New genetic variants contributing to severe ADHD

A study of nearly 4 thousand individuals with ADHD and disruptive behaviors has found new variants contributing to the risk of the condition. Most heavily affected genes govern the plasticity of neurons.

Attention deficit hyperactivity disorder (ADHD) was repeatedly linked with various genetic variants. However, subsequent approaches to link genetics with a more severe form of ADHD – coupled with disruptive behavior disorders (DBDs), present in 17-30% of all ADHD carriers – have failed. Now, in the most extensive study of ADHD and DBDs to date, scientists are discovering two places in the human genome, which influence the occurrence of disorders.

The study relied on a well known genome-wide association method (GWAS). 3,802 individuals from Europe and China were compared to 31,305 healthy people. Findings were also compared to previous research on ADHD-only GWAS.

Discovered variants lie in chromosome 1 and chromosome 11, although chromosome 1 appears to be more European-specific. In chromosome 11, common for the whole study, mutations in genes STIM1 and around RRM1 increase the risk of ADHD coupled with DBDs and correlate with aggressive, anti-social behaviors. Those genes seem specific for this combination of disorders, as they were not previously identified in ADHD-only studies.

Researchers also created a polygenic risk score, which can differentiate between individuals with the lowest and highest risk of developed ADHD+DBDs. The odds ratio between them was assessed as 2.48.

The study was not published yet – the results are from preliminary preprint available here: https://www.biorxiv.org/content/10.1101/791160v1

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