Genetic epidemiology in age‐related cataract research

Abstract

Abstract Purpose Age‐related cataracts are the major cause of blindness worldwide. However, the contribution of genetics to their etiology is largely unknown. In contrast, the congenital and juvenile forms of cataracts are mainly caused by de‐novo or hereditary mutations leading to severe changes in the structure and/or function of the corresponding proteins – as it is obvious from the dominant mode of inheritance of most of the mutations. In addition to rare mutations, these cataract‐causing genes have also polymorphic sites in their regulatory and coding sequences (single nucleotide polymorphisms, SNPs); they might contribute to minor changes in the structure and/or function of the corresponding proteins. These alterations could be cataractogenic per se (in a mild form) or they might lead to an increased sensitivity of the proteins to environmental stress. Methods In a new population‐based study in Augsburg (Germany), which will be finished in summer 2008, ~3000 probands have been asked for cataracts; the answers are being validated and further specified by the treating ophthalmologists. Results 16 SNPs from known cataract causing genes (coding for crystallins, connexins and transcription factors) have been identified to be informative without violation of the Hardy‐Weinberg equilibrium. They will be tested with respect to their association with age‐related cataracts by logistic regression allowing for adjustment with respect to age, gender and other confounding effects. Conclusion The results will be presented and discussed.