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

Vainieri, Isabella, Martin, Joanna, Rommel, Anna-Sophie, Asherson, Philip, Banaschewski, Tobias, Buitelaar, Jan, Cormand, Bru, Crosbie, Jennifer, Faraone, Stephen V., Franke, Barbara, Loo, Sandra K., Miranda, Ana, Manor, Iris, Oades, Robert D., Purves, Kirstin L., Ramos-Quiroga, J. Antoni, Ribasés, Marta, Roeyers, Herbert, Rothenberger, Aribert, Schachar, Russell, Sergeant, Joseph, Steinhausen, Hans-Christoph, Vuijk, Pieter J., Doyle, Alysa E. and Kuntsi, Jonna 2021. Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments. Psychological Medicine 10.1017/S0033291720005218

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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.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/)
Publisher: Cambridge University Press
ISSN: 0033-2917
Date of First Compliant Deposit: 5 February 2021
Date of Acceptance: 8 December 2020
Last Modified: 08 Feb 2021 10:00
URI: http://orca.cardiff.ac.uk/id/eprint/138291

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