Development Projects
The association between neurodevelopmental disorders and disruptive, impulse control and conduct disorders
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).
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. Meta-analytic genetic correlations between NDDs were moderate but differed between pairs of disorders. The genetic overlap between NDDs and DICCs was strong but could only be meta-analyzed for a few disorders, highlighting a major gap in our knowledge.
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.
Check out this 5-minute poster presentation where CoDE Lab PhD student and first author, Agnieszka Gidziela, tells us more about our findings:
Isolating transdiagnostic effects to uncover specific genetic profiles in psychiatric disorders
Evidence indicates a great degree of genetic overlap between psychiatric diagnoses. Accounting for these transdiagnostic effects can sharpen research on disorder-specific genetic architecture. Here we isolate genetic effects that are shared across 11 major psychiatric disorders (p factor) to gain further insight into genetic specificity and comorbidity over and above that contributed by the p factor, unique to each psychiatric disorder. After adjusting for transdiagnostic genetic effects, we identified novel SNP associations and some changes in enrichment patterns. We examined genetic correlations among adjusted psychiatric traits as well as relationships with other biobehavioural traits. The landscape of genetic associations between pairs of psychiatric disorders changed substantially, and their genetic correlations with biobehavioural traits showed greater specificity. Isolating transdiagnostic genetic effects across major psychiatric disorders provides a nuanced understanding of disorder-specific genetic architecture and may help guide diagnostic nomenclature and treatment research.
Translational genetics: Investigating the links between impulsivity and psychopathology in humans and zebrafish
This project, in collaboration with Professor Caroline Brennan’s research laboratory at QMUL, examines the genetic association between hypomania/mania and impulsivity, exploring the underlying cell biology.
In this project, we leverage genetic analysis of existing human datasets to determine the genetic relationship between impulsivity and mania/hypomania, identify shared and distinct genetic factors associated with these behaviours and test the hypothesis that there is a causal relationship between the genetics of impulsivity and bipolar disorder. We conduct gene expression pathway analysis to identify the neurobiological processes involved. We combine this analysis of human data with gene expression, behavioural and cell biological analysis in zebrafish to identify developmental and cellular processes contributing to impulse control and bipolar disorder.
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