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.

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.

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%.

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.

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,<sup>5Ronald A., Larsson H., Anckarsäter H., Lichtenstein P. Symptoms of autism and ADHD: a Swedish twin study examining their overlap J Abnorm Psychol 2014 ;  123 : 440-451 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 6Grove J., Ripke S., Als T.D., e al. Identification of common genetic risk variants for autism spectrum disorder Nat Genet 2019 ;  51 : 431-444 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 7Stergiakouli E., Davey Smith G., Martin J., e al. Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development Mol Autism 2017 ;  8 : 18

Cliccare qui per andare alla sezione Riferimenti, 8Taylor M.J., Charman T., Ronald A. Where are the strongest associations between autistic traits and traits of ADHD? Evidence from a community-based twin study Eur Child Adolesc Psychiatry 2015 ;  24 : 1129-1138 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 9Ronald A., Edelson L.R., Asherson P., Saudino K.J. Exploring the relationship between autistic-like traits and ADHD behaviors in early childhood: findings from a community twin study of 2-year-olds J Abnorm Child Psychol 2010 ;  38 : 185-196 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 10Ronald A., Simonoff E., Kuntsi J., Asherson P., Plomin R. Evidence for overlapping genetic influences on autistic and ADHD behaviours in a community twin sample J Child Psychol Psychiatry 2008 ;  49 : 535-542 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> tobacco and alcohol use,^11,12 and depressive and hypomanic symptoms.<sup>13Eilertsen E.M., Hannigan L.J., McAdams T.A., e al. Parental prenatal symptoms of depression and offspring symptoms of ADHD: a genetically informed intergenerational stud [published online ahead of print April 26, 2020]. J Atten Disordhttps://doi.org/10.1177/1087054720914386

Cliccare qui per andare alla sezione Riferimenti, 14Cross-Disorder Group of the Psychiatric Genomics Consortium genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders Cell 2019 ;  179 : 1469-1482

Cliccare qui per andare alla sezione Riferimenti, 15Hosang G.M., Lichtenstein P., Ronald A., Lundström S., Taylor M.J. Association of genetic and environmental risks for attention-deficit/hyperactivity disorder with hypomanic symptoms in youths JAMA Psychiatry 2019 ;  76 : 1150-1158 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>