Shared genetic architecture of reading and attention disorders using genomic structural equation modeling

Reading disorder (RD), characterized by difficulties in reading, is the most common learning disability and frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD), suggesting shared genetic underpinnings. To investigate their genetic overlap, we leveraged summary statistics from large-scale genome-wide association studies (GWASs) of reading assessment scores and ADHD diagnosis using genomic structural equation modeling. We modeled a common genetic factor capturing shared genetic influences between reading-related traits and ADHD. GWAS of this common factor revealed a pleiotropic locus on chromosome 12 (rs7969091, $\beta$ = -0.035, $p$ = 3.86 × 10^-8). Transcriptome-wide structural equation modeling analysis identified associations with tissue-specific expression of RHEBL1 and LMBR1L within the same locus as GWAS hit. Genetic correlation analyses showed significant correlations of the common factor with six psychiatric disorders (r_g = -0.47 to 0.24) and six behavioral traits (r_g = 0.31 to 0.74). Our findings provide novel insights into the shared genetic underpinnings of RD and ADHD.