No abstract

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs), their co-occurrence, and co-occurrence with other conditions during childhood and adolescence remains incomplete. This meta-analysis bridges gaps in our knowledge. First, we meta-analysed the literature on the relative contribution of genetic and environmental factors to NDDs. Second, we considered the literature on the overlap between different NDD categories. Lastly, we synthesized the literature on the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). We performed multilevel, random-effects meta-analyses on 296 independent studies, including over 4 million children and adolescents. We found all NDDs to be substantially heritable (family-based heritability (h2) = 0.66; SNP h2 = 0.19). Meta-analytic genetic correlations between NDDs, and between NDDs and DICCs were moderate to strong. However, given the paucity of available studies covering the co-occurrence of NDDs and DICCs, these could only be estimated for a few disorders. While our work provides direct evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.

Most research on individual differences in performance on tests of cognitive ability focuses on general cognitive ability (g), the highest level in the three-level Cattell-Horn-Carroll (CHC) hierarchical model of intelligence. About 50% of the variance of g is due to inherited DNA differences (heritability) which increases across development. Much less is known about the genetics of the middle level of the CHC model, which includes 16 broad factors such as fluid reasoning, processing speed, and quantitative knowledge. We provide a meta-analytic review of 863,041 monozygotic-dizygotic twin comparisons from 80 publications for these middle-level factors, which we refer to as specific cognitive abilities (SCA). Twin comparisons were available for 11 of the 16 CHC domains. The average heritability across all SCA is 55%, similar to the heritability of g. However, there is substantial differential heritability and the SCA do not show the dramatic developmental increase in heritability seen for g. We also investigated SCA independent of g (g-corrected SCA, which we refer to as SCA.g). A surprising finding is that SCA.g remain substantially heritable (53% on average), even though 25% of the variance of SCA that covaries with g has been removed. Our review frames expectations for genomic research that will use polygenic scores to predict SCA and SCA.g. Genome-wide association studies of SCA.g are needed to create polygenic scores that can predict SCA profiles of cognitive abilities and disabilities independent of g. These could be used to foster children's cognitive strengths and minimise their weaknesses.

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs), their co-occurrence, and co-occurrence with other conditions during childhood and adolescence remains incomplete. This meta-analysis bridges gaps in our knowledge. First, we meta-analysed the literature on the relative contribution of genetic and environmental factors to NDDs. Second, we considered the literature on the overlap between different NDD categories. Lastly, we synthesized the literature on the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). We performed multilevel, random-effects meta-analyses on 296 independent studies, including over 4 million children and adolescents. We found all NDDs to be substantially heritable (family-based heritability (h2) = 0.66; SNP h2 = 0.19). Meta-analytic genetic correlations between NDDs, and between NDDs and DICCs were moderate to strong. However, given the paucity of available studies covering the co-occurrence of NDDs and DICCs, these could only be estimated for a few disorders. While our work provides direct evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.