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Systematic Review: How the Attention-Deficit/Hyperactivity Disorder Polygenic Risk Score Adds to Our Understanding of ADHD and Associated Traits - 22/09/21

Doi : 10.1016/j.jaac.2021.01.019 
Angelica Ronald, PhD a, Nora de Bode, BSc b, Tinca J.C. Polderman, PhD b,
a Birkbeck University of London, United Kingdom 
b Vrije Universiteit Amsterdam, the Netherlands, and Amsterdam UMC, the Netherlands 

Correspondence to Tinca J.C. Polderman, PhD, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 117, Amsterdam, The NetherlandsAmsterdam UMCVrije Universiteit AmsterdamDe Boelelaan 117AmsterdamThe Netherlands

Abstract

Objective

To investigate, by systematically reviewing the literature, whether the attention-deficit/hyperactivity disorder (ADHD) polygenic risk score (PRS) associates with ADHD and related traits in independent clinical and population samples.

Method

PubMed, Embase and PsychoInfo were systematically searched, alongside study bibliographies. Quality assessments were conducted, and a best-evidence synthesis was applied. Studies were excluded when the predictor was not based on the latest ADHD genome-wide association study, when PRS was not based on genome-wide results, or when the study was a review. Initially, 197 studies were retrieved (February 22, 2020), and a second search (June 3, 2020) yielded a further 49 studies. From both searches, 57 studies were eligible, and 44 studies met inclusion criteria.

Results

Included studies were published in the last 3 years. Over 80% of the studies were rated excellent, based on a standardized quality assessment. Evidence of associations between ADHD PRS and the following categories was strong: ADHD, ADHD traits, brain structure, education, externalizing behaviors, neuropsychological constructs, physical health, and socioeconomic status. Evidence for associations with addiction, autism, and mental health were mixed and were, so far, inconclusive. Odds ratios for PRS associating with ADHD ranged from 1.22% to 1.76%; variance explained in dimensional assessments of ADHD traits was 0.7% to 3.3%.

Conclusion

A new wave of high-quality research using the ADHD PRS has emerged. Eventually, symptoms may be partly identified based on PRS, but the current ADHD PRS is useful for research purposes only. This review shows that the ADHD PRS is robust and reliable, associating not only with ADHD but many outcomes and challenges known to be linked to ADHD.

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Resumen

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects approximately 5% of children and 2.5% of adults.1 Decades of past research have established the significant twin heritability of ADHD and family studies demonstrate its high familiality.2,3 More recently, significant single nucleotide polymorphism (SNP) heritability estimates for ADHD have been reported.4 Together this evidence supports the hypothesis that common genetic variants acting additively play a role in the causes of ADHD.3 In addition, twin, family, and molecular genetic studies suggest that these common variants may, to some degree, be shared with other conditions and traits, including autism and autistic traits,5, 6, 7, 8, 9, 10 tobacco and alcohol use,11,12 and depressive and hypomanic symptoms.13, 14, 15

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Key words : attention-deficit/hyperactivity disorder, genetics, neurodevelopment, comorbidity, psychiatry


Esquema


 The authors have reported no funding for this work.
 This article is part of a special series devoted to the subject of subject of child and adolescent attention-deficit/hyperactivity disorder (ADHD). The series covers a range of topics in the area including genetics, neuroimaging, treatment, and others. The series was edited by Guest Editor Jonathan Posner, MD, along with Deputy Editor Samuele Cortese, MD, PhD.
 Author Contributions
 Conceptualization: Ronald, Polderman
 Data curation: de Bode, Polderman
 Formal analysis: Ronald, de Bode, Polderman
 Investigation: Ronald, de Bode, Polderman
 Methodology: Ronald
 Resources: de Bode
 Supervision: Polderman
 Writing – original draft: Ronald, Polderman
 Writing – review and editing: Ronald, Polderman
 Disclosure: Drs. Ronald, Polderman, and Ms. de Bode have reported no biomedical financial interests or potential conflicts of interest.


© 2021  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 60 - N° 10

P. 1234-1277 - octobre 2021 Regresar al número
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