Shared genetics between ADHD and reading/language abilities: Genome-wide correlations, stratified enrichment,...

Attention-deficit/hyperactivity disorder (ADHD) and language/reading difficulties frequently co-occur. The extent of shared genetic architecture remains incompletely defined. We investigated genome-wide overlap between ADHD and four core skills: word reading, nonword reading, spelling, and phoneme awareness.

We integrated genome-wide association study (GWAS) summary statistics from the Psychiatric Genomics Consortium for ADHD (38,691 cases; 186,843 controls) and from the GenLang Consortium for language-related traits (n = 13,633-33,959). We performed linkage disequilibrium score regression (LDSC) to estimate genetic correlations and stratified LDSC to identify enriched genomic annotations. Cross-trait meta-analyses were conducted using MTAG and CPASSOC to identify cross-trait association signals. Mendelian randomization (MR) was applied to assess potential directional relationships.

Genome-wide genetic correlations were negative and significant between ADHD and each reading- and language-related trait (word reading rg = -0.35, p = 1.35 × 10^-16; nonword reading rg = -0.28, p = 2.15 × 10^-9; spelling rg = -0.38, p = 1.03 × 10^-15; phoneme awareness rg = -0.28, p = 2.64 × 10^-6). Partitioned heritability analysis using S-LDSC showed significant enrichment after Benjamini-Hochberg false discovery rate correction (BH-FDR), concentrated in conserved or constrained annotations such as Genomic Evolutionary Rate Profiling and phastCons. Cross-trait analyses (MTAG and CPASSOC) identified loci associated with ADHD and each skill, 6 for word reading, 7 for spelling, 7 for phoneme awareness, and 4 suggestive loci for nonword reading (dual-method p < 5 × 10^-6); several map near neurodevelopmental genes including DCC, MEF2C, and ST3GAL3. Bidirectional MR findings were consistent with a potential directional contribution of ADHD genetic liability to poorer reading/language performance, with no clear evidence supporting the reverse direction under standard MR assumptions.

ADHD and language/reading abilities share a substantial polygenic overlap with convergent signals in neuronal regulatory annotations. These genome-wide findings support a transdiagnostic framework linking attention and literacy-related skills, while indicating that causal and clinical interpretations should remain cautious given the modest effect sizes and limited variance captured by current GWAS resources.