A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).

The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.

When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).

We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.

We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.

Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).

Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.