The genetic contribution of blood pressure and heart rate (HR) varied widely between studies. Demographic factors such as ethnicity, age and/or sex might explain some of the heterogeneity. We performed a systematic review focusing on four phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), HR and pulse pressure (PP). Meta-regression was conducted to analyze potential factors in relation to SBP and DBP heritability. A total of 10,613 independent twins that came from 17 studies were included in the analysis. The weighted mean value of heritability for SBP and DBP was 0.54 (95% CIs: 0.48–0.60) and 0.49 (95% CIs: 0.42–0.56). Comparatively, three studies of HR and four studies of PP heritability were limited for the heterogeneity test. Meta-regression showed that, on average, SBP heritability with additive genes/unique environment (AE) model tend to have a higher heritability than additive genes/shared environment/unique environment (ACE) model (coefficient = 0.0947, p = .0142). A similar result was found for DBP as well. No other factors such as sex, age, ethnicity, publication year were significantly associated with heritability variance. Our study shows heritability estimates based on twin studies of both SBP and DBP are around 50%, using an AE rather than an ACE model; the variance due to C ended up in A, suggesting that the AE model may overestimate heritability if a small contribution of shared environment exists.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56–58%), who had smoked but did not smoke during a particular pregnancy (16–21%), or who smoked throughout the pregnancy (16–18%), were in good agreement whether based on selfreport or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1–3% versus 7–9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.

The Healthy Twin Study, Korea (HT) is an ongoing multi-center cohort study that was initiated in 2005, based on a nation-wide twin and family database. Since its inception, the HT has recruited 815 pairs of adult twins and a total of 3,690 individual twins and their families as of July 2012. Here we summarize updates since the previous report in 2006. Besides the increase in size, the HT has been enriched in several aspects: a biobank was constructed for ongoing and future omics studies; and genome-wide single nucleotide polymorphism markers (Affymetrix GeneChip version 6.0, 1 M probes) have been analyzed for 2,200 individuals, which enabled gene identification studies for measured phenotypes. In addition, longitudinal study protocols were established through the HT and a second wave survey was finished in 2010 with >70% follow-up rate. The parallel genome research projects were recently launched, which would expedite multi-omics studies maximizing the twin potentials such as metagenomics and epigenetics studies, and endow us with resources for recruiting more participants. We submit this report to share updates and research opportunities from the HT.

The Nonshared Environment in Adolescent Development (NEAD) project is a longitudinal study of twins/siblings and parents that has been assessed 3 times: middle adolescence, late adolescence and young adulthood (N = 720 families at Time 1). Siblings varied in degree of genetic relatedness including identical twins, fraternal twins, full siblings, half siblings and genetically unrelated (or step) siblings. There were also two family types: nondivorced and step. A multimeasure, multirater approach was taken in NEAD, with data collected from all participants (2 twins or siblings, mother and father) as well as from coded videotaped observations of family interactions. Detailed assessments of family relationships, adolescent adjustment and competence were collected at all 3 times. The original aim of NEAD was to identify systematic sources of nonshared environmental influences that contribute to differences among family members. Although systematic sources of nonshared environmental influences were not found in NEAD, three major sets of findings emerged: (1) genetic influences on family relationships and on associations between family relationships and adolescent adjustment; (2) genetic and environmental influences on adolescent adjustment, comorbidity and stability and change in adolescent adjustment from middle to late adolescence; and (3) genetic influences on relationships outside the family.

Several common adult diseases appear to be related to impaired fetal growth and this may be caused either by nutritional inadequacies at particular stages of pregnancy or by variation in alleles at specific growth loci. Little is known about the genes involved in the underlying mechanism. This review proposes that at least some of the effects have their origins at imprinted loci, genes that are unusual because they are expressed from only one parental allele. Many imprinted genes are crucial for fetal growth and determine birthweight. They can be disrupted in the early embryo by environmental influences and these disruptions can be inherited through many cell cycles into adult tissues. Their disruption can affect specific organs during fetal development and disruption could affect adult disease in a variety of direct and indirect means. Imprinted genes may be particularly vulnerable to disruption as they are functionally haploid and their expression is regulated by different means from the rest of the genome. Thus many imprinted genes provide plausible candidates for programming adult disease and warrant further study in this context.

The effects on sleep pattern (‘short-sleep’ versus ‘long-sleep’) and subjective sleep disturbance of genotype, personality, symptoms of anxiety and depression, and lifestyle, were examined using survey data on a clinically unselected sample of adult Australian twin pairs, aged 17–88 years. When the effects of genotype, personality and symptoms were ignored, lifestyle variables appeared to account for roughly 4% of the variance in sleep disturbance, and 9% of the variance in sleep pattern. Significant genetic effects on sleep disturbance and sleep pattern were found, which were only partly explained by the effects of personality and symptoms of anxiety and depression. Much of the association between sleep disturbance and lifestyle appeared to be explained by separate effects of personality and symptoms of anxiety and depression on sleep and lifestyle (‘genotype – risk-factor correlation’). There was little evidence for genetically determined differences in sensitivity to the lifestyle variables (‘genotype × risk-factor interaction’).

Longitudinal height and weight data from 4649 Dutch twin pairs between birth and 2.5 years of age were analyzed. The data were first summarized into parameters of a polynomial of degree 4 by a mixed-effects procedure. Next, the variation and covariation in the parameters of the growth curve (size at one year of age, growth velocity, deceleration of growth, rate of change in deceleration [i.e., jerk] and rate of change in jerk [i.e., snap]) were decomposed into genetic and nongenetic sources. Additionally, the variation in the estimated size at birth and at 2 years of age interpolated from the polynomial was decomposed into genetic and nongenetic components. Variation in growth was best characterized by a genetic model which included additive genetic, common environmental and specific environmental influences, plus effects of gestational age. The effect of gestational age was largest for size at birth, explaining 39% of the variance. The differences between monozygotic and dizygotic twin correlations were largest for size at 1 and 2 years of age and growth velocity of weight, which suggests that these parameters are more influenced by heritability than size at birth, deceleration and jerk. The percentage of variance explained by additive genetic influences for height at 2 years of age was 52% for females and 58% for males. For weight at 2 years of age, heritability was approximately 58% for both sexes. Variation in snap height for males was also mainly influenced by additive genetic factors, while snap for females was influenced by both additive genetic and common environmental factors. The correlations for the additive genetic and common environmental factors for deceleration and snap are large, indicating that these parameters are almost entirely under control of the same additive genetic and common environmental factors. Female jerk and snap, and also female height at birth and height at 2 years of age, are mostly under control of the same additive genetic factor.

Most analyses of data collected from a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins assume that zygosity has been diagnosed without error. However, large scale surveys frequently resort to questionnaire-based methods of diagnosis which classify twins as MZ or DZ with less than perfect accuracy. This article describes a mixture distribution approach to the analysis of twin data when zygosity is not perfectly diagnosed. Estimates of diagnostic accuracy are used to weight the likelihood of the data according to the probability that any given pair is either MZ or DZ. The performance of this method is compared to fully accurate diagnosis, and to the analysis of samples that include some misclassified pairs. Conventional analysis of samples containing misclassified pairs yields biased estimates of variance components, such that additive genetic variance (A) is underestimated while common environment (C) and specific environment (E) components are overestimated. The bias is non-trivial; for 10% misclassification, true values of Additive genetic: Common environment: Specific Environment variance components of .6: .2: .2 are estimated as .48: .29: .23, respectively. The mixture distribution yields unbiased estimates, while showing relatively little loss of statistical precision for misclassification rates of 15% or less. The method is shown to perform quite well even when no information on zygosity is available, and may be applied when pair-specific estimates of zygosity probabilities are available.

In two studies, the General Factor of Personality (GFP) remained intact after controlling for the Lie scale from the Eysenck Personality Questionnaire, despite the Lie Scale showing significant correlations with the GFP defining traits. In Study 1, a re-analysis of 29 self-ratings from 322 pairs of twins (644 individuals) yielded a GFP both before and after controlling for social desirability. In Study 2, four measures of affect in 133 university students loaded on a GFP both before and after controlling for social desirability such that those high on the GFP were high in self-esteem and positive affect and low in depression and negative affect. These results join those from other studies failing to find evidence that the GFP is merely an artifact of evaluative bias.

Telegenetics is a new development in the service delivery of Genetic Services in Australia. This project was designed to establish if it was an acceptable alternative to a face-to-face consultation in the genetic assessment of intellectual disability, including morphological assessment, of the patient. Ten children from two outreach clinics in rural NSW who were referred by their pediatrician were assessed by a single geneticist via telehealth and then seen again face-to-face as a ‘gold standard'. Satisfaction surveys were then sent to both the parents and the referring pediatricians. After the face-to-face appointment, the clinical geneticist reviewed the recordings of both the transmitted footage and the high definition footage that was sent separately. There were very few morphological findings missed by the telegenetic assessments. The discrepancies that were noted could decrease in frequency as staff become more familiar with the methods. The parents of the patients reported no problem with the cameras and telehealth. They would have preferred face-to-face appointment but would be happy to have the telehealth appointment if it meant being seen earlier. This pilot study suggests that clinical genetic diagnostic assessment could be performed by telemedicine.

Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterize the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine™ screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine, or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53–60%) and 42% (95% CI: 37–46%), respectively. A significant additive genetic correlation (rG = 0.36, 95% CI: 0.29–0.43) and bivariate heritability (h2 = 5.5%, 95% CI: 3.6–7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h2 (13.3%, 95% CI: 7.0–24.5%) and rG (0.51, 95% CI: 0.37–0.69) estimates significantly increased when analyzing the more narrow clinically accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms.

High density single nucleotide polymorphism (SNP) genotyping panels provide an alternative to microsatellite markers for genome scans. However, genotype errors have a major impact on power to detect linkage or association and are difficult to detect for SNPs. We estimated error rates with the Affymetrix GeneChip® SNP platform in samples from a family with a mixed set of monozygotic (MZ) and dizygotic (DZ) triplets using lymphocyte, buccal DNA and samples from whole genome amplification using the multiple displacement amplification (MDA) technique. The average call rate from 58,960 SNPs for five genomic samples was 99.48%. Comparison of results for the MZ twins showed only three discordant genotypes (concordance rate 99.995%). The mean concordance rate for comparisons of samples from lymphocyte and buccal DNA was 99.97%. Mendelian inconsistencies were identified in 46 SNPs with errors in one or more family members, a rate of 0.022%. Observed genotype concordance rates between parents, between parents and children, and among siblings were consistent with previously reported allele frequencies and Hardy–Weinberg equilibrium. Using the MDA technique, results for two samples had equivalent high accuracy to results with genomic samples. However, the SNP call rate for the remaining seven samples varied from 72.5% to 99.5%, with an average of 86.11%. Quality of the DNA sample following the MDA reaction appears to be the critical factor in SNP call rate for MDA samples. Our results demonstrate highly accurate and reproducible genotyping for the Affymetrix GeneChip® Human Mapping Set in lymphocyte and buccal DNA samples.

Asurge in the search for endophenotypes for psychiatric disorders has occurred in the past several years. An important criterion of an endophenotype is that it is heritable. Two of the most widely used executive cognitive functioning measures are the Wisconsin Card Sorting Test (WCST) and the Stroop Color-Word Test. Each has been considered as a possible endophenotype. However, research on the heritability of each of these measures is sparse, and in the case of the WCST, mixed. As part of a pilot twin study examining cognitive functioning and personality in adults, the WCST and the Stroop were administered to 80 monozygotic and 29 dizygotic twin pairs screened for absence of neurological disease and head injury. Results replicated and extended previous findings for moderate heritability of Stroop performance. However, the WCST showed little evidence of genetic influence, suggesting that it might not meet one of the criteria for an endophenotype.

The unique opportunity given by the “fiscal code”, an alphanumeric identification with demographic information on any single person residing in Italy, introduced in 1976 by the Ministry of Finance, allowed a database of all potential Italian twins to be created. This database contains up to now name, surname, date and place of birth and home address of about 1,300,000 “possible twins”. Even thought we estimated an excess of 40% of pseudo-twins, this still is the world's largest twin population ever collected. The database of possible twins is currently used in population-based studies on multiple sclerosis, Alzheimer's disease, celiac disease, and type 1 diabetes. A system is currently being developed for linking the database with data from mortality and cancer registries. In 2001, the Italian Government, through the Ministry of Health, financed a broad national research program on twin studies, including the establishment of a national twin registry. Among all the possible twins, a sample of 500,000 individuals are going to be contacted and we expect to enrol around 120,000 real twin pairs in a formal Twin Registry. According to available financial resources, a sub sample of the enrolled population will be asked to donate DNA. A biological bank from twins will be then implemented, guaranteeing information on future etiological questions regarding genetic and modifiable factors for physical impairment and disability, cancers, cardiovascular diseases and other age related chronic illnesses.

The objective of this study was to determine if mothers' retrospective reports about events in their pregnancies with twins are reliable and stable. Six hundred and twenty-four mothers completed psychiatric interviews about their twins. These interviews also contained questions about the mothers' pregnancies, the perinatal period, and the child's early development. The mothers reported first on one twin and then on the other with interviews spaced from 3 days to 2 weeks apart. Thus mothers reported on the same pregnancy twice. Of these mothers, 47 were re-interviewed 6 to 18 months later by raters blind to the results of the initial interview. The twin design allowed us to compare the short-term reliability of the 624 mothers' reports of the same pregnancy. The re-interview of the 47 mothers enabled us to compare the stability of reports over a longer time period. Agreement between the reports was measured with the kappa statistic. Kappas were good to excellent for the short-term reports of pregnancy for each twin for the 624 mothers. Kappas were equally high for the 47 mothers that were re-interviewed 6 to 18 months later. Mothers show good reliability and stability of reporting about events during pregnancy.

In previous studies we obtained evidence that variation in loneliness has a genetic component. Based on adult twin data, the heritability estimate for loneliness, which was assessed as an ordinal trait, was 48%. These analyses were done on loneliness scores averaged over items (‘I feel lonely’ and ‘Nobody loves me’) and over time points. In this article we present a longitudinal analysis of loneliness data assessed in 5 surveys (1991 through 2002) in Dutch twins (N = 8389) for the two separate items of the loneliness scale. From the longitudinal growth modeling it was found sufficient to have non-zero variance for the intercept only, while the other effects (linear, quadratic and cubic slope) had zero variance. For the item ‘I feel lonely’ we observed an increasing age trend up to age 30, followed by a decline to age 50. Heritability for individual differences in the intercept was estimated at 77%. For the item ‘Nobody loves me’ no significant trend over age was seen; the heritability of the intercept was estimated at 70%.

This study was performed to determine the rates of breastfeeding among singletons, twins and triplets in Japan, and identify factors associated with the decision to breastfeed or bottle-feed. We analyzed a database of medical check-up of infants aged 3 to 6 months between April 2001 and July 2004 in Nishinomiya City in Japan. This medical check-up is given to almost 100% of infants in Japan and the data of 15,262 infants were analyzed. Among these, 14,963 (98.0%) were singletons, 290 (1.9%) were twins and 9 (0.1%) were triplets. Exclusive breast-feeding was chosen by 6680 (43.8%) mothers, mixed-feeding by 4645 (30.4%) mothers, and bottle-feeding with formula milk only by 3900 (25.6%) mothers. The rate of exclusive breastfeeding among twins or triplets was significantly lower than among singleton babies: 4.1% among twins or triplets, and 44.7% among singletons. Moreover, twins and triplets were independently associated with a higher rate of bottle-feeding: the odds ratio indicated that mothers who had twins or triplets were 2.44 times more likely to choose bottle-feeding with formula milk only than those who had singletons. Sucking ability at birth was associated with a higher rate of bottle-feeding: the odds ratio indicated that mothers who had infants with poor sucking ability at birth were 1.56 times more likely to choose bottle-feeding as those who had infants with normal sucking ability.

The physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2 ± 2.3 vs. 11.0 ± 4.1 MET h/day, p < .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO2peak 26.4 ± 4.9 vs. 32.5 ± 5.5 ml/kg/min, p < .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.

We examined whether effortful control (EC), a temperament proposed by Rothbart and Bates (1998), has genetically coherent structure. A self- report measure of EC was administered to 450 Japanese twins (151 males and 299 females, ages 17 to 32 years) including 152 monozygotic and 73 dizygotic pairs. Univariate genetic analysis revealed that AE model fit best for the total EC as well as its subscales. The heritability estimate for total EC was 49%, and the estimates for subscales ranged between 32% and 45%. Multivariate genetic analysis revealed that the subscales of EC were genetically correlated to a high degree and environmentally correlated to a moderate degree. These results suggest that EC has substantial genetic basis and genetically coherent structure, supporting the validity of the construct. The implications to molecular genetic study and study of psychopathology were discussed.

Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation — one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits — prosocial behaviour, peer problems, and verbal ability — have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.