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

Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments. Vainieri, I., Martin, J., Rommel, A., Asherson, P., Banaschewski, T., Buitelaar, J., Cormand, B., Crosbie, J., Faraone, S. V., Franke, B., Loo, S. K., Miranda, A., Manor, I., Oades, R. D., Purves, K. L., Ramos-Quiroga, J. A., Ribasés, M., Roeyers, H., Rothenberger, A., Schachar, R., Sergeant, J., Steinhausen, H., Vuijk, P. J., Doyle, A. E., & Kuntsi, J. Psychological Medicine, Cambridge University Press, February, 2021.

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BackgroundA 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).MethodsThe 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.ResultsWhen 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 \textgreater 0.10).ConclusionsWe 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.

@article{vainieriPolygenicAssociationAttentiondeficit2021,
	title = {Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments},
	issn = {0033-2917, 1469-8978},
	url = {https://www.cambridge.org/core/journals/psychological-medicine/article/polygenic-association-between-attentiondeficithyperactivity-disorder-liability-and-cognitive-impairments/AC78FA587B7FED44B678F6CC9CCB7AB3},
	doi = {10.1017/S0033291720005218},
	abstract = {BackgroundA 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).MethodsThe 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.ResultsWhen 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 {\textgreater} 0.10).ConclusionsWe 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.},
	language = {en},
	urldate = {2022-08-02},
	journal = {Psychological Medicine},
	publisher = {Cambridge University Press},
	author = {Vainieri, Isabella and Martin, Joanna and Rommel, Anna-Sophie and Asherson, Philip and Banaschewski, Tobias and Buitelaar, Jan and Cormand, Bru and Crosbie, Jennifer and Faraone, Stephen V. and Franke, Barbara and Loo, Sandra K. and Miranda, Ana and Manor, Iris and Oades, Robert D. and Purves, Kirstin L. and Ramos-Quiroga, J. Antoni and Ribasés, Marta and Roeyers, Herbert and Rothenberger, Aribert and Schachar, Russell and Sergeant, Joseph and Steinhausen, Hans-Christoph and Vuijk, Pieter J. and Doyle, Alysa E. and Kuntsi, Jonna},
	month = feb,
	year = {2021},
	keywords = {ADHD, JC, RJS, attention, cognition, inhibition, open access, polygenic risk scores, reaction time variability},
	pages = {1--9},
}

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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).MethodsThe 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.ResultsWhen 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). 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Results across sites were combined via random effect meta-analyses.ResultsWhen 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). 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