Genetics of Keratoconus: A Comprehensive Review

Area of Science:

• Ophthalmology
• Genetics
• Corneal Diseases

Background:

• Keratoconus (KC) is a progressive, multifactorial corneal ectatic disorder.
• It is characterized by stromal thinning and irregular astigmatism, with variable incidence and prevalence.
• Genetic predisposition, family history, and syndromic associations are significant risk factors.

Purpose of the Study:

• To review and synthesize current evidence on genes implicated in KC pathogenesis.
• To integrate confirmed pathogenic variants, associations, and negative findings across diverse populations.
• To outline priorities for future research in KC diagnosis, risk stratification, and therapeutic development.

Main Methods:

• Review of candidate gene investigations.
• Analysis of modern genomic approaches, including genome-wide association studies (GWAS), linkage analyses, and next-generation sequencing.
• Synthesis of findings from ethnically diverse cohorts.

Main Results:

• Numerous genes involved in ECM assembly, collagen synthesis, oxidative stress, and transcriptional regulation have been investigated.
• GWAS and sequencing have identified multiple loci and variants potentially involved in KC.
• Some genes show population-specific associations, underscoring genetic variability.

Conclusions:

• The genetic architecture of KC is complex, with both shared and population-specific factors.
• Understanding this genetic variability is essential for improving KC diagnosis and treatment.
• Future research requires ethnically diverse cohorts to fully elucidate KC pathogenesis.