Genetics in OphthalmologyThe Heritability of Ocular Traits
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
References (153)
- et al.
Deleterious mutations in the Zinc–Finger 469 gene cause brittle cornea syndrome
Am J Hum Genet
(2008) - et al.
The genetics of primary open-angle glaucoma: a review
Exp Eye Res
(2009) - et al.
Multipoint quantitative-trait linkage analysis in general pedigrees
Am J Hum Genet
(1998) - et al.
An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group
Surv Ophthalmol
(1995) - et al.
Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS)
Ophthalmology
(2001) - et al.
The heritability of corneal hysteresis and ocular pulse amplitude: a twin study
Ophthalmology
(2008) - et al.
Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population
Ophthalmology
(2005) - et al.
A susceptibility locus for myopia in the normal population is linked to the PAX6 gene region on chromosome 11: a genomewide scan of dizygotic twins
Am J Hum Genet
(2004) - et al.
Genetic influence on early age-related maculopathy: a twin study
Ophthalmology
(2002) - et al.
Association of PAX6 polymorphisms with high myopia in Han Chinese nuclear families
Invest Ophthalmol Vis Sci
(2008)
Correlation of intraocular pressures in pairs of monozygotic and dizygotic twins
Ophthalmology
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
Nat Genet
Anterior chamber depth and primary angle-closure glaucoma. II. A genetic study
Acta Ophthalmologica
Variation and heritability of ocular dimensions. A population study among adult Greenland Eskimos
Acta Ophthalmologica
Corneal thickness. II. Environmental and genetic factors
Acta Ophthalmologica
Heritability of myopic refractive errors in identical and fraternal twins
Graefes Arch Clin Exp Ophthalmol
Heritability of the severity of diabetic retinopathy: the FIND–Eye study
Invest Ophthalmol Vis Sci
Segregation analysis of ocular refraction and myopia
Hum Hered
Predicting human height by Victorian and genomic methods
Eur J Hum Genet
A tutorial on statistical methods for population association studies
Nat Rev Genet
Nearwork and familial resemblances in ocular refraction: a population study in Newfoundland
Clin Genet
Heritability in retrospect
J Hered
Homologous retinoblastoma in identical twins
Trans Am Ophthalmol Soc
The inheritance and development of cup and disc diameters
Acta Ophthalmologica
Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population
Hum Genet
Twinning and ocular pathology, with a report of bilateral macular coloboma in monozygotic twins
Trans Am Ophthalmol Soc
OpenMx: Multipurpose Software for Statistical Modeling
R package version 0.3.3–1264
Heritability of corneal curvature and astigmatism: a videokeratographic child-parent comparison study
Cornea
Repeated measures of intraocular pressure result in higher heritability and greater power in genetic linkage studies
Invest Ophthalmol Vis Sci
Heritability of intraocular pressure: a classical twin study
Br J Ophthalmol
Heritability of macular thickness determined by optical coherence tomography
Invest Ophthalmol Vis Sci
The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness
Invest Ophthalmol Vis Sci
Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study
Hum Genet
Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors
Invest Ophthalmol Vis Sci
Refractive errors in twin studies
Twin Res Hum Genet
Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study
Invest Ophthalmol Vis Sci
Dominant genetic effects on corneal astigmatism: the genes in myopia (GEM) twin study
Invest Ophthalmol Vis Sci
A genetic contribution to intraocular pressure: the Beaver Dam Eye Study
Invest Ophthalmol Vis Sci
Likelihood
Introduction to Quantitative Genetics
Corneal thickness and its heredity in the population in North Finland
Bull Eur Soc Hum Genet
Statistical note on the components of ocular refraction in twins
J Med Genet
The history of twins, as a criterion of the relative powers of nature and nurture
Fraser’s Magazine
Regression towards mediocrity in hereditary stature
Journal of the Anthropological Institute
Selected review on genetic factors in myopia
J Am Optom Assoc
Epidemiology and heritability of astigmatism in Norwegian twins: an analysis of self-reported data
Ophthalmic Epidemiol
Welcome to the genomic era
N Engl J Med
The heritability of age-related cortical cataract: the twin eye study
Invest Ophthalmol Vis Sci
Genes and environment in refractive error: the twin eye study
Invest Ophthalmol Vis Sci
Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins
N Engl J Med
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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.