Genome-wide meta-analysis of ADHD symptoms in the adult general population reveals distinct genetics of inattention and hyperactivity-impulsivity

We conducted genome-wide meta-analyses (N = 141,505; Estonian Biobank and Norwegian Mother, Father and Child Cohort Study) with polygenic score-based validation (N = 19,857; Dutch Lifelines cohort) of self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults from the general population. We identified eight genetic loci associated with either total symptoms, inattention or hyperactivity-impulsivity domains. Distinct genetic architectures underlying the two symptom domains were demonstrated by their moderate genetic correlation (r _g =0.35, 95% CI 0.26 to 0.43) and by contrasting genetic association patterns across other phenotypes and medical conditions. Hyperactivity-impulsivity showed stronger genetic links with ADHD diagnosis, negative r _g -s (-0.28 to -0.19) with educational traits, and more associations with diagnoses in electronic health records. Whereas inattention was weakly genetically associated with ADHD diagnosis, showed positive r _g -s (0.24 to 0.29) with educational phenotypes, and fewer links with clinical outcomes. This is the first genome-wide study to detect significant signals associated with adult ADHD symptoms and symptom dimensions.