We describe the prevalence of chronic diseases and conditions in a large cohort of twins, which has been developed to facilitate studies of the role of genetics and environment in the development of disease. The California Twin Program (CTP) comprises twins born in California between 1908 and 1982. Birth records from all multiple births (256,616 in total) were linked (multiple times between 1990 and 2001) with the California Department of Motor Vehicles (DMV) roster of licensees to obtain address information. The linkages have revealed 161,109 matches and, because of less complete DMV records in some years, were less successful in older females than in all others. To date over 51,000 of these twins have completed a detailed 16-page mailed risk factor questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, our crude response rates are as high as 63.6% (among females currently in their 50s), with an overall crude response rate of 37.9%. Similar to our previous report regarding the first 42,000 twins, the current group who have completed the questionnaire are representative of the population from which they were drawn (in terms of age, sex, race and residential distribution). Self-reported disease frequencies are provided, along with current estimates of future cancer incidence and mortality rates likely to be observed in the group. We outline our plans for cohort expansion, additional studies using the cohort, and future plans for inviting collaboration.

The ratio of the lengths of the second to fourth digits of the hand (2D:4D) is a sexually dimorphic trait that has been proposed as a measure of prenatal testosterone exposure and a putative correlate of a variety of later behavioral and physiological outcomes including personality, fitness and sexual orientation. We present analyses of 2D:4D ratios collected from twins (1413 individuals) and their nontwin siblings (328 individuals) from 757 families. In this sample 2D:4D was measured from photocopies using digital calipers, and for a subset of participants, computer-aided measurement. Multivariate modeling of the left- and right-hand measurements revealed significant genetic and environmental covariation between hands. The two methods yielded very similar results, and the majority of variance was explained by factors shared by both measurement methods. Neither common environmental nor dominant genetic effects were found, and the covariation between siblings could be accounted for by additive genetic effects accounting for 80% and 71% of the variance for the left and right hands, respectively. There was no evidence of sex differences in the total variance, nor in the magnitude or source of genetic and environmental influences, suggesting that X-linked effects (such as the previously identified association with the Androgen receptor) are likely to be small. However, there were also nonshared environmental effects specific to each hand, which, in addition to measurement error, may in part explain why some studies within in the literature find effects for the 2D:4D ratio of one hand but not the other.

Twin pregnancies are becoming common as a result of increased assisted reproduction. Studies have shown that the smaller twin of a pair is at greater risk of morbidity and mortality. Our aim was to determine if there is a relation between birth-weight discordancy and neonatal morbidity and mortality and to test the occurrence of respiratory distress syndrome (RDS) in discordant twins. For 5 years all twins admitted to our intensive care unit were included in the study. Discordance was calculated as the difference between twins' weights divided by the heavier weight. Diagnosis of RDS was made by typical clinical and radiographic methods. Multiple logistic regression was performed with gender, weight order and birth order as the independent variables and RDS as the dependent variable. Two hundred and sixty-six twin pairs with a mean gestation of 33 weeks and a mean birthweight of 1890 g were evaluated. Multiple logistic regression revealed that being the heavier twin was a more important risk factor for RDS (odds ratio 4.5; 95% confidence interval 2.2–9.2) than being the male or second-born twin. Based on neonatal outcomes a birthweight discordance equal or greater than 20% in twin pairs was accepted as the discordance criterion. Discordant and concordant groups were statistically different in neonatal mortality, necrotizing enterocolitis, polycytemia and hypoglycemia. Our data demonstrated that being the heavier twin is a risk factor for RDS and a birth-weight difference of 20% or more in twin pairs should be accepted as discordance.

The East Flanders Prospective Twin Survey (EFPTS) is a prospective, population-based registry of multiple births in the province of East-Flanders, Belgium. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at −20 °C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic–diamnionic pairs (early, with splitting before the fourth day after fertilization), the monochorionic–diamnionic pairs (intermediate, splitting between the fourth and the seventh day post-fertilization), and the monochorionic–monoamnionic pairs (late, splitting after the eighth day post-fertilization). Studies can be initiated taking into account primary biases, those originating ‘in utero’. Such studies could throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events, and the gene–environment interactions as far as periconceptional and intrauterine environment are concerned.

Genes involved in pathways regulating body weight may operate differently in men and women. To determine whether sex-limited genes influence the obesity-related phenotype body mass index (BMI), we have conducted a general non- scalar sex-limited genome-wide linkage scan using variance components analysis in Mx (Neale, 2002). BMI measurements and genotypic data were available for 2053 Australian female and male adult twins and their siblings from 933 families. Clinical measures of BMI were available for 64.4% of these individuals, while only self-reported measures were available for the remaining participants. The mean age of participants was 39.0 years of age (SD 12.1 years). The use of a sex-limited linkage model identified areas on the genome where quantitative trait loci (QTL) effects differ between the sexes, particularly on chromosome 8 and 20, providing us with evidence that some of the genes responsible for BMI may have different effects in men and women. Our highest linkage peak was observed at 12q24 (–log10p = 3.02), which was near the recommended threshold for suggestive linkage (–log10p = 3.13). Previous studies have found evidence for a quantitative trait locus on 12q24 affecting BMI in a wide range of populations, and candidate genes for non- insulin-dependent diabetes mellitus, a consequence of obesity, have also been mapped to this region. We also identified many peaks near a –log10p of 2 (threshold for replicating an existing finding) in many areas across the genome that are within regions previously identified by other studies, as well as in locations that harbor genes known to influence weight regulation.

The human electroencephalogram (EEG) consists of oscillations that reflect the summation of postsynaptic potentials at the dendritic tree of cortical neurons. The strength of the oscillations (EEG power) is a highly genetic trait that has been related to individual differences in many phenotypes, including intelligence and liability for psychopathology. Here, we investigated whether brain anatomy underlies these EEG power differences by correlating it to gray and white matter volumes (GMV, WMV), and additionally investigated whether this association can be attributed to genes or environmental factors. EEG was measured in a sample of 405 young adult twins and their siblings, and power in the theta (~4 Hz), alpha (~10 Hz), and beta (~20 Hz) frequency bands determined. A subset of 121 subjects were also scanned in a 1.5 T MRI scanner, and gray and white matter volumes defined as the total of cortical and subcortical volumes, excluding cerebellum. Both MRI-based volumes and EEG power spectra were highly heritable. GMV and WMV correlated .25 to .29 with EEG power for the slower oscillations (theta, alpha). Moreover, these phenotypic correlations largely reflected genetic covariation, irrespective of oscillation frequency and volume type. Genetic correlations (.31 < rA < .43) revealed that only moderate proportions of the heritable variance overlapped between MRI volumes and EEG power. The results suggest that MRI volumes and EEG power share genetic sources of variation, which may reflect such processes as myelination, synaptic density, and dendritic outgrowth.

Thirteen sets of monozygotic (MZ) twins from an extended multi-generation family are reported. Zygosity was determined by interviewing families for overall physical similarity and by assessment of facial photographs. A hypothetical gene was traced back five generations to a common grandfather. Familial monozygotic twinning in this pedigree is compatible with autosomal dominant inheritance with reduced penetrance. Other plausible mechanisms of inheritance are discussed.

Birth weight is in large extent influenced by gestational age. In addition genetic and environmental factors determine intrauterine growth and birth weight. The contributions of these factors may be influenced by maternal smoking during pregnancy. We examined birth weight and maternal smoking in a sample of 2930 twin pairs from the Netherlands Twin Register using structural equation modelling. Gestational age accounted for 27–44% of the variance in birth weight. A lower variability of birth weight and a lower association of birth weight with gestational age was found in twins whose mothers smoked during pregnancy. The variance not associated with gestational age was independent of maternal smoking during pregnancy. A systematic smaller part of the variability in birth weight was associated with variability in gestational age in second born twins compared to first born twins. The heritability of interindividual differences in birth weight was modest (10% for twins with non-smoking mothers and 11% for twins with smoking mothers). Common environmental influences other than gestational age accounted for a slightly larger part of the variance not associated with gestational age (17–20%).

In humans, in contrast to animals, the genetic influences on infidelity are unclear. We report here a large study of over 1600 unselected United Kingdom female twin pairs who confidentially reported previous episodes of infidelity and total lifetime number of sexual partners, as well as attitudes towards infidelity. Our findings demonstrate that infidelity and number of sexual partners are both under moderate genetic influence (41% and 38% heritable, respectively) and the genetic correlation between these two traits is strong (47%). Conversely, attitudes towards infidelity are driven by shared and unique environmental, but not genetic, influences. A genome-wide linkage scan identified three suggestive but nonsignificant linkage areas associated with infidelity and number of sexual partners on chromosomes 3, 7 and 20 with a maximum LOD score of 2.46. We were unsuccessful in associating infidelity or number of sexual partners with a locus implicated in other mammals' sexual behavior, the vasopressin receptor gene. Nonetheless, our findings on the heritabil-ity of sexual infidelity and number of sexual partners provide support for certain evolutionary theories of human sexual behavior, as well as justifying further genetic and molecular research in this domain.

We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix® Human SNP 6.0 arrays™ were analyzed using Affymetrix® Genotyping Console™, Partek® Genomics Suite™, PennCNV, and Golden Helix SVS™. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development.

There has been almost no overlap between behavior genetics and consumer behavior research, despite each field's importance in understanding society. In particular, both have neglected to study genetic influences on consumer adoption and usage of new technologies — even technologies as important as the mobile phone, now used by 5.8 out of 7.0 billion people on earth. To start filling this gap, we analyzed self-reported mobile phone use, intelligence, and personality traits in two samples of Australian teenaged twins (mean ages 14.2 and 15.6 years), totaling 1,036 individuals. ACE modeling using Mx software showed substantial heritabilities for how often teens make voice calls (.60 and .34 in samples 1 and 2, respectively) and for how often they send text messages (.53 and. 50). Shared family environment – including neighborhood, social class, parental education, and parental income (i.e., the generosity of calling plans that parents can afford for their teens) — had much weaker effects. Multivariate modeling based on cross-twin, cross-trait correlations showed negative genetic correlations between talking/texting frequency and intelligence (around –.17), and positive genetic correlations between talking/texting frequency and extraversion (about .20 to .40). Our results have implications for assessing the risks of mobile phone use such as radiofrequency field (RF) exposure and driving accidents, for studying adoption and use of other emerging technologies, for understanding the genetic architecture of the cognitive and personality traits that predict consumer behavior, and for challenging the common assumption that consumer behavior is shaped entirely by culture, media, and family environment.

Our work assessed the accuracy of the original zygosity classification in the Vietnam Era Twin (VET) Registry using new information from DNA markers on a subset of participants. We then constructed an updated zygosity classification algorithm. The VET Registry includes 7,375 male–male twin pairs who served in the military during the Vietnam era. During the mid-1980s 4,774 twin pairs completed a zygosity questionnaire of 20 items. Additionally, military record information, including blood group, was available. Items from the zygosity questionnaire and blood group were used in the original zygosity classification. Between 1990–2009 DNA was obtained from 612 twin pairs and concordance between co-twins was used to classify zygosity. Next logistic regression was used to construct predicted probabilities of zygosity using items from the zygosity questionnaire with this subsample. All twins were reclassified according to the new zygosity prediction model and compared with the original zygosity assignment. The original and new predicted probabilities of zygosity were highly correlated (r = 0.962) and concordance for the classification of zygosity was similarly high (kappa = 0.936). Errors in the original zygosity assignment were primarily due to monozygotic twins that were misclassified as dizygotic based on military record blood group data. Removing the military record blood group data markedly improved the accuracy of the original classification. Zygosity assignment based on a zygosity questionnaire was highly predictive of DNA-based zygosity. Augmentation of such a zygosity classification from administrative data, military records, or other records, should be done with caution.

Placental vascular anastomoses in twins lead to a shared circulation and may subsequently enable the development of severe complications such as twin–twin transfusion syndrome (TTTS) and twin anemia–polycythemia sequence (TAPS). The presence of vascular anastomoses has frequently and systematically been studied in monochorionic (MC) placentas, but only rarely in dichorionic (DC) placentas. The aim of this study was to compare the prevalence of vascular anastomoses and evaluate the sharing discordance in MC and DC placentas. All consecutive placentas of MC and DC twins delivered at the Leiden University Medical Center (the Netherlands) and Medical University of Warsaw (Poland) from 2012 to 2015 were routinely injected with colored dye and included in the study. We excluded twin pregnancies treated with fetoscopic laser surgery. A total of 258 placentas were analyzed in this study, including 134 MC placentas and 124 DC placentas. Vascular anastomoses were present in 99% (133/134) of MC placentas and 0% of DC placentas (p < .01). Placental share discordance between MC twins was significantly larger compared to DC twins, 19.8 (interquartile range [IQR] 8.1–33.3) and 10.8 (IQR 6.2–19.0), respectively (p < .01). Vascular anastomoses associated complications occurred in 16% (22/134) MC twins. Our findings show that vascular anastomoses are almost ubiquitous in MC placentas, but non-existent in DC placentas. In addition, unequal placental sharing appears to be more common in MC than in DC placentas.

The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men, particularly early identification of risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). It comprises a subset of over 1600 twins from the Vietnam Era Twin Registry. Twins live all over the USA. Assessments began when participants were in their 50s. Follow-ups were conducted every 5–6 years, and wave 3 has been completed as of this writing. The age range of participants is narrow (about 10 years). An extensive neurocognitive test battery has added precision in assessing differences in middle-aged adults, and predicting progression to MCI. Young adult cognitive test data (at an average age of 20 years) provide a means of disentangling aging effects from longstanding differences. Genome wide genotyping and plasma assays of AD biomarkers from waves 1 and 3 were conducted in wave 3. These features make the VETSA ideal for studying the heterogeneity of within-individual trajectories from midlife to old age, and for early detection of risk factors for cognitive decline.

Visual impairment is a leading cause of morbidity and poor quality of life in our community. Unravelling the mechanisms underpinning important blinding diseases could allow preventative or curative steps to be implemented. Twin siblings provide a unique opportunity in biology to discover genes associated with numerous eye diseases and ocular biometry. Twins are particularly useful for quantitative trait analysis through genome-wide association and linkage studies. Although many studies involving twins rely on twin registries, we present our approach to the Twins Eye Study in Tasmania to provide insight into possible recruitment strategies, expected participation rates and potential examination strategies that can be considered by other researchers for similar studies. Five separate avenues for cohort recruitment were adopted: (1) piggy-backing existing studies where twins had been recruited, (2) utilizing the national twin registry, (3) word-of-mouth and local media publicity, (4) directly approaching schools, and finally (5) collaborating with other research groups studying twins.

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 56,000 twins primarily born or living in Virginia, North Carolina, and South Carolina. The MATR employs several methods of ascertaining twins, and devotes considerable resources to tracking and maintaining communication with MATR participants. Researchers may utilize the MATR for administration of research services including study recruitment, collection of DNA, archival data set creation, as well as data collection through mailed, phone, or online surveys. In addition, the MATR houses the MATR Repository, with over 1,200 blood samples available for researchers interested in DNA genotyping. For over 35 years MATR twins have participated in research studies with investigators from diverse scientific disciplines and various institutions. These studies, which have resulted in numerous publications, have covered a range of topics, including the human microbiome, developmental psychopathology, depression, anxiety, substance use, epigenetics of aging, children of twins, pre-term birth, social attitudes, seizures, eating disorders, as well as sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.

Absolute pitch is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We sought to further investigate the hypothesis that genetic factors support the acquisition of absolute pitch and to better elucidate the inheritance pattern of this trait. To this end, we conducted a twin study and a segregation analysis using data collected from a large population of absolute pitch possessors. The casewise concordance rate of 14 monozygotic twin pairs, 78.6%, was significantly different from that of 31 dizygotic twin pairs, 45.2%, assuming single ascertainment (x2 = 5.57, 1 df, p = .018), supporting a role for genetics in the development of absolute pitch. Segregation analysis of 1463 families, assuming single ascertainment, produced a segregation ratio pD = .089 with SEpD = 0.006. Unlike an earlier segregation analysis on a small number of absolute pitch probands from musically educated families, our study indicates that absolute pitch is not inherited in a simple Mendelian fashion. Based on these data, absolute pitch is likely genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis. These findings are in agreement with the results of our recent linkage analysis.

Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.

A prospective study of 692 male twins was undertaken to investigate the relationships among early adolescent problem behavior, contextual risk, and disinhibitory psychopathology. Early adolescent problem behavior was assessed by the number of the following behaviors engaged in by the time of the age-14 assessment: (1) tobacco use, (2) alcohol use, (3) marijuana use, (4) other illicit drug use, (5) sexual intercourse, and (6) police contact. Contextual risk was assessed as a composite of measures of peer models, parent-offspring conflict, and academic engagement from the age-14 assessment. Disinhibitory psychopathology was assessed by symptoms of nicotine dependence, alcohol dependence, drug dependence, and adult antisocial behavior at the age-18 assessment. Early adolescent problem behavior and contextual risk were strongly correlated (r = .53) and both were strongly and independently associated with symptoms of disinhibitory psychopathology (r from .35 to .60). The association of early adolescent problem behavior with both contextual risk and disinhibitory psychopathology was mediated entirely by genetic factors while the association between contextual risk and disinhibitory psychopathology was mediated by both genetic and nonshared environmental factors. The results are discussed in the context of emerging research on the prognostic significance of early adolescent problem behavior for risk of adult psychopathology.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.