperactivity correlations: 0.51-0.75 boys, 0.47-0.70 girls) and did not vary greatly with respect to age, instrument or cohort. Thus, teacher-rated aggressive behavior rarely occurs in isolation; boys and girls with problems of aggressive behavior likely require help with other behavioral and emotional problems. Important to note, higher aggressive behavior is not only associated with higher amounts of other externalizing and internalizing problems but also with lower levels of prosocial behavior.

}, doi = {10.1371/journal.pone.0238667}, author = {Whipp, Alyce M and Vuoksimaa, Eero and Bolhuis, Koen and de Zeeuw, Eveline L and Korhonen, Tellervo and Mauri, Matteo and Pulkkinen, Lea and Rimfeld, Kaili and Rose, Richard J and van Beijsterveldt, Catharina Toos E M and Bartels, Meike and Plomin, Robert and Tiemeier, Henning and Kaprio, Jaakko and Boomsma, Dorret I} } @article {421, title = {The (broad-sense) genetic correlations among four measures of inattention and hyperactivity in 12 year Olds}, journal = {Behavior Genetics}, volume = {50}, year = {2020}, pages = {273{\textendash}288}, abstract = {

We estimated the genetic covariance matrix among four inattention (INATT) and four hyperactivity (HYP) measures in the classical twin design. Data on INATT and HYP symptom counts were obtained in mono- and dizygotic twin pairs (N = 1593) with an average age of 12.2 years (sd = .51). We analyzed maternal ratings of INATT and HYP based on the Conners\&$\#$39; Parent Rating Scale (CPRS), the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN), and teacher ratings based on the Conners\&$\#$39; Teacher rating scale (CTRS) and the ASEBA Teacher Rating Form (TRF). Broad-sense heritabilities, corrected for the main effects of sex and for random teacher rater effects, were large (ranging from .658 to .912). The results reveal pervasive and strong broad-sense genetic effects on INATT and HYP phenotypes with the phenotypic covariance among the phenotypes largely due to correlated genetic effects. Specifically between 79.9 and 99.9\% of the phenotypic covariance among the HYP measures, and between 81.0 and 93.5\% of the INATT measures are attributable to broad-sense genetic effects. Overall, the present results, pertaining to the broad-sense heritabilities and shared genetic effects, support the current genome-wide association meta-analytic approach to identifying pleiotropic genetic variants.

}, keywords = {ADHD, Genetic correlation, Hyperactivity, Inattention, Multivariate genetic model, Twin design}, doi = {10.1186/s12966-019-0779-4}, author = {Dolan, Conor V and de Zeeuw, Eveline L and Zayats, Tetyana and van Beijsterveldt, C E M and Boomsma, Dorret I} } @article {429, title = {Out of control: Examining the association between family conflict and self-control in adolescence in a genetically sensitive design}, journal = {Journal of the American Academy of Child \& Adolescent }, volume = {59}, year = {2020}, pages = {254{\textendash}262}, abstract = {

OBJECTIVE: Family conflict is associated with low self-control in adolescence. Thus far research about the direction of this association is inconclusive. In this study, we sort out whether this association reflects a causal effect or whether it is explained by a common underlying cause, including genetic factors.

METHOD: In twin data, we fitted a series of causal models, and compared models for the association of family conflict and self-control including reciprocal causation, unidirectional causation from family conflict to low self-control, unidirectional causation from low self-control to family conflict, and common genetic susceptibility. We included data from a large sample of twins aged 14 years (N = 9,173), all enrolled in the Netherlands Twin Register.

RESULTS: The results suggested a unidirectional pathway model in which family conflict leads to low self-control in adolescence, with genetic factors also playing a role in explaining the association.

CONCLUSION: Adolescents experiencing family conflict are at risk for showing hampered self-control capacities, with family conflict being a robust predictor of low self-control through common genetic factors but also through direct causal influences.

}, keywords = {environment, family conflict, genetics, self-control, twins}, doi = {10.1016/j.jaac.2019.02.017}, author = {Willems, Yayouk E and de Zeeuw, Eveline L and van Beijsterveldt, Catharina E M and Boomsma, Dorret I and Bartels, Meike and Finkenauer, Catrin} } @article {426, title = {Urinary Amine and organic acid metabolites evaluated as markers for childhood aggression: The ACTION biomarker study}, journal = {Frontiers in Psychiatry}, volume = {11}, year = {2020}, pages = {165}, abstract = {

Biomarkers are of interest as potential diagnostic and predictive instruments in personalized medicine. We present the first urinary metabolomics biomarker study of childhood aggression. We aim to examine the association of urinary metabolites and neurotransmitter ratios involved in key metabolic and neurotransmitter pathways in a large cohort of twins (N = 1,347) and clinic-referred children (N = 183) with an average age of 9.7 years. This study is part of ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies), in which we developed a standardized protocol for large-scale collection of urine samples in children. Our analytical design consisted of three phases: a discovery phase in twins scoring low or high on aggression (N = 783); a replication phase in twin pairs discordant for aggression (N = 378); and a validation phase in clinical cases and matched twin controls (N = 367). In the discovery phase, 6 biomarkers were significantly associated with childhood aggression, of which the association of O-phosphoserine ($\beta$ = 0.36; SE = 0.09; p = 0.004), and gamma-L-glutamyl-L-alanine ($\beta$ = 0.32; SE = 0.09; p = 0.01) remained significant after multiple testing. Although non-significant, the directions of effect were congruent between the discovery and replication analyses for six biomarkers and two neurotransmitter ratios and the concentrations of 6 amines differed between low and high aggressive twins. In the validation analyses, the top biomarkers and neurotransmitter ratios, with congruent directions of effect, showed no significant associations with childhood aggression. We find suggestive evidence for associations of childhood aggression with metabolic dysregulation of neurotransmission, oxidative stress, and energy metabolism. Although replication is required, our findings provide starting points to investigate causal and pleiotropic effects of these dysregulations on childhood aggression.

}, keywords = {amines, biomarkers, childhood aggression, metabolites, metabolomics, neurotransmitters, organic acids, oxidative stress}, doi = {10.3389/fpsyt.2020.00165}, author = {Hagenbeek, Fiona A and Roetman, Peter J and Pool, Ren{\'e} and Kluft, Cornelis and Harms, Amy C and van Dongen, Jenny and Colins, Olivier F and Talens, Simone and van Beijsterveldt, Catharina E M and Vandenbosch, Marjolein M L J Z and de Zeeuw, Eveline L and D{\'e}jean, S{\'e}bastien and Fanos, Vassilios and Ehli, Erik A and Davies, Gareth E and Hottenga, Jouke Jan and Hankemeier, Thomas and Bartels, Meike and Vermeiren, Robert R J M and Boomsma, Dorret I} } @article {418, title = {Genetic and environmental influences on different forms of bullying perpetration, bullying victimization, and their co-occurrence}, journal = {Behavior Genetics}, volume = {49}, year = {2019}, pages = {432{\textendash}443}, abstract = {

Bullying comes in different forms, yet most previous genetically-sensitive studies have not distinguished between them. Given the serious consequences and the high prevalence of bullying, it is remarkable that the aetiology of bullying and its different forms has been under-researched. We present the first study to investigate the genetic architecture of bullying perpetration, bullying victimization, and their co-occurrence for verbal, physical and relational bullying. Primary-school teachers rated 8215 twin children on bullying perpetration and bullying victimization. For each form of bullying, we investigated, through genetic structural equation modelling, the genetic and environmental influences on being a bully, a victim or both. 34\% of the children were involved as bully, victim, or both. The correlation between being a bully and being a victim varied from 0.59 (relational) to 0.85 (physical). Heritability was \  70\% for perpetration and \  65\% for victimization, similar in girls and boys, yet both were somewhat lower for the relational form. Shared environmental influences were modest and more pronounced among girls. The correlation between being a bully and being a victim was explained mostly by genetic factors for verbal (\  71\%) and especially physical (\  77\%) and mostly by environmental factors for relational perpetration and victimization (\  60\%). Genes play a large role in explaining which children are at high risk of being a victim, bully, or both. For victimization this suggests an evocative gene-environment correlation: some children are at risk of being exposed to bullying, partly due to genetically influenced traits. So, genetic influences make some children more vulnerable to become a bully, victim or both.

}, keywords = {Bully-victims, Bullying, heritability, School, twins, Victimization}, doi = {10.1007/s10519-019-09968-5}, author = {Veldkamp, Sabine A M and Boomsma, Dorret I and de Zeeuw, Eveline L and van Beijsterveldt, Catharina E M and Bartels, Meike and Dolan, Conor V and van Bergen, Elsje} } @article {403, title = {Why do children read more? The influence of reading ability on voluntary reading practices}, journal = {Journal of Child Psychology and Psychiatry}, volume = {59}, year = {2018}, pages = {1205{\textendash}1214}, abstract = {

BACKGROUND: This study investigates the causal relationships between reading and print exposure and investigates whether the amount children read outside school determines how well they read, or vice versa. Previous findings from behavioural studies suggest that reading predicts print exposure. Here, we use twin-data and apply the behaviour-genetic approach of direction of causality modelling, suggested by Heath et al. (), to investigate the causal relationships between these two traits.

METHOD: Partial data were available for a large sample of twin children (N = 11,559) and 262 siblings, all enrolled in the Netherlands Twin Register. Children were assessed around 7.5 years of age. Mothers completed questionnaires reporting children\&$\#$39;s time spent on reading activities and reading ability. Additional information on reading ability was available through teacher ratings and performance on national reading tests. For siblings reading test, results were available.

RESULTS: The reading ability of the twins was comparable to that of the siblings and national norms, showing that twin findings can be generalized to the population. A measurement model was specified with two latent variables, Reading Ability and Print Exposure, which correlated .41. Heritability analyses showed that Reading Ability was highly heritable, while genetic and environmental influences were equally important for Print Exposure. We exploited the fact that the two constructs differ in genetic architecture and fitted direction of causality models. The results supported a causal relationship running from Reading Ability to Print Exposure.

CONCLUSIONS: How much and how well children read are moderately correlated. Individual differences in print exposure are less heritable than individual differences in reading ability. Importantly, the present results suggest that it is the children\&$\#$39;s reading ability that determines how much they choose to read, rather than vice versa.

}, keywords = {behaviour-genetics, causal modelling, Direction of causality models, print exposure, reading skills, twin studies}, doi = {10.1111/jcpp.12910}, author = {van Bergen, Elsje and Snowling, Margaret J and de Zeeuw, Eveline L and van Beijsterveldt, Catharina E M and Dolan, Conor V and Boomsma, Dorret I} }