A meta-analysis of genetic effects on neurodevelopmental disorders and co-occurring conditions

Gidziela, A. and Ahmadzadeh, Y.I. and Michelini, G. and Allegrini, A.G. and Agnew-Blais, J. and Lau, L.Y. and Duret, M. and Procopio, F. and Daly, E. and Ronald, Angelica and Rimfeld, K. and Malanchini, M. (2023) A meta-analysis of genetic effects on neurodevelopmental disorders and co-occurring conditions. Nature Human Behaviour , ISSN 2397-3374.

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.

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