Genetic association of attention-deficit/hyperactivity disorder with thirteen ocular disorders

Abstract

<p>Purpose: Although attention deficit hyperactivity disorder (ADHD) is linked to elevated risk of various ocular disorders, their genetic association and causality remain unclear. Methods: This study performed linkage disequilibrium score regression (LDSC) and pleiotropic analysis under composite null hypothesis (PLACO) to explore genetic associations, and bidirectional mendelian randomization (MR) to assess the causality between ADHD and thirteen ocular disorders. Results: LDSC showed ADHD genetically correlated with corneal ulcer, keratitis, blepharochalasis, lacrimal system disorders, senile cataract, retinal vascular occlusion, and age-related macular degeneration. MR revealed genetic liability to ADHD increased the risk of corneal ulcer (OR = 1.18, FDR adjusted P = 0.01), keratitis (OR = 1.13, P = 0.007), blepharochalasis (OR = 1.23, P = 0.002), and lacrimal system disorders (OR = 1.09, P = 0.04), while decreasing the risk of primary open-angle glaucoma (OR = 0.83, P = 0.003), exfoliation glaucoma (OR = 0.71, P = 0.001), and normotensive glaucoma (OR = 0.79, P = 0.02). Conversely, genetic liability to strabismus increased ADHD risk (OR = 1.09, P = 0.03). The identification of pleiotropic loci using PLACO suggested that genetic factors played a role in the associations between ADHD and ocular diseases. Conclusions: This study revealed genetic associations between ADHD and multiple ocular disorders, identifying causal effects of ADHD on an increased risk of corneal ulcer, keratitis, blepharochalasis, and lacrimal system disorders, while showing a protective effect against glaucoma. Conversely, genetic liability to strabismus increased ADHD risk.</p>