Along with polygenicity, selection and evolutionary pressures may be an important feature of the architecture of ADHD genetics. We observe that ADHD risk variants are strongly enriched in genomic regions conserved in mammals94, and constrained genes likely to be intolerant of loss-of-function mutations91 are associated with ADHD. We also find that common variant risk for ADHD is genetically correlated with having children younger and having more children, in line with epidemiological findings of increased risky sexual behaviour95–97 and increased risk of ADHD for children born to young parents98–100. Given the phenotypic101,102 and genetic103 correlation of ADHD with reduced educational attainment, positive selective pressure on the genetics of ADHD would be consistent with recent work suggesting that variants associated with educational attainment are under negative selection in Iceland104. Future studies of fecundity and the role of rare and de novo variants in ADHD may provide more insight on selective pressures in ADHD-associated loci.
