Abstract
BackgroundThe association patterns of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) with educational attainment (EA) are complex; children with ADHD and ASD are at risk of poor academic outcomes, and parental EA has been associated with risk of ADHD/ASD in the offspring. Little is known on the causal links between ADHD, ASD, EA and the potential contribution of cognitive ability.MethodsUsing the latest genome-wide association studies (GWAS) summary data on ADHD, ASD and EA, we applied two-sample Mendelian randomization (MR) to assess the effects of genetic liability to ADHD and ASD on EA. Reverse direction analyses were additionally performed. Multivariable MR was performed to estimate any effects independent of cognitive ability.ResultsGenetic liability to ADHD had a negative effect on EA, independently of cognitive ability (MVMRIVW: -1.7 months of education per doubling of genetic liability to ADHD; 95% CI: -2.8 to -0.7), whereas genetic liability to ASD a positive effect (MVMRIVW: 30 days per doubling of the genetic liability to ASD; 95% CI: 2 to 53). Reverse direction analyses suggested that genetic liability to higher EA had an effect on lower risk of ADHD, independently of cognitive ability (MVMRIVWOR: 0.33 per SD increase; 95% CI: 0.26 to 0.43) and increased risk of ASD (MRIVWOR: 1.51 per SD increase; 95% CI: 1.29 to 1.77), which was partly explained by cognitive ability (MVMRIVWOR per SD increase: 1.24; 95%CI: 0.96 to 1.60).ConclusionsGenetic liability to ADHD and ASD is likely to affect educational attainment, independently of underlying cognitive ability.
Highlights
We used Steiger filtering in order to exclude the possibility that the direction of the identified effects was influenced by the large sample size and power of the educational attainment GWAS or the strong genetic correlations between ADHD, ASD and educational attainment[8]
Table S2a.Harmonised instruments used in the MR analyses investigating the causal effect of genetic liability to ADHD on educational attainment
Table S2b.Harmonised instruments used in the MR analyses investigating the causal effect of genetic liability to ASD on educational attainment
Summary
Sensitivity Analyses to test for horizontal pleiotropy and the robustness of the causal effect estimates. We conducted weighted median MR which provides an estimate of effect even when only 50% of the genetic variants included in the analysis are valid instruments for the exposure[5]. We performed weighted mode MR which provides an effect estimate based on the assumption that the most common effect of the genetic variants stems from valid instruments[6].
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