Biomedical subjects

Mohamed Dirani

Publications and source records attributed to Mohamed Dirani.

8 recordsLinked to original sources

PubMed2007

Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study.

To examine the familial correlations, heritability (h(2)) and common environmental components (c(2)) of myopia and ocular biometric traits (all treated as continuous outcomes) in families collected through the Genes in Myopia (GEM) family study in Australia. A total of 132 pedigrees (723 participants) were recruited for this study. All individuals completed a risk factor questionnaire and underwent a detailed eye examination including spherical equivalent (SphE) and ocular biometric measurements of axial length (AL), anterior chamber depth (ACD) and corneal curvature (CC). Familial correlations were calculated and h(2) and c(2) were estimated using a variance component model that assumes a multivariate t distribution within each pedigree. Two definitions of common environments (c(2)) were considered: nuclear family (current) shared environment (Model 1) and sib-ship (childhood) shared environment (Model 2). Population ascertainment adjustment was performed using the Blue Mountains eye study dataset. The trends observed for familial correlations suggested that SphE is influenced by both environmental and genetic factors whereas AL, ACD and CC are predominantly genetically determined. This was largely confirmed by variance components modelling. Heritability estimates (adjusted for age, sex and years of education) from the best fitting ACE model (Model 2, childhood shared environment) were 0.50 +/- 0.05 for SphE, 0.73 +/- 0.04 for AL, 0.78 +/- 0.04 for ACD and 0.16 +/- 0.06 for CC. Childhood environmental effects were significant with c(2) estimated to be 0.33 +/- 0.04 for SphE, 0.06 +/- 0.03 for AL, 0.22 +/- 0.04 for ACD and 0.10 +/- 0.05 for CC. Age was associated with SphE, total years of education was associated with AL and sex was associated with all traits studied. We used a novel and conservative approach to account for and estimate common environmental effects by specifying either nuclear family or sib-ship environment when estimating heritability estimates and showed that all traits examined (SphE, AL, ACD and CC) are heritable, thus reflecting a genetic component. These traits therefore all represent candidates for quantitative trait linkage analyses.

Adult↗

PubMed2006

Concordant bilateral Duane's Retraction Syndrome (type 1) in female monozygotic twins.

We report a single case study of concordant bilateral Duane's Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.

Diseases in Twins↗

PubMed2006

Heritability of macular thickness determined by optical coherence tomography.

PURPOSE: To examine whether genetic factors significantly influence macular thickness in healthy older subjects. METHODS: A classic twin study was performed to compare the correlation of macular thickness between monozygotic (MZ) and dizygotic (DZ) twins in a sample of population-based volunteer twins. The study included 109 white twin pairs from 50 to 80 years of age without evidence of manifest eye disease and corrected visual acuity better than 6/7.5. Dilated macular optical coherence tomography (OCT), fundus photography, clinical examination, ocular biometry, a health-dietary questionnaire, and subjective autorefraction were performed on all subjects. RESULTS: Correlation of retinal thickness was significantly greater between MZ twin pairs than DZ pairs in all macular regions. The MZ-to-DZ correlation was 0.88:0.44 for the foveal region, 0.79:0.47 for the inner macular region, and 0.81:0.50 for the outer macular region. With adjustment for significant covariates and model fitting, final heritability estimates of 85%, 81%, and 81%, respectively, were obtained. A significant correlation between foveal thickness and gender was present, with the men having significantly thicker foveae. There was a significant negative correlation between outer macular thickness and axial length. CONCLUSIONS: This study confirms that macular thickness in older healthy subjects, as measured by OCT, may be affected by genetic factors. Factors such as axial length, gender and age, warrant further examination in larger population-based studies, as variables that may influence macular thickness. This finding suggests an inherited basis of macular thickness and may help in the understanding of the factors that govern macular structure and function.

Aged↗

PubMed2006

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study.

PURPOSE: A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. METHODS: A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. RESULTS: Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. CONCLUSIONS: Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.

Adolescent↗

PubMed2006

Refractive errors in twin studies.

It is estimated that 1.6 billion people worldwide have myopia, a refractive error, and this number is expected to increase to approximately 2.5 billion by the year 2020. It is now well established that both the environment and genetics play a role in the development of myopia. However, the exact contribution of each of these components to myopia development has yet to be completely determined. Twin studies (classical twin model) are commonly used to determine the weighting of genetic and environmental components in disease. Over the last century, twin studies have investigated the heritability of refractive errors in different sample populations and have collectively supported a genetic basis to refractive errors. However, different sample populations and methods of data collection have produced a wide range of heritability estimates ranging from .5 to .9. This article will review those twin studies that have investigated refractive error, particularly myopia, as well as biometric measures linked to refractive error, to compare heritability estimates and methodology designs.

Diseases in Twins↗

PubMed2005

Methodology and recruitment of probands and their families for the Genes in Myopia (GEM) Study.

PURPOSE: Myopia is considered to be a complex disease involving both environmental and genetic factors. The Genes in Myopia (GEM) Study aims to recruit probands with myopia and their family members to allow genetic analysis of myopia to be undertaken. The purpose of this paper is to describe the methodology and recruitment of probands and families for the GEM Study. METHODS: In a sample-based prospective study, 2,095 probands with myopia of -0.50 DS or worse and a positive family history of myopia were contacted via the Melbourne Excimer Laser Group (MELG) database. Probands and family members recruited into the study undertook a detailed assessment including questionnaire, best-corrected visual acuity, objective and subjective refraction, axial length, anterior chamber depth, keratometry readings, slit-lamp examination, height, weight and head circumference measurements, and blood sample collection for DNA analysis. RESULTS: 280 probands with myopia have been recruited into the GEM Study. Probands had a mean age of 49.33 yrs. (SD +/- 11.64) with the average age of myopia onset being 12.58 years (SD +/- 6.71). The average spherical-component refractive error was: right eye -5.13 DS (SD +/- 3.06) and left eye -5.14 DS (SD +/- 3.16). Probands with extreme myopia (-10 DS or worse) showed the highest study participation rate of 56%, when compared to high (-5 DS < -10 DS) (20%), moderate (-3 DS < - 5 DS) (18%) and low myopia (-0.5 DS < -3 DS) (10%). A total of 279 out of 505 (55%) additional family members recruited were also found to be myopic. CONCLUSIONS: The GEM study has used a targeted approach to identify an Australian cohort with a diverse spread of myopia, ranging from low to extreme. Recruitment of probands via the use of an excimer laser practice has proved to be an efficient and economic means of identifying probands with a family history of myopia. In addition, the participation rate in the study appears to vary reflecting a proband's perception of disease severity.

Adolescent↗

PubMedDate not supplied

Unraveling a complex genetic disease: age-related macular degeneration.

In most of the Western world, age-related macular degeneration (AMD) remains the largest single cause of severe visual impairment, and its prevalence continues to increase. It is considered to be a complex disease, in which multiple genes and environment play a role in pathogenesis. Several environmental insults are implicated with smoking, serum cholesterol, hypertension, sunlight exposure, and many other factors being variously associated with disease pathogenesis. Until recently, there have been relatively few breakthroughs to further our understanding of the genetics of AMD, despite remarkable progress in molecular genetic techniques over the last 20 years, and the fact that many rare inherited macular diseases have had their causative genes mapped. Development of new tools such as high-density single-nucleotide polymorphism chips and microarrays have changed the face of genetic research, but have yet to directly translate into improved clinical outcomes in ophthalmology. However with the recent finding of the Tyr402His polymorphism in the complement factor H gene being implicated in AMD, we are about to witness a new wave of research in this disease. Not only does the identification of a biologically plausible gene identify a new pathway, but it also identifies new biological mechanisms for disease, avenues to pursue treatment, and a better understanding of how the environment interacts with the genetic background to create disease. This article aims to review the process of gene discovery in complex disease, why the search for genes remains difficult, how to translate laboratory findings to a clinical setting, and how these findings will impact on disease treatment and public health issues.

Genetic Variation↗

PubMedDate not supplied

Mirror-image congenital esotropia in monozygotic twins.

Monozygotic twins had mirror-image congenital esotropia and discordant refractive errors. One had right congenital esotropia surgically corrected during childhood, and the other had left congenital esotropia surgically corrected at 3 and 6 years old.

Diseases in Twins↗