Elsevier

Survey of Ophthalmology

Volume 55, Issue 6, November–December 2010, Pages 561-583
Survey of Ophthalmology

Genetics in Ophthalmology
The Heritability of Ocular Traits

https://doi.org/10.1016/j.survophthal.2010.07.003Get rights and content

Abstract

Heritability is the proportion of phenotypic variation in a population that is attributable to genetic variation among individuals. Many ophthalmic disorders and biometric traits are known to have a genetic basis and consequently much work has been published in the literature estimating the heritability of various ocular parameters. We collated and summarized the findings of heritability studies conducted in the field of ophthalmology. We grouped the various studies broadly by phenotype as follows: refraction, primary open-angle glaucoma, age-related macular degeneration (AMD), cataract, diabetic retinopathy, and others. A total of 82 articles were retrieved from the literature relating to estimation of heritability for an ocular disease or biometric trait; of these, 37 papers were concerned with glaucoma, 28 with refraction, 4 with AMD, 5 with diabetic retinopathy, and 4 with cataract. The highest reported heritability for an ophthalmic trait is 0.99 for the phenotype ≥ 20 small hard drusen, indicating that observed variation in this parameter is largely governed by genetic factors. Over 60% of the studies employed a twin study design and a similar percentage utilized variance components methods and structural equation modeling (SEM) to derive their heritability values. Using modern SEM techniques, heritability estimates derived from twin subjects were generally higher than those from family data. Many of the estimates are in the moderate to high range, but to date the majority of genetic variants accounting for these findings have not been uncovered, hence much work remains to be undertaken to elucidate fully their molecular etiology.

Section snippets

Demystifying Heritability

The origin of the term heritability remains unknown, although it appears to have been in use since the early 19th century. Its initial connotation was a broad one of inheritance as related to the genetic transmission of biological characteristics. A full century passed before its meaning or definition converged to that in the current lexicon, and Lush is credited with its origin in this sense.14

In addition to human populations, the concepts underlying heritability were of paramount importance

Dissecting complex disease

Modern genetics has made the greatest inroads in medicine by elucidating the genetic mechanisms responsible for the rare single-gene, or “Mendelian”, diseases with known modes of inheritance. The genetic nature of numerous ophthalmic conditions of this kind (e.g., retinitis pigmentosa) have been described in the literature.96 The more common human diseases tend to be more complex in that they result from the interplay of multiple genes interacting with various environmental factors. This

Summary

Approximately 80 individual studies investigating the heritability of various ophthalmic traits were retrieved from the literature. Thirty-seven were concerned with POAG, 28 papers with refraction, 4 with AMD, 5 with diabetic retinopathy, and 5 with cataract. The highest reported heritability for an ophthalmic trait is 0.99 for the phenotype ≥ 20 small hard drusen, indicating that observed variation in this parameter is largely governed by genetic factors. Conversely, corneal fluorescence has

Method of Literature Search

A systematic search on Medline, ISI Web of Science, Scopus, and Google Scholar was conducted initially using the following (combinations of) keywords: heritability, twins, twin study, family study, familial aggregation, pedigree, eye, ocular, ophthalmic. No date or language limitations were applied to the search. From the list of abstracts identified, original investigations and review articles were included and the bibliography of the retrieved articles examined for additional relevant

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    Publication of this article was financially supported by the Ophthalmic Research Institute of Australia and the Australian National Health and Medical Research Council. The Centre for Eye Research Australia (CERA ) receives Operational Infrastructure support from the Victorian Government. D.A.M. is a Pfizer Australia research fellow. C.J.H. is funded by the UK National Institute for Health Research. P.G.S. is the recipient of an NHMRC postgraduate scholarship. P.G.S., A.W.H., C.J.H., and D.A.M. are authors of studies included in this review. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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