A Shared Genetic Basis Underlying Myopia-Exotropia Comorbidity

Area of Science:

• Ophthalmology
• Genetics
• Complex Trait Genetics

Background:

• Myopia and exotropia frequently co-occur, suggesting a potential shared underlying etiology.
• Understanding the genetic basis of this comorbidity is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the shared genetic architecture between myopia and exotropia.
• To identify genetic variants and pathways contributing to the comorbidity of these two eye conditions.

Main Methods:

• Utilized large-scale genome-wide association study (GWAS) data to analyze genetic correlation and polygenic overlap.
• Employed multi-trait analysis of GWAS (MTAG) for cross-trait meta-analysis and prioritized shared genetic signals.
• Conducted colocalization, fine mapping, local genetic correlation, and in silico transcriptomic/regulatory analyses.

Main Results:

• A significant positive genetic correlation (rg = 0.25; P = 0.044) was observed between myopia and exotropia.
• Identified substantial polygenic overlap with 201 shared non-null variants, predominantly with concordant effect directions.
• The TSPAN10 locus (rs7405453) emerged as a strong shared signal, though not the sole driver of the genetic correlation.

Conclusions:

• The comorbidity of myopia and exotropia is partly explained by shared genetic factors.
• Further research with larger cohorts, refined phenotyping, and functional studies is necessary to elucidate the precise mechanisms.