Gene-environment interactions and aging visual function: a classical twin study.

OBJECTIVE:
To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging.
DESIGN:
A classical twin study.
PARTICIPANTS:
Forty-two twin pairs (21 monozygotic and 21 dizygotic; age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry.
METHODS:
Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap resampling was used to return robust intrapair correlations for each parameter.
MAIN OUTCOME MEASURES:
Psychophysical thresholds and adaptational time constants.
RESULTS:
The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83; P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime.
CONCLUSIONS:
Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention.

Heritability of the spatial distribution and peak density of macular pigment:a classical twin study

Purpose: To elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study.

Methods: Fundus autofluorescence images were obtained at 488?nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2±5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0-255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis.

Results: A significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI -0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI -0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977).ConclusionsrPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters. © 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12

Heritability of peripheral refraction in Chinese children and adolescents: the Guangzhou Twin Eye study.

PURPOSE:

To estimate the heritability of peripheral refraction in Chinese children and adolescents.

METHODS:

The authors examined 72 monozygotic (MZ) twins and 48 dizygotic (DZ) twins aged 8 to 20 years from a population-based twin registry. Temporal and nasal peripheral refraction, each 40° from the visual axis, and axial refraction were measured using an autorefractor. Relative peripheral refractive error (RPRE) was defined as the peripheral refraction minus the axial refraction. Heritability was assessed by structural equation modeling after adjustment for age and sex.

RESULTS:

The mean and SD of temporal refraction (T(40)), nasal refraction (N(40)), RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were -0.27 ± 2.0 D, 0.36 ± 2.19 D, 1.18 ± 1.39 D, 1.80 ± 1.69 D, and -0.62 ± 1.58 D, respectively. The intraclass correlations for T(40) refraction, N(40) refraction, RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were 0.87, 0.83, 0.65, 0.74, and 0.58 for MZ pairs and 0.49, 0.42, 0.30, 0.41, and 0.32 for DZ pairs, respectively. A model with additive genetic and unique environmental effects was the most parsimonious, with heritability values estimated as 0.84, 0.76, 0.63, 0.70, and 0.55, respectively, for the peripheral refractive parameters.

CONCLUSIONS:

Additive genetic effects appear to explain most of the variance in peripheral refraction and relative peripheral refraction when adjusting for the effects of axial refraction.

Contribution of genetic and environmental effects on lens thickness: the Guangzhou Twin Eye study.

PURPOSE:

This study investigated the heritability of lens thickness (LT) and relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese children and adolescents in the Guangzhou Twin Eye study.

METHODS:

Twins aged 8 to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and axial length (AL) measurements using the Lenstar were taken for each twin. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling, after adjustment for age and sex with the Mx program.

RESULTS:

Seven hundred sixty-eight twin pairs (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142 (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were 0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5% (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%) of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental effects for rLT.

CONCLUSIONS:

This study confirms that the LT in young healthy subjects may be mainly affected by additive genetic factors. High heritability remains even when the data are corrected for the influence of AL with the use of rLT.

The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

The determination of optimal processing conditions for PLA and PLA/CaCO3 in twin screw extrusion using DoE and multivariate analysis

Biodegradable polymers, such as PLA (Polylactide), come from renewable resources like corn starch and if disposed of correctly, degrade and become harmless to the ecosystem making them attractive alternatives to petroleum based polymers. PLA in particular is used in a variety of applications including medical devices, food packaging and waste disposal packaging. However, the industry faces challenges in melt processing of PLA due to its poor thermal stability which is influenced by processing temperatures and shearing.
Identification and control of suitable processing conditions is extremely challenging, usually relying on trial and error, and often sensitive to batch to batch variations. Off-line assessment in a lab environment can result in high scrap rates, long lead times and lengthy and expensive process development. Scrap rates are typically in the region of 25-30% for medical grade PLA costing between €2000-€5000/kg.
Additives are used to enhance material properties such as mechanical properties and may also have a therapeutic role in the case of bioresorbable medical devices, for example the release of calcium from orthopaedic implants such as fixation screws promotes healing. Additives can also reduce the costs involved as less of the polymer resin is required.
This study investigates the scope for monitoring, modelling and optimising processing conditions for twin screw extrusion of PLA and PLA w/calcium carbonate to achieve desired material properties. A DAQ system has been constructed to gather data from a bespoke measurement die comprising melt temperature; pressure drop along the length of the die; and UV-Vis spectral data which is shown to correlate to filler dispersion. Trials were carried out under a range of processing conditions using a Design of Experiments approach and samples were tested for mechanical properties, degradation rate and the release rate of calcium. Relationships between recorded process data and material characterisation results are explored.