Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy

This study investigates the genetic mechanisms underlying the discordant polygenic associations between educational attainment (EA), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using multivariable regression analyses of genome-wide summary statistics, the researchers found that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA is discordant for ASD and ADHD risk, indicating independent effects. Single-variant level analysis suggests either biological pleiotropy or co-localization of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, the results point to a polygenic form of pleiotropy contributing to the genome-wide correlation between ASD and ADHD, consistent with effect cancellation across EA-related regions.

Ellen Verhoef, Jakob Grove, Chin Yang Shapland, Ditte Demontis, Stephen Burgess, Dheeraj Rai, Anders D. Børglum, Beate St Pourcain