Genetic insights into the epidemiology of cataracts, prevention and alternative treatment

Abstract

Cataract, a leading cause of visual impairment and blindness, remains a significant global health challenge, particularly in the context of an aging population. As the global population continues to age, the burden of cataract on healthcare systems, especially in developing countries, is expected to increase. Cataract involves the clouding of the lens, and surgical extraction remains the sole treatment option. Understanding the genetic mechanisms underlying cataract, identifying preventive measures, and exploring alternative treatments are critical to reducing this burden. This thesis utilised UK Biobank generated genome-wide association study (GWAS), and publicly available GWAS data to investigate the shared genetic mechanisms between cataract subtypes and cataract-associated risk factors. It also assessed alcohol consumption, vitamin D levels and deficiency, and lanosterol as potential modifiable risk factors or alternative treatment options. Genetic correlations were identified between overall cataract and type 2 diabetes (T2D), asthma and diabetic cataract, senile and diabetic cataract, and asthma and overall cataract. Co-localisation analysis highlighted genes of interest, including WWP2 and CDKN2B-AS1 between overall cataract and T2D, and HLA-DQB1 between asthma and overall cataract. Mendelian randomisation analyses found no evidence of a causal relationship between vitamin D levels, vitamin D deficiency, or alcohol consumption and cataract. Similarly, lanosterol was not supported as a viable alternative treatment option. In summary, while this study identified genetic links between cataracts and associated risk factors; it did not provide supporting evidence for vitamin D, alcohol, and lanosterol as effective preventive measures or alternative treatment options.