Shared Genetic Architecture Between Psychiatric Disorders and Keratoconus: Insights From a Large-Scale Genome-Wide...

Area of Science:

• Genetics
• Ophthalmology
• Psychiatry

Background:

• Previous reports suggest a correlation between keratoconus (KC) and psychiatric disorders.
• However, the underlying genetic basis for this association remains largely unexplored.

Purpose of the Study:

• To investigate the genetic overlaps and potential causal relationships between keratoconus and six major psychiatric disorders.
• To identify shared genetic loci and genes contributing to both conditions.

Main Methods:

• Utilized genome-wide association study summary data for cross-trait pleiotropic analysis.
• Performed functional annotations, tissue-specific investigations, and bidirectional Mendelian randomization.
• Applied multiplicity testing to identify significant pleiotropic single nucleotide variants and loci.

Main Results:

• Identified significant genetic correlations and overlaps between KC and three psychiatric disorders.
• Discovered 13 pleiotropic genetic loci, with 3 confirmed as colocalized, and 137 pleiotropic genes.
• Found enrichment of these genes in brain and fibroblasts, implicating the Wnt/β-catenin signaling pathway.

Conclusions:

• Provides evidence for a complex genetic relationship between KC and attention-deficit/hyperactivity disorder, anorexia nervosa, and posttraumatic stress disorder.
• Suggests potential for developing novel therapeutic strategies and improving clinical management for patients with these comorbidities.