Neurocognitive abilities in the general population and composite genetic risk scores for attention-deficit hyperactivity disorder.

Joanna Martin,Anita Thapar,Michael C O'Donovan,Evangelia Stergiakouli,Marian L Hamshere

doi:10.1111/jcpp.12336

Joanna Martin, Anita Thapar + Show 3 more

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https://doi.org/10.1111/jcpp.12336

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Abstract

BackgroundThe genetic architecture of ADHD is complex, with rare and common variants involved. Common genetic variants (as indexed by a composite risk score) associated with clinical ADHD significantly predict ADHD and autistic-like behavioural traits in children from the general population, suggesting that ADHD lies at the extreme of normal trait variation. ADHD and other neurodevelopmental disorders share neurocognitive difficulties in several domains (e.g. impaired cognitive ability and executive functions). We hypothesised that ADHD composite genetic risk scores derived from clinical ADHD cases would also contribute to variation in neurocognitive abilities in the general population.MethodsChildren (N = 6,832) from a UK population cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), underwent neurocognitive testing. Parent-reported measures of their children's ADHD and autistic-like traits were used to construct a behavioural latent variable of ‘neurodevelopmental traits’. Composite genetic risk scores for ADHD were calculated for ALSPAC children based on findings from an independent ADHD case–control genome-wide association study. Structural equation modelling was used to assess associations between ADHD composite genetic risk scores and IQ, working memory, inhibitory control and facial emotion recognition, as well as the latent ‘neurodevelopmental trait’ measure.ResultsThe results confirmed that neurocognitive and neurodevelopmental traits are correlated in children in the general population. Composite genetic risk scores for ADHD were independently associated with lower IQ (β = −.05, p < .001) and working memory performance (β = −.034, p = .013), even after accounting for the relationship with latent neurodevelopmental behavioural trait scores. No associations were found between composite genetic risk scores and inhibitory control or emotion recognition (p > .05).ConclusionsThese findings suggest that common genetic variants relevant to clinically diagnosed ADHD have pleiotropic effects on neurocognitive traits as well as behavioural dimensions in the general population. This further suggests that the well-recognised association between cognition and neurodevelopmental behavioural traits is underpinned at a biological level.

Highlights

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder (Faraone et al, 2005)
Twin studies demonstrate significant co-heritability across neurodevelopmental disorders and traits, including ADHD and autism spectrum disorder (ASD) (Lichtenstein, Carlstro€m, Rastam, Gillberg, & Anckarsa€ter, 2010; Ronald, Simonoff, Kuntsi, Asherson, & Plomin, 2008). These findings suggest that genetic risk variants for ADHD are likely to contribute to multiple neurodevelopmental behavioural traits and disorders
This study finds that common genetic risk variants that predict risk of clinical ADHD diagnosis and that were previously found to predict parent-reported ADHD and social-communication behavioural traits in the general population (Martin et al, 2014b) are associated with lower IQ and working memory in children from the general population

Summary

Introduction

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder (Faraone et al, 2005). Twin studies demonstrate significant co-heritability across neurodevelopmental disorders and traits, including ADHD and ASD (Lichtenstein, Carlstro€m, Rastam, Gillberg, & Anckarsa€ter, 2010; Ronald, Simonoff, Kuntsi, Asherson, & Plomin, 2008) These findings suggest that genetic risk variants for ADHD are likely to contribute to multiple neurodevelopmental behavioural traits and disorders. Conclusions: These findings suggest that common genetic variants relevant to clinically diagnosed ADHD have pleiotropic effects on neurocognitive traits as well as behavioural dimensions in the general population. This further suggests that the well-recognised association between cognition and neurodevelopmental behavioural traits is underpinned at a biological level.

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