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Genome-Wide Analysis Sheds Light on Genetics of ADHD

A study appearing in this week's Nature Genetics has uncovered dozens of new attention-deficit hyperactivity disorder (ADHD) risk loci and numerous candidate causal genes, showing a link between the condition and other psychiatric disorders. ADHD affects around 5 percent of children and oftentimes persists into adulthood. It also has a major genetic component, yet the complex polygenic architecture of the condition makes it difficult to identify its underlying biological causes. In the new study, an international research team led by investigators at Aarhus University in Denmark conducted a genome-wide association study meta-analysis of 38,691 individuals with ADHD and 186,843 controls. They identified 27 genome-wide significant loci, highlighting 76 potential risk genes that are enriched among those expressed in early brain development. Using exome-sequencing data from 17,896 individuals, the study's authors identify an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants. Further analysis, meanwhile, shows ADHD to be highly polygenic and influenced by thousands of variants, the vast majority of which also influence other psychiatric disorders. The researchers also showed that common-variant ADHD risk affects complex cognition such as verbal reasoning. "Overall, the results advance our understanding of the underlying biology of ADHD and reveal new aspects of the polygenic architecture of ADHD, its relationship with other phenotypes and its impact on cognitive domains," the authors write.