Abstract
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.
Highlights
A recent case-control genome-wide association study (GWAS) identified, for the first time, 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD) (Demontis et al, 2019)
This is one of the largest studies investigating the association between ADHD Polygenic risk scores (PRS) and cognitive impairments in individuals diagnosed with ADHD
Combining our samples in meta-analyses, our results show that polygenic risk for clinically diagnosed ADHD is positively associated with higher reaction time variability (RTV), but not with commission errors (CE) as measured by Go/No Go tasks
Summary
A recent case-control genome-wide association study (GWAS) identified, for the first time, 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD) (Demontis et al, 2019). This GWAS enables further genetic investigations using polygenic risk scores (PRS), which are calculated for each individual by computing the sum of their risk alleles across the genome, weighted by effect sizes (Choi, Mak, & O’Reilly, 2018). 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 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). 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
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