Association between polygenic risk scores for attention-deficit hyperactivity disorder and educational and cognitive outcomes in the general population

Abstract

Background: Children with a diagnosis of attention-deficit hyperactivity disorder ADHD) have lower cognitive ability and are at risk of adverse educational outcomes; ADHD genetic risks have been found to predict childhood cognitive ability and other neurodevelopmental traits in the general population; thus genetic risks might plausibly also contribute to cognitive ability later in development and to educational underachievement.

Methods: We generated ADHD polygenic risk scores in the Avon Longitudinal Study of Parents and Children participants (maximum N : 6928 children and 7280 mothers) based on the results of a discovery clinical sample, a genome-wide association study of 727 cases with ADHD diagnosis and 5081 controls. We tested if ADHD polygenic risk scores were associated with educational outcomes and IQ in adolescents and their mothers.

Results: High ADHD polygenic scores in adolescents were associated with worse educational outcomes at Key Stage 3 [national tests conducted at age 13-14 years; β = -1.4 (-2.0 to -0.8), P = 2.3 × 10 -6 ), at General Certificate of Secondary Education exams at age 15-16 years (β = -4.0 (-6.1 to -1.9), P = 1.8 × 10 -4 ], reduced odds of sitting Key Stage 5 examinations at age 16-18 years [odds ratio (OR) = 0.90 (0.88 to 0.97), P = 0.001] and lower IQ scores at age 15.5 [β = -0.8 (-1.2 to -0.4), P = 2.4 × 10 -4 ]. Moreover, maternal ADHD polygenic scores were associated with lower maternal educational achievement [β = -0.09 (-0.10 to -0.06), P = 0.005] and lower maternal IQ [β = -0.6 (-1.2 to -0.1), P = 0.03].

Conclusions: ADHD diagnosis risk alleles impact on functional outcomes in two generations (mother and child) and likely have intergenerational environmental effects.

Keywords: Attention-deficit/hyperactivity disorder (ADHD); Avon Longitudinal Study of Parents and Children (ALSPAC); cognitive traits; education; polygenic risk scores.

Figure 1.

Structural Equation Modelling Analysis Based on Sobel-Goodman Test of Mediation in ALSPAC Children with GCSE Results as Outcome and IQ as Mediator.

Figure 2.

Structural Equation Modelling Analysis Based on Sobel-Goodman Test of Mediation in ALSPAC Children with GCSE Results as Outcome and ADHD symptoms as Mediator.