Neurodevelopmental disorders have been associated with hearing problems (HP) later in life, but there is limited information regarding their shared biology.

We leveraged large-scale genome-wide datasets to estimate genetic correlation (global and local), polygenic overlap, and locus-specific pleiotropy among HP, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Tourette syndrome (TS). Then, we investigated shared molecular functions, biological processes, and cellular components, and performed a drug-repurposing analysis to identify compounds that may target the pathogenic processes linking neurodevelopmental disorders to HP.

We observed high genetic correlation of HP with ASD (rg = 0.22) and TS (rg = 0.22). With respect to HP-ADHD polygenic overlap, 34% of the causal variants were shared between these conditions, with only 74% of them showing concordant effect directions. We also identified nine chromosomal regions with evidence of ADHD-HP local genetic correlations with pleiotropic effects on other outcomes, such as smoking initiation, brain-imaging phenotypes, and bilirubin levels. With respect to HP-ASD, we observed an inverse local genetic correlation within CD33 chromosomal region. Pleiotropy among HP, ASD, and ADHD was also identified in two variants (rs325485 and rs2207286) included within 95% credible sets related to neuropsychiatric conditions, altered hearing function, and other traits such as risk taking and insomnia. Drug-repurposing analyses identified anisomycin for HP-ASD shared biological mechanisms and five compounds related to HP-ADHD pleiotropy.

Our findings provide evidence that the comorbidity between neurodevelopmental disorders and HP is at least partially due to shared pathogenic processes acting through intrinsic and extrinsic factors.