Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Isabella Vainieri, Joanna Martin, Anna-Sophie Rommel, Philip Asherson, Tobias Banaschewski, Jan Buitelaar, Bru Cormand, Jennifer Crosbie, Stephen V. Faraone, Barbara Franke, Sandra K. Loo, Ana Miranda, Iris Manor, Robert D. Oades, Kirstin Purves, Josep Antoni Ramos-Quiroga, Marta Ribases, Herbert Roeyers, Aribert Rothenberger, Russell SchacharJoseph Sergeant, Hans Christoph Steinhausen, Pieter J. Vuijk, Alysa E Doyle, Jonna Kuntsi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background

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).

Methods

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.

Results

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).

Conclusions

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.

Original languageEnglish
JournalPsychological Medicine
Early online date3 Feb 2021
DOIs
Publication statusE-pub ahead of print - 3 Feb 2021

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