Genetic influences on neurodevelopmental disorders and their overlap with co-occurring conditions in childhood and adolescence: A meta-analysis

Abstract

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.

Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review

“…Moreover, the lack of evidence of transdiagnosticity from GWAS should be considered with caution, given the small sample size for neurodevelopmental disorders (particularly learning disorders)­ and meta‐analytic evidence indicating large genetic correlations between most neurodevelopmental disorders 56 . Indeed, cross‐disorder genetic correlation estimates clearly show that there are substantial shared common genetic risks (e.g., across ADHD and ASD) and therefore future studies of specific SNPs that are implicated in multiple disorders will need to be identified through multi‐disorder analyses 32 .…”