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American Journal of Epidemiology 2005 161(8):707-713; doi:10.1093/aje/kwi102
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved

ORIGINAL CONTRIBUTIONS

Polygenic Effects and Cigarette Smoking Account for a Portion of the Familial Aggregation of Nuclear Sclerosis

Alison P. Klein1, Priya Duggal1, Kristine E. Lee2, Jennifer A. O'Neill1, Ronald Klein2, Joan E. Bailey-Wilson1 and Barbara E. K. Klein2

1 Statistical Genetics Section, Inherited Disease Research Branch, National Human Genome Research Institute, Baltimore, MD
2 Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI

Correspondence to Dr. Barbara E. K. Klein, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Ocular Epidemiology, 610 North Walnut Street, Room 409, Madison, WI 53726 (e-mail: kleinb{at}epi.ophth.wisc.edu).

Cataract is the most common cause of blindness worldwide. Nuclear cataract, an advanced stage of nuclear sclerosis, is the most common type of age-related cataract. The authors assessed data from 2,089 persons within 620 extended pedigrees who participated in the 1988–1990 Beaver Dam Eye Study in Wisconsin to determine whether the observed familial aggregation of nuclear sclerosis could be explained by inheritance of a major gene. Familial correlations were examined and segregation analyses were performed on nuclear sclerosis measurements adjusted for age, sex, and pack-years of cigarette smoking. There was modest correlation among close family members after adjustment for age, sex, and pack-years of cigarette smoking: 0.084 between parents and offspring, and 0.198 between sibling pairs. Although results do not support involvement of a single major locus in the etiology of nuclear sclerosis, models that allowed for familial correlation, attributable in part to polygenic effects, did provide a better fit to the observed data than models without a polygenic effect. This finding suggests that several genes of modest effect may influence development of nuclear lens opacity, possibly in conjunction with environmental factors. Cigarette smoking was an important covariate in these analyses. Overall, results highlight the complex etiology of nuclear sclerosis.

cataract; eye diseases; family; genes; genetic predisposition to disease; heredity; smoking

Abbreviations: SD, standard deviation


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