Evidence for a major gene for cortical cataract.

Kleins Lab // Publications // Jan 01 1995

PubMed ID: 7822150

Author(s): Heiba IM, Elston RC, Klein BE, Klein R. Evidence for a major gene for cortical cataract. Invest Ophthalmol Vis Sci. 1995 Jan;36(1):227-35.

Journal: Investigative Ophthalmology & Visual Science, Volume 36, Issue 1, Jan 1995

PURPOSE To examine the possible presence of a major gene determining susceptibility to cortical cataract.

METHODS The percentage of the lens area involved with cortical opacity, summed over both eyes, was evaluated in 1275 individuals from the Beaver Dam Eye Study. After adjusting for the effects of age and sex, these measures of cortical cataract were subjected to sibling correlational analysis, commingling analysis, and segregation analysis. The Box and Cox power transformation was applied to the data for the commingling and segregation analyses. Using regressive models, four modes of transmission were examined, and under each mode three hypotheses and a general model were fitted by maximum likelihood and compared.

RESULTS Sister-sister and brother-brother correlations of the adjusted measures of cortical cataract are significant and similar; the brother-sister correlation is not significantly different either from these correlations or from zero. Two commingled distributions give the best fit to the data, especially after power transformation. Under each of four modes of transmission, the hypothesis that best fits the data is one in which there are only two distributions (and, hence, dominance under mendelian transmission), the power transformation parameter is fixed at the estimate obtained from commingling analysis, and there is residual sibling correlation. The data thus suggest the existence of a major effect for cortical cataract. Random environmental influences can be rejected as a cause of this major effect. Our analysis indicates the existence of a significant effect of sex on the residual variance. Allowing for this, the data suggest transmission of a single major gene, though this may not be the sole cause of the commingled distributions.

CONCLUSIONS Assuming a common variance for the two sexes, a single major gene can account for 58% of the variability of age- and sex-adjusted measures of cortical cataract. With the variance sex dependent, a major gene can account for 75% and 45% of the total variability among males and females, respectively.