Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

Age-related cataract is the leading cause of blindness in the world1 and the leading cause of low vision in the United States,2 where it consumes approximately 60% of the Medicare budget for vision.3 It has been suggested that any intervention that could delay cataract for even 10 years may reduce the number of cataract surgeries in the United States by 45%.4 The potential impact of cataract prevention may be appreciated when we remember that 1 in 20 Americans over the age of 40 years have undergone cataract surgery.2 In the face of current knowledge about cataract and its causes, smoking prevention has been suggested as the most effective prevention strategy.5 Still, the simple clinical observation that some individuals survive very late in life without visually significant lens opacity has recently prompted several investigations into the genetics of age-related cataract as an avenue of research for novel prevention strategies. Available evidence from population-based studies6–9 suggests that cataract does in fact aggregate in families. However, such associations might result either from shared genes or shared environment. Twin studies provide a potentially powerful tool to distinguish between “nature” and “nurture,” and have been consistent with the idea of a genetic influence on age-related cataract.10,11 However, such studies are dependent on assumptions about the shared environment of different types of twins, and such assumptions are inherent in the models used to analyze these data. A practical difficulty in studies of the genetics of cataract, as with all age-related diseases, is that unaffected status at the time of examination may mean that the individual is truly unaffected or that he or she has simply not manifested the phenotype yet. Misattribution can thus be a serious problem in all but the oldest populations. An additional difficulty in performing studies to ascertain the degree of heritability of age-related cataract in the United States is that general access to cataract surgical services leads to systematic censorship of the most affected persons in the population, with attendant loss of power and possible introduction of bias. In the current investigation, we studied the heritability of nuclear cataract in a cohort of older sibships recruited through the Salisbury Eye Examination (SEE) on Maryland's Eastern Shore. We attempted to overcome some of the mentioned difficulties in studying the genetics of age-related cataract. To distinguish between familial aggregation of cataract due to environmental and genetic causes, information was collected on major personal and environmental cataract risk factors, including cigarette, alcohol, exogenous estrogen and other medication use, lifetime ultraviolet-B light exposure, serum antioxidant levels, history of diabetes and other relevant medical conditions, and body mass index (BMI). To minimize misattribution due to as yet unaffected individuals who will eventually manifest the phenotype, we chose to work in an older population, with the minimum age for probands of 72 years. Finally, to reduce the impact of censored data from bilaterally pseudophakic individuals, we relied on previous study photographs and records from operating ophthalmologists to assign cataract grades for individuals without a native lens in either eye at the time of enrollment in the study.