Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs

The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus-specific DNA methylation was larger in old individuals than in young individuals, ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P = 3.7 × 10(-07) ). Similarly, there was more within-MZ-pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10(-06) ) to a 16% increase each decade at LEP (P = 2.0 × 10(-08) ). Still, old MZ pairs with strikingly similar DNA methylation were also observed at these loci. After 10-year follow-up in elderly twins, the variation in DNA methylation showed a similar pattern of change as observed cross-sectionally. The age-related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ twins during aging.     

An exploration of the genetic and environmental etiology of heart rate in infancy and middle childhood.

Heart rate was recorded on 210 MZ and 174 DZ same sex twin pairs participating in the MacArthur Longitudinal Twin Study (MALTS) at age 14, 20, 24, 36 months and 7 years. Heart rate was monitored in the laboratory at all ages. At ages 14 to 36 months, heart rate was monitored prior to a set of cognitive tasks. At age 7 years heart rate was recorded during a mood-eliciting videotaped presentation. At this age only heart rate monitored during neutral portions of the presentation were used. Mean heart rate declines substantially across this age range, but is similar in boys and girls and for MZ and DZ twins at each age. Heart rate is moderately correlated across all time points suggesting that individual differences in heart rate are relatively stable over this age range. Multivariate genetic and environmental models were fitted to the raw data. In general, genetic factors contribute to the stability of individual differences over time. Shared and non-shared environment factors tended to be occasion specific, with non-shared environment contributing substantially to the individual variation at each age. Shared environment and non-shared environment also contributed a modicum to the stability across time. Thus, individual differences in resting heart rate is a relatively stable, heritable trait from infancy to early childhood.     

The Premedical Student: His Progress: A Study of a Cohort of Premedical Students at the University of British Columbia

Since September 1961, a prospective study of premedical and science students has been conducted at the University of British Columbia. On completion of their sophomore year, after a year of changes from one group to another or withdrawal from either group, only 82 students existed in the diminished Premedical cohort while 137 students existed in the augmented Science cohort. These two groups have now become similar demographically, and their academic potential, as indicated by achievement and ability tests, has also become similar in terms of their mean test scores. In academic performance the present Premedical cohort has displayed some superiority over the Science cohort in high school, freshman and sophomore years. The sophomore premedical mean grade was 66.0% compared with 63.7% for the Science cohort. The hypothesis is developed that these findings reflect a difference in motivation, and therefore that perception of ultimate career goals will motivate and affect academic performance of students in their undergraduate years.     

Delay in motor development of twins in Africa: a prospective cohort study.

Twins are prone to developmental delay due to prematurity and low birthweight. However it is unknown if twinning is an independent risk factor for developmental delay. The objective of this study was to compare the attainment of a set of gross motor milestones in a cohort of twins and singletons in The Gambia. Eighty-four pairs of twins and 72 singletons were enrolled at birth and followed up until 18 months of age. The mean age at achieving milestones was higher in twins for each development outcome and the difference between twins and singletons was significant after adjustment for confounders for maintaining head, sitting without support and walking. In twins, we found a highly significant correlation within pairs for most milestones. When monozygotic and dizygotic twins were compared, a significant heritability was observed for crawling, sitting, standing and walking, with over 90% of population variance observed due to genetic factors rather than environmental factors. There was little evidence for a genetic contribution towards very early milestones. In conclusion, our data suggest that twinning is an independent risk factor for developmental delay in early life in The Gambia, and that genetic factors contribute strongly to certain motor development outcomes.     

Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

Objective

The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments.

Materials and Methods

The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18–65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23–64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype.

Results

Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits.

Conclusion

Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples.     

Physiological correlates of multiple-sprint ability and performance in international-standard squash players

From measures on a battery of fitness tests in elite-standard squash players on different tiers of a national performance program, we examined the relationships among test scores and player rank, and fitness factors important for squash-specific multiple-sprint ability. Thirty-one (20 men, 11 women) squash players from the England Squash performance program participated: n = 12 senior; n = 7 transition; n = 12 talented athlete scholarship scheme (TASS) players. In 1 test session and in a fixed order, the players completed a battery of tests to assess countermovement jump height, reactive strength, change-of-direction speed, and multiple-sprint ability on squash-specific tests and endurance fitness. Two-way analysis of variance compared senior, transition, and TASS players by sex on all measures except jump height where only senior and transition players were compared. Effect size (ES) was calculated for all comparisons. Pearson's correlation examined relationships among test scores and multiple-sprint ability. Spearman's ρ investigated relationships among test scores and players' rank in men and women separately. Regardless of sex, seniors outperformed TASS players on all except the endurance test (p < 0.05, ES at least 1.1). Seniors had better multiple-sprint ability than did transition players (p < 0.01, ES = 1.2). Transition outperformed TASS players on the reactive-strength test (p < 0.05, ES = 1.0). Men outperformed women in all tests at all performance program tiers (p < 0.05, ES at least 0.5). In men, rank was related to multiple-sprint ability, fastest-multiple-sprint-test repetition, and change-of-direction speed (ρ = 0.78, 0.86, 0.59, respectively). In women, rank was related to fastest multiple-sprint-test repetition (ρ = 0.65). In men and women, multiple-sprint ability was related to change-of-direction speed (r = 0.9 and 0.84) and fastest-multiple-sprint-test repetition (r = 0.96 for both) and to reactive strength in men (r = -0.71). The results confirm that high-intensity variable-direction exercise capabilities are important for success in elite squash.     

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

Fourier analysis of facial profiles of young twins

Twins studies provide a powerful approach to determining the relative contribution of genetics and environment to observed variation. Such studies assume trait differences in monozygous (MZ) twins are due to environmental factors and those in dizygous (DZ) twins are due to both genetic and environmental factors. This study quantitated facial profiles of twins using Fourier equations, determining their value in profile analysis and the assessment of the genetic contribution to facial shape. Standardized profile slide photographs of 79 pairs of 4-6 year-old twins (37 MZ pairs, 42 DZ pairs) were scanned and x and y coordinates were extracted from each profile using sellion and Camper's plane as references. The coordinates were subjected to Fourier analysis and the normalised vertex projection coefficients were studied. The means of the differences between coefficients for MZ co-twins did not differ significantly from that of DZ co-twins, although the DZ group showed higher mean differences in the higher harmonics. Subjective examination of superimposed reconstructions showed wider variation between DZ co-twins than MZ co-twins. Correct classification of twins by discriminant function analysis using Fourier coefficients was similar for both groups (MZ: 70.3%; DZ: 73.8%). Fourier analysis could quantitate facial profiles of young children and differentiate some details, but was unable to discriminate between genetic and environmental influences, and any possible interactions between these influences, on their overall facial profiles at this developmental stage.     

Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence.

Data from 16-year-old Finnish twin pairs were used to estimate familial effects on religiosity and the modification of those effects by sex and residential region. The sample of 2265 twin boys and 2521 twin girls formed 779 monozygotic and 1614 dizygotic pairs, 785 of the same sex and 829 of opposite sex. We compared religiosity scores of twins living in more rural and traditional northern Finland with those living in the more urban and secular southern region. Girls had higher religiosity scores than did boys, and twins living in northern Finland had higher religiosity scores than those resident in southern Finland. Correlations for monozygotic twins were slightly higher than those for dizygotic twins, and covariance modeling found modest heritability of religiosity [11% (95% CI 0-24) for girls; 22% (95% CI 6-38) for boys], and substantial shared environmental effects [60% (95% CI 49-69) and 45% (95% CI 31-57)] among girls and boys, respectively. The correlation between shared environmental effects in boys and girls was estimated to be 0.84 (95% CI 0.73-0.99). In analyses distinguishing region of residence, girls living in southern Finland were found to have significantly higher unshared environmental effects than girls in northern Finland, while boys living in the urban south appeared to have lower shared environmental effects, and higher additive genetic effects, than boys living in the rural north.     

双生子骨龄、身高及体重的研究

本文对307对同性别双生子的骨龄、身高和体重进行了研究。结果表明,骨龄、身高和体重均受遗传因素影响。遗传因素对不同年龄阶段的影响程度可能是不同的。长时间的不同环境因素对身高和体重的影响较骨龄更大。     

Small for gestational age as a predictor of behavioral and learning problems in twins.

The study examines the effects of being born small for gestational age (SGA) on rates of behavioral problems in twins and siblings, utilising data from the Australian Twin Study of disruptive behavior disorders in twins and their siblings. Participants were 3944 twins and their siblings who were assessed at two intervals three years apart. At the first assessment (1991), they ranged between 4 and 12 years of age. Items assessing Attention Deficit/Hyperactivity Disorder were based on DSM-III-R criteria (Time 1) and DSM-IV criteria (Time 2). Other measures included history of speech and reading therapy, demographic information and obstetric and neonatal history. Results indicated that both male and female twins, who were extremely growth restricted (small for gestational age up to the third percentile-WGA3) showed more inattention, and poorer speech and reading scores. The effects were greater for males. Male twins who were small for gestation age, up to the 10th percentile, were more likely to have a DSM-IV diagnosis of Inattention. Implications of these results included WGA3 male twins being at a "triple disadvantage" for subsequent behavioral and learning problems, in that being male, being a twin and being small for gestational age are all significant factors. Recommendations are made for early intervention for low birthweight male twins. The study is consistent with recent follow-up studies of very-low-birthweight singletons, indicating male disadvantage in cognitive outcome. While there is some genetic component to SGA, it does constitute a potentially major contribution to common environmental effects that must be considered in twin-based genetic analyses.     

Characteristics of a Japanese adult twin database of high school graduates.

This paper profiles a unique cohort of adult Japanese twins. The database contains more than 700 twin pairs, aged 18 to 66 years, who are all graduates of the secondary school attached to the faculty of education of the University of Tokyo. This school was established in 1948, when the study of twins was burgeoning in Japan, and about 10 to 20 pairs of twins have been admitted there every year to participate in studies on twins in education and in related projects. The zygosity of all twins was determined carefully on the basis of various sources. Data from the perinatal period to adulthood were linkable using ID numbers. Follow-up surveys in the field of medical genetics were performed in 1985, 1989 and 1999. For the third survey, which was sent and received exclusively by mail, the distribution and collection process was also assessed in detail. The response rate was around 40%, which statistically was influenced mainly by previous participation and sex. The limitation of this cohort is its selection bias concerning socioeconomic status and its imbalance in favor of monozygotic pairs.     

Development and representativeness of a large population-based cohort of native Californian twins.

We have established a large cohort of twins to facilitate studies of the role of genetics and environment in the development of disease. The cohort has been derived from all multiple births occurring in California between 1908-82 (256,616 in total). We report here on our efforts to contact these twins and their completion of a detailed 16 page risk factor questionnaire. Addresses of the individuals were obtained by linking the birth records with the California Department of Motor Vehicles (DMV) roster of licensees. To date this has been completed for twins born between 1908 and 1972 (200,589 individuals). The linkage has revealed 112,468 matches and, because of less complete DMV records in some years, was less successful in older females than in younger females and all males. Over 41,000 twins have participated by completing the questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, we estimate our crude response rate to be between 42.2% and 49.6%, highest among females in their 40s (62.8%). We describe the representativeness of the twins in the original birth cohort, those identified by the linkage, and those completing the questionnaire. Compared to the 1990 resident population of California-born resident singletons, the respondents were of similar age, sex, race and residential distribution (for although we were able to locate fewer older females, they had a higher response rate), but were less likely to have been educated for more than 12 years. We provide a brief synopsis of studies nested within this cohort. We also elucidate our plans for expanding the cohort in the near future.     

Does higher concordance in monozygotic twins than in dizygotic twins suggest a genetic component?

It is widely regarded that twins can be used as a natural experiment to subject hypotheses to empirical testing regarding the contributions of genetic factors to phenotypic variability in human traits, especially behavioral traits. In genetic epidemiology, a higher concordance rate in monozygotic (MZ) twins than in dizygotic (DZ) twins is often taken as prima facie evidence for a genetic component. While twins studies have been used to estimate the contributions of genetic factors to phenotypic variability in human traits, the corresponding methodology that allows the estimation entails several crucial assumptions. The most critical is that MZ and DZ twins are equally similar environmentally. Although MZ twins are genetically more similar than DZ twins, they are often environmentally more similar. This paper demonstrates that, even in the complete absence of any genetic factor and of any biases, the greater environmental similarity alone in MZ twins can result in higher concordance rate in MZ twins than in DZ twins. This is especially true when there are multiple environmental factors, which may have multiple exposure levels and/or interact strongly, although each of them may be of low risk. This may serve as a sobering antidote to the uncritical reliance on twin studies without examining the validity of the underlying assumptions.     

Genetic and environmental influences on bilateral dental asymmetry in Northwest Indian twins

The role of genetic and environmental factors on dental asymmetry (in maximum crown dimensions) was examined using 58 pairs of twins (23 MZ and 35 DZ) from Chandigarh, India. The t'-test for equality of means by zygosity showed only one variable significantly different among 56: this is ascribable to Type 1 error. Heterogeneity of MZ-DZ total variance was observed in 42.9% of traits of the two types (fluctuating and directional) of bilateral asymmetry. In general, MZ twins showed higher total variance than DZ pairs. MZ twins also showed stronger environmental covariance for a majority of the traits. Dental asymmetry measures thus yielded consistently low genetic variance ratios and indicated predominantly complex environmental determinism. Since fluctuating asymmetry is widely believed to be an environmental stress indicator, this data set allows confirmation of methods for detecting unequal environmental influences on the zygosities which bias estimates of genetic variance and heritability.     

Inheritance of body size in the Barnacle Goose under different environmental conditions

Heritabilities, genetic variances and covariances for body size traits, i.e. tarsus length, head length and body mass, were estimated under different environmental conditions in a Barnacle Goose (Branta leucopsis) population. Under poor growth conditions, that is, when average body size of fully grown offspring in a given cohort was small, the offspring-parent regressions and full-sib analyses yielded heritability estimates not significantly different from zero. By contrast, when growth conditions were normal or good the heritability estimates were generally significantly positive. Comparisons of genetic covariance estimates indicated that they also differed across the analysed environmental conditions. This result, together with similar results obtained in studies of passerine birds, suggests that genotype-environment interactions might be frequent within the range of environments normally encountered by birds in natural populations. If general, such results might question the validity of assuming approximate constancy of additive genetic variances and covariances over time and environments in evolutionary models.     

A rare case of heteropaternal twin calves after natural mating in Brazil

Twin birth is a complex condition observed in most livestock animals, when the female gives birth to two or more offspring, generally out of the same mating. In cattle, it is a rare condition (3 to 5%) and depends on the genetic background and environmental factors. Twin birth is a result of multiple ovulations, being more common in dairy rather than in beef cattle. Calves could be monozygous or dizygous, with the same or of different sexes. When twins are born with different sexes, a sexual condition called Freemartinism occurs in between 90 to 97% of pregnancies, causing infertility in the female calf. Knowing that the twin rate is rare in commercial beef cattle, here we present an even rarer case of twin birth from two different sires after natural mating, also called heteropaternal superfecundation.     

Sex differences in birth defects: a study of opposite-sex twins

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.     

Pets and Our Mental Health: The Why,the What and the How

ABSTRACT

There is growing evidence that pet ownership and human–animal interaction (HAI) have benefits for human physical and psychological well-being. However, there may be pre-existing characteristics related to patterns of pet ownership and interactions with pets that could potentially bias results of research on HAI. The present study uses a behavioral genetic design to estimate the degree to which genetic and environmental factors contribute to individual differences in frequency of play with pets among adult men. Participants were from the ongoing longitudinal Vietnam Era Twin Study of Aging (VETSA), a population-based sample of 1,237 monozygotic (MZ) and dizygotic (DZ) twins aged 51–60 years. Results demonstrate that MZ twins have higher correlations than DZ twins on frequency of pet play, suggesting that genetic factors play a role in individual differences in interactions with pets. Structural equation modeling revealed that, according to the best model, genetic factors accounted for as much as 37% of the variance in pet play, although the majority of variance (63–71%) was due to environmental factors that are unique to each twin. Shared environmental factors, which would include childhood exposure to pets, overall accounted for <10% of the variance in adult frequency of pet play, and were not statistically significant. These results suggest that the effects of childhood exposure to pets on pet ownership and interaction patterns in adulthood may be mediated primarily by genetically-influenced characteristics.