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Rare Variants in Three Genes Linked to Up to 15-Fold Higher ADHD Risk

A Nature study connects ultra-rare coding changes to specific neuronal pathways with real-world cognitive and socioeconomic effects.

Overview

  • The exome-sequencing analysis assessed 8,895 people with ADHD and about 54,000 controls, with outcomes linked through Danish national registries.
  • MAP1A, ANO8 and ANK2 carried very rare deleterious variants associated with odds ratios ranging from 5.55 to 15.13 for ADHD.
  • Cell-type and developmental analyses implicated dopaminergic and GABAergic neurons from fetal stages into adulthood.
  • Among adults with ADHD, each rare deleterious variant correlated with an average 2.25-point lower IQ and with reduced educational attainment and socioeconomic status.
  • Protein network analyses connected the three genes to pathways implicated in autism and schizophrenia, and the authors highlighted 17 additional likely causal genes and the need for larger, mechanistic studies.