Fig. 2: Genetic relationships between ADHD, educational attainment and literacy-related and language-related abilities

ADHD Attention-Deficit/Hyperactivity Disorder, EA educational attainment, LRAs literacy and language-related abilities, PGC Psychiatric Genomics Consortium, iPSYCH The Lundbeck Foundation Initiative for Integrative Psychiatric Research; SSGAC Science Genetic Association Consortium, ALSPAC Avon Longitudinal Study of Parents And Children, MVR multivariable regression. a Hypothesised biological model of genetic relationships between ADHD, EA, and LRAs reflecting complex, pleiotropic and reciprocal genetic links that prevent causal inferences. b Schematic MVR model assessing polygenic ADHD-LRA overlap independent of and shared with genetic effects for EA. c MVR estimates of ADHD-specific effects independent of EA and ADHD effects shared with EA on LRAs using standardised ADHD instruments: Sets of conservative (P < 5 × 10^-8) and subthreshold (P < 0.0015) ADHD instruments were extracted from ADHD (PGC + iPSYCH), EA (SSGAC) and LRAs (ALSPAC) GWAS summary statistics. ADHD-specific effects independent of EA (β_ADHD) and ADHD effects shared with EA (β_EA) on LRAs were estimated with MVRs. To compare the magnitude of β_ADHD and β_EA, MVR analyses were conducted using standardised regression estimates (Supplementary Methods). β_ADHD estimates measure the change in LRA Z-score per Z-score in ADHD liability. β_EA estimates measure the change in LRA Z-scores per Z-score in missing school years. MVR estimates based on raw genetic effect estimates are provided in Table 3. Pooled estimates for reading, spelling and global LRA measures (Table 1) were obtained through random-effects meta-regression. Only effects passing the experiment-wide significance threshold (P < 0.007) are shown with corresponding 95% confidence intervals. There is no causality inferred