Genetic Epidemiological Analysis of the Keratoconus Genetic Model in the Chinese Keratoconus Cohort Study

Keratoconus (KC) is a corneal disorder characterized by progressive corneal protrusion and thinning. Our previous studies have demonstrated that genetic factors influence KC occurrence. The purpose of this study was to explore the genetic model of KC from the perspective of genetic epidemiology.

A total of 157 KC families, including 157 KC probands and their 445 first-degree relatives, from the Chinese Keratoconus (CKC) Cohort Study were included in present study. The genetic model of KC was evaluated by three genetic epidemiological analyses, including the Penrose method, simple segregation analysis, and complex segregation analysis, where the complex segregation analysis was conducted using the Statistical Analysis for Genetic Epidemiology package.

The 157 KC families included 181 affected individuals, 384 unaffected individuals, and 37 unknown individuals. There are 24 individuals diagnosed with KC among the 445 first-degree relatives. The relative frequency calculated by the Penrose method was 33.188, which was close to 1/√q. In addition, the segregation ratio calculated by the simple segregation analysis was 0.046, which was less than 1/4. Furthermore, all the hypotheses of Mendelian, nontransmission and environmental model were rejected by complex segregation analysis. These results fully showed that KC is a disease of multifactorial inheritance.

This study identified that KC followed a pattern of multifactorial inheritance, which is helpful to provide initial guidance for prevention and management of the disease and points out a research direction for future research.