Genetic and environmental influences on optimism and its relationship to mental and self-rated health: a study of aging twins.

Optimism has been shown to be important in maintaining wellbeing into old age, but little is known about the sources of variation in optimism and its links to mental and somatic health. Optimism, mental, and self-rated health were measured in 3,053 twin individuals (501 MZF, 153 MZM, 274 DZF, 77 DZM, and 242 DZ opposite-sex twin pairs and 561 single twins) over 50 years using the life orientation test, the General Health Questionnaire and a single-item question for self-rated health. Additive genetic factors explained 36, 34, and 46% of the variation in optimism, mental, and self-rated health, respectively, with the remainder being due to non-shared environmental influences. Genetic influences accounted for most of the covariance between the variables (14-20% of the genetic variance) indicating that in older adults genes predisposing to high optimism also predispose to good mental health and self-rated health.

Genetic covariation between theAuthor Recognition Test and reading and verbal abilities: what can we learn from the analysis of high performance?

The Author Recognition Test (ART) measures print exposure and is a unique predictor of phonological and orthographic processes in reading. In a sample of adolescent and young adult twins and siblings (216 MZ/430 DZ pairs, 307 singletons; aged 11-29 years) ART scores were moderately heritable (67%) and correlated with reading and verbal abilities, with genes largely accounting for the covariance. We also examine whether high (and low) (i.e. 1SD above the mean) represents a quantitative extreme of the normal distribution. Heritability for high ART was of similar magnitude to the full sample, but, a specific genetic factor, independent from both low ART performance and high reading ability, accounted for 53-58% of the variance. This suggests a distinct genetic etiology for high ART ability and we speculate that the specific genetic influence is on orthographical processing, a critical factor in developing word recognition skills.

A population-based study of Australian twins with melanoma suggests a strong genetic contribution to liability.

Melanoma runs within families, but this may be due to either shared genetic or shared environmental influences within those families. The concordance between pairs of non-identical twins compared to that between identical twins can be used to determine whether familial aggregation is due to genetic or environmental factors. Mandatory reporting of melanoma cases in the state of Queensland yielded approximately 12,000 cases between 1982 and 1990. Twins in this study and from the adjacent state of New South Wales (125 pairs in total) were used to partition variation in liability to melanoma into genetic and environmental factors. Identical twins were more concordant for melanoma (4 of 27 pairs) than non-identical twins (3 of 98 pairs; P-value approximately 0.04). Identical co-twins of affected individuals were 9.8 times more likely to be affected than by chance. However, non-identical co-twins of affected individuals were only 1.8 times more likely to be affected than by chance. An MZ:DZ recurrence risk ratio of 5.6 suggests that some of the genetic influences on melanoma are due to epistatic (gene-gene) interactions. Using these data and population prevalences, it was estimated that 55% of the variation in liability to melanoma is due to genetic influences.

Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2.

Genetic studies of pigmentation have benefited from spectrophotometric measures of light-dark hair color. Here we use one of those measures, absorbance at 650 nm, to look for chromosomal regions that harbor genes affecting hair pigmentation. At 7p15.1, marker D7S1808 was suggestive of linkage to light-dark hair color (LOD approximately 2.99). Marker D1S235 at 1q42.3 was suggestive of linkage to hair color (light-dark or blonde-black continuum) (LOD approximately 2.14). However, the most consistent linkage peak was over the gene oculocutaneous albinism type II (OCA2) on chromosome 15. Linkage analysis of both spectrophotometrically quantified and ordered ratings of hair color had LOD scores about 1.2, significant because of the almost perfect concordance. A quantitative transmission disequilibrium test between light-dark hair color and 58 single nucleotide polymorphisms in OCA2 showed that the SNPs rs4778138 (also called rs11855019) and rs1375164 were associated with significantly darker hair color (P approximately 3 x 10(-4) and P approximately 0.03 after correction for multiple testing, respectively). These two SNPs explain 1.54 and 0.85% of variation in the A650t index, respectively.

Evidence of shared genes in refraction and axial length: the Genes in Myopia (GEM) twin study.

PURPOSE: Axial length has been shown to explain up to 50% of the total variance in refraction, with axial length and refraction having a major genetic component. However, no study has attempted to determine whether the correlation between axial length and refraction is explained by shared genetic or environmental factors. METHODS: All twins from Victoria aged 18 years or older were invited to participate in the Genes in Myopia (GEM) twin study through the Australian Twin Registry (ATR). Each twin completed a general questionnaire and underwent dilated objective refraction assessment and measurement of axial length. RESULTS: A total of 612 twin pairs (1224 twins) aged from 18 to 86 years were examined in the GEM twin study. Axial length correlated negatively with refraction (r = -0.64 in the men, r = -0.68 in the women; P < 0.01). The sex limitation ADE (A, additive genetic; D, dominant genetic; E, unique environmental factors) model provided the best-fit genetic model for both measures. Of the variation in spherical equivalence in both the men and the women, approximately 50% were due to genetic factors influencing axial length. CONCLUSIONS: From these findings, it is likely that axial length and refraction share common genes in their etiology. The GEM twin study has provided a basis and direction for future research into identifying the gene(s) in axial length that will ultimately improve our understanding of the etiology of refractive error, particularly myopia.

Red hair is the null phenotype of MC1R.

The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

Dominant genetic effects on corneal astigmatism: the genes in myopia (GEM) twin study.

PURPOSE: This study was conducted to assess the relative influence of genetics and environment on corneal astigmatism and corneal curvature in a large sample of twins. METHODS: A total of 612 twin pairs (345 monozygotic [MZ] and 267 dizygotic [DZ]) aged between 18 and 86 years (mean age, 52.11 +/- 15.85 years) were recruited from the Australian Twin Registry (ATR). Each subject completed a general questionnaire, undertook a dilated eye examination, including ocular biometric measurements, and contributed a blood sample. Corneal astigmatism was defined as the absolute difference between the K1 and K2 meridians and corneal curvature as the average of K1 and K2. RESULTS: Intrapair correlations were significantly higher (P < 0.001) in MZ twin pairs compared with those in DZ twin pairs for both corneal astigmatism (CA; rmz = 0.48 vs. rdz = 0.13) and corneal curvature (CC; rmz = 0.84 vs. rdz = 0.41). A sex-limited model with parameters estimating additive genetic, nonadditive genetic, and unique environmental influences (denoted ADE) was the most parsimonious model explaining both measures. Heritability estimates were as high as 60% and 71% for CA and CC, respectively. CONCLUSIONS: This study provides evidence that genetic factors explain interindividual variation in CA and CC, with nonadditive genetic factors explaining most of the variance due to those genetic factors. Heritability estimates were sex specific and indicate the need for future linkage studies for the identification of genes involved in the etiology of CA and CC.

Adult-onset myopia: the Genes in Myopia (GEM) twin study.

PURPOSE: To report the frequency of adult-onset myopia in a large cohort of Caucasian twins that were assessed as part of the Genes in Myopia (GEM) twin study and to quantify the genetic contribution in adult-onset myopia using the classic twin model. METHODS: All twins aged 18 years or older were invited to participate in the GEM twin study through the Australian Twin Registry (ATR). Each twin completed a standard questionnaire and underwent a comprehensive eye assessment, including cycloplegic objective examination. Adult-onset myopia was defined as having the first spectacle/contact lens correction at the age of 18 years or older. Myopia was defined as spherical equivalent worse than or equal to -0.50 D. RESULTS: A total of 1224 twins (690 monozygotic [MZ] and 534 dizygotic [DZ]) between 18 and 86 years of age were recruited into the GEM study. A total of 96 twins (96/347 = 27.7%) comprising 50 MZ and 46 DZ twins were first prescribed optical correction for myopia at the age of 18 years or older. A significantly higher MZ intrapair correlation (r = 0.61) compared with that in DZ twins (r = 0.16, P < 0.01) for spherical equivalent was found in twins with adult-onset myopia. CONCLUSIONS: Adult-onset myopia is a relatively common condition, with approximately one quarter of cases occurring in adulthood. To the authors' knowledge, the GEM twin study is the first study of its kind to provide evidence to support a genetic component in adult-onset myopia.

Spectrophotometric methods for quantifying pigmentation in human hair-influence of MC1R genotype and environment.

Eumelanin (brown/black melanin) and pheomelanin (red/yellow melanin) in human hair can be quantified using chemical methods or approximated using spectrophotometric methods. Chemical methods consume greater resources, making them less attractive for epidemiological studies. This investigation sought to identify the spectrophotometric measures that best explain the light-dark continuum of hair color and the measure that is best able to distinguish red hair from nonred hair. Genetic analysis was performed on these two measures to determine the proportion of genetic and environmental influences on variation in these traits. Reflectance curves along the visible spectrum and subjective ratings of hair color were collected from 1730 adolescent twin individuals. Discriminant class analyses were performed to determine the spectrophotometric measure that could best proxy for eumelanin and pheomelanin quantities. The ratio of light reflected in the green portion of the spectrum to that reflected in the red portion of the spectrum was best able to distinguish red hair from nonred hair. Melanocortin 1 receptor (MC1R) genotype explained some, but not all, variation in this measure. Light absorbed in the red portion of the spectrum was best able to explain the light-dark continuum of hair color. Variance components analysis showed that there were qualitatively different genetic influences between males and females for the light-dark continuum of hair. Our results show that spectrophotometric measures approximating variation in eumelanin and pheomelanin may be considered as an alternative to chemical methods in larger epidemiological studies.

Genetic and environmental influences on individual differences in attitudes toward homosexuality: an Australian twin study.

Previous research has shown that many heterosexuals hold negative attitudes toward homosexuals and homosexuality (homophobia). Although a great deal of research has focused on the profile of homophobic individuals, this research provides little theoretical insight into the aetiology of homophobia. To examine genetic and environmental influences on variation in attitudes toward homophobia, we analysed data from 4,688 twins who completed a questionnaire concerning sexual behaviour and attitudes, including attitudes toward homosexuality. Results show that, in accordance with literature, males have significantly more negative attitudes toward homosexuality than females and non-heterosexuals are less homophobic than heterosexuals. In contrast with some earlier findings, age had no significant effect on the homophobia scores in this study. Genetic modelling showed that variation in homophobia scores could be explained by additive genetic (36%), shared environmental (18%) and unique environmental factors (46%). However, corrections based on previous findings show that the shared environmental estimate may be almost entirely accounted for as extra additive genetic variance arising from assortative mating for homophobic attitudes. The results suggest that variation in attitudes toward homosexuality is substantially inherited, and that social environmental influences are relatively minor.

The role of educational attainment in refraction: the Genes in Myopia (GEM) twin study.

PURPOSE: Educational attainment has been proposed as one of the most consistent environmental risk factors associated with myopia. The Genes in Myopia (GEM) twin study is the first myopia twin study to determine the relative genetic contribution in educational attainment as well as assessing the shared genetic and environmental factors between educational attainment and refraction through structural equation modeling. METHODS: All twins from Victoria aged 18 years or older were invited to participate in this study through the Australian Twin Registry (ATR). Each twin completed a general questionnaire, and a comprehensive eye examination was undertaken. Education level was categorized to provide a level of attainment. RESULTS: A total of 612 twin pairs with a mean age of 52.36 years were examined. Higher educational attainment was significantly associated with a more myopic refraction (r = -0.21, P < 0.01), with educational attainment explaining 4.41% of the total variance in refraction. Findings from the GEM twin study found that genes (additive genetic effects) explained 69% of the variance in educational attainment and common and unique environmental factors accounted for 20% and 11% of the variance, respectively. Of the genetic influences on refraction, 3.2% were common with those influencing educational attainment. CONCLUSIONS: The GEM twin study has shown that educational attainment is strongly influenced by genes, and therefore this risk factor should not solely be considered as an environmental risk factor. The same genetic factors that influence an individual's educational attainment may also be involved in the development of refractive error.

Receptor function, dominant negative activity and phenotype correlations for MC1R variant alleles.

The human melanocortin-1 receptor (MC1R) is a G-protein coupled receptor involved in the regulation of pigmentation. Several MC1R variant alleles are associated with red hair, fair skin and increased skin cancer risk. We have performed a systematic functional analysis of nine common MC1R variants and correlated these results with the strength of the genetic association of each variant allele with pigmentation phenotypes. In vitro expression studies revealed that variant receptors with reduced cell surface expression, including V60L, D84E, R151C, I155T, R160W and R163Q, showed a corresponding impairment in cAMP coupling. The R142H and D294H variants demonstrated normal cell surface expression, but had reduced functional responses, indicating that altered G-protein coupling may be responsible for this loss of function. The V92M variant cAMP activation was equal to or higher than that for wild-type MC1R. In co-expression studies, the D84E, R151C, I155T and R160W variants showed a dominant negative effect on wild-type receptor cell surface expression, which was reflected in a decreased ability to elevate intracellular cAMP levels. The D294H variant also demonstrated a dominant negative effect on wild-type MC1R cAMP signalling, but had no effect on wild-type surface expression. Importantly, comparison of the in vitro receptor characteristics with skin and hair colour data of individuals both homozygous and heterozygous for MC1R variant alleles revealed parallels between variant MC1R cell surface expression, functional ability, dominant negative activity and their effects on human pigmentation. These findings show the first direct correlations between variant MC1R biochemical properties and pigmentation phenotype.

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.