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Background <p>Keratoconus is a complex disease of the cornea, in part caused by environmental exposures whose nature is not fully understood.</p> Methods <p>This study relied on previously published results from genome-wide association studies of European ancestry. Summary statistics of available genome-wide association studies on atopy, chronic inflammatory disease and serum glucose levels; results were paired with genomic association results for keratoconus into a well-powered and hypothesis-driven Mendelian Randomisation to statistically test the causal role that may have over keratoconus risk.</p> Results <p>Our results confirm a higher risk of keratoconus in patients having any atopic disease (OR = 1.84, 95%CI = 1.52–2.22), but also other chronic inflammatory conditions such as rheumatoid arthritis (OR<sub>IVW</sub> = 1.11, 95%CI = 1.04–1.18) and Crohn’s Disease (OR<sub>IVW</sub> = 1.08, 95%CI = 1.02–1.15). Also, higher glucose levels considerably reduced keratoconus risk (OR<sub>IVW</sub> = 0.49, 95% CI = 0.33–0.72)</p> Conclusions <p>Our results suggest that, in addition to atopy, exposure to specific types of systemic inflammatory responses that develop into chronic conditions may increase keratoconus risk. These results will help clinicians to better evaluate the overall keratoconus risk, disease severity and potentially its progression. In conjunction with individual genetic risk profiles, the presence of exposure to atopic disease, high eosinophil counts and comorbidities could have an important predictive role.</p>

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Influence of inflammatory and metabolic factors on keratoconus risk: a causal inference analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月19日

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  • Pirro G. Hysi,
  • Alison J. Hardcastle,
  • Alice E. Davidson,
  • Loretta Szczotka-Flynn,
  • Anthony P. Khawaja,
  • Petra Liskova,
  • Sudha Iyengar,
  • Chris J. Hammond,
  • Stephen J. Tuft

摘要

Background

Keratoconus is a complex disease of the cornea, in part caused by environmental exposures whose nature is not fully understood.

Methods

This study relied on previously published results from genome-wide association studies of European ancestry. Summary statistics of available genome-wide association studies on atopy, chronic inflammatory disease and serum glucose levels; results were paired with genomic association results for keratoconus into a well-powered and hypothesis-driven Mendelian Randomisation to statistically test the causal role that may have over keratoconus risk.

Results

Our results confirm a higher risk of keratoconus in patients having any atopic disease (OR = 1.84, 95%CI = 1.52–2.22), but also other chronic inflammatory conditions such as rheumatoid arthritis (ORIVW = 1.11, 95%CI = 1.04–1.18) and Crohn’s Disease (ORIVW = 1.08, 95%CI = 1.02–1.15). Also, higher glucose levels considerably reduced keratoconus risk (ORIVW = 0.49, 95% CI = 0.33–0.72)

Conclusions

Our results suggest that, in addition to atopy, exposure to specific types of systemic inflammatory responses that develop into chronic conditions may increase keratoconus risk. These results will help clinicians to better evaluate the overall keratoconus risk, disease severity and potentially its progression. In conjunction with individual genetic risk profiles, the presence of exposure to atopic disease, high eosinophil counts and comorbidities could have an important predictive role.