TY - JOUR
T1 - Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments
AU - Vainieri, Isabella
AU - Martin, Joanna
AU - Rommel, Anna-Sophie
AU - Asherson, Philip
AU - Banaschewski, Tobias
AU - Buitelaar, Jan
AU - Cormand, Bru
AU - Crosbie, Jennifer
AU - Faraone, Stephen V
AU - Franke, Barbara
AU - Loo, Sandra K
AU - Miranda, Ana
AU - Manor, Iris
AU - Oades, Robert D
AU - Purves, Kirstin L
AU - Ramos-Quiroga, J Antoni
AU - Ribasés, Marta
AU - Roeyers, Herbert
AU - Rothenberger, Aribert
AU - Schachar, Russell
AU - Sergeant, Joseph
AU - Steinhausen, Hans-Christoph
AU - Vuijk, Pieter J
AU - Doyle, Alysa E
AU - Kuntsi, Jonna
PY - 2022/10/3
Y1 - 2022/10/3
N2 - 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 (R= 0.011, β = 0.088, p = 0.02) but not for CE (R= 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.
AB - 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 (R= 0.011, β = 0.088, p = 0.02) but not for CE (R= 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.
KW - ADHD
KW - attention
KW - cognition
KW - inhibition
KW - polygenic risk scores
KW - reaction time variability
UR - http://www.scopus.com/inward/record.url?scp=85100404115&partnerID=8YFLogxK
U2 - 10.1017/S0033291720005218
DO - 10.1017/S0033291720005218
M3 - Journal article
C2 - 33531098
SN - 0033-2917
VL - 52
SP - 3150
EP - 3158
JO - Psychological Medicine
JF - Psychological Medicine
IS - 14
ER -