Integrating genomics and transcriptomics: Towards deciphering ADHD

Eur Neuropsychopharmacol. 2021 Mar:44:1-13. doi: 10.1016/j.euroneuro.2021.01.002. Epub 2021 Jan 23.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable condition that represents the most common neurodevelopmental disorder in childhood, persisting into adulthood in around 40-65% of the cases. ADHD is characterised by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity. Mounting evidence points towards ADHD having a strong genetic component and the first genome-wide significant findings have recently been reported. However, the functional characterization of variants unravelled by genome-wide association studies (GWAS) is challenging. Likewise, gene expression profiling studies have also been undertaken and novel integrative approaches combining genomic and transcriptomic data are starting to be conducted, which offers an exciting way that might provide a more informative insight towards the genetic architecture of ADHD. In this review, we summarised current knowledge on genomics, transcriptomics and integrative approaches in ADHD, focusing on GWAS and GWAS meta-analyses (GWAS-MA)- as genomics analyses- microarray and RNA-seq- as transcriptomics analyses-, and studies integrating genomics and transcriptomics data. In addition, current strengths and limitations of such approaches are discussed and further research avenues are proposed in order to face unsolved issues. Although important progress has been made, there is still a long way ahead to elucidate the biological mechanisms of ADHD, which eventually may lead to more personalized approaches in the future. Large- scale research efforts and new technological and statistical approaches are envisaged as important means towards deciphering ADHD in the upcoming years.

Keywords: ADHD; Expression quantitative trait loci (eQTL); Genetics; Genome-wide association studies (GWAS); Transcriptome-wide association studies (TWAS); Transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Impulsive Behavior
  • Transcriptome