Background: Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at uncovering the genetic contributions of adhesion molecules, key members in the inflammatory process, to PWV in these young individuals. Methods: Radial and foot PWV were noninvasively measured with applanation tonometry in 702 black and white subjects (42% blacks, mean age 17.7 ± 3.3 years) from the Georgia Cardio vascular Twin Study. Eight functional polymorphisms from genes for E-selectin (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and vascular cell adhesion molecules-1 (VCAM1) were genotyped. Results: Youth with Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an increase in both radial and foot PWV (6.61 ± 0.07 vs. 6.41 ± 0.05 m/s, p = .026; 7.22 ± 0.05 vs. 7.04 ± 0.04 m/s, p = .007). TT homozygotes of rs2244529 (SELP) had higher foot PWV (7.28 ± 0.07 vs. 7.06 ± 0.03 m/s, p = .002) than CT heterozygotes and CC homozygotes. There appeared to be a decrease in foot PWV in youth with the 241Arg allele (ICAM1) as compared to those without (6.96 ± 0.08 vs. 7.14 ± 0.03 m/s, p = .005). For the Asp693Asp (C to T) polymorphism (VCAM1), CC genotype had higher foot PWV than CT and TT genotypes (7.18 ± 0.04 vs. 6.95 ± 0.06 m/s, p < .0001). There was an epistatic interaction between Ser290Asn, Gly241Arg, and Asp693Asp on foot PWV (p = .017), explaining 3.6% variance of the foot PWV. Conclusion: Genetic variation of adhesion molecules may be implicated in the development of arterial stiffness. Screening for adhesion molecule polymorphisms may help identify high-risk youth.

We explored heritabilities of the State and Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT), and associations including genetic and environmental correlations between the phenotypes among Korean twins and their families. We analyzed the data of 1,748 participants (835 men, 913 women, 656 individuals of monozygotic twins, 173 individuals of same-sexed dizygotic twins, 919 non-twin family members, age 30–79 years) from the Healthy Twin study. Heritabilities and bivariate analyses were assessed using the SOLAR package software. In the methods of generalized estimation equations, women in the 4th quartile of state and trait scores were 17% and 15%, respectively more likely to be hazardous alcohol users compared to women in the lower three quartiles (P < .05). However, there were no significant associations between these phenotypes in men. After adjusting for age and squared age, the heritability estimates were 0.26 in men and 0.34 in women for the state score; for the trait score, 0.35 in men and 0.31 in women; for the AUDIT score, 0.32 in men and 0.37 in women (P < .001). After adjusting for age and squared age, there was a significant genetic correlation between the trait score and the AUDIT score, and a significant non-genetic correlation between the state score and the AUDIT score in women, while there were no significant genetic or non-genetic correlations between these phenotypes in men. The STAI and AUDIT scores are heritable in Koreans and the relationships between these phenotypes may be inconsistent by sex.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.

We report our experience on the application of Gratacos’ classification in a cohort of monochorionic pregnancies complicated by selective intra-uterine growth retardation based on the Doppler assessment of the umbilical artery. Materials and methods: A retrospective study was conducted on 52 cases of monochorionic twin pregnancies, in which one twin presented an abdominal circumference at or below the 10th percentile for gestational age. Cases were classified into three types according to the umbilical artery Doppler in the smaller twin. Subsequently, patients were divided into two groups: the selective IntraUterine Growth Retardation group and the Twin-to-Twin Transfusion Syndrome (TTTS) group. Results: Of the total 52 cases, 37 were classified as Type I, 12 as Type II, and 3 as Type III cases. In the total group, progressive fetal deterioration of the smaller fetus requiring active management was observed in 66.7% of Type II and 11.1% of Type I cases (p < .001), and in no Type III case. Unexpected fetal death of the smaller twin was observed more frequently in Type III (two cases, 66.7%) than in Types I and II cases (5% and 33%, respectively). Among the 52 cases, TTTS with oligo-polyhydramnios sequence was diagnosed in 10 cases. The remaining 42 cases were therefore defined as selective intra-uterine growth retardation. In the selective IntraUterine Growth Retardation group, results were similar to those obtained for the whole population. Conclusions: Classification of complicated monochorionic twins based on the umbilical artery Doppler is particularly important for counseling, even when we include TTTS cases, and permits the prediction of clinical evolution and perinatal outcome.

This article reports the first behavioral genetic study of relationships between alexithymia and four styles of humor: affiliative, self-enhancing, self-defeating, and aggressive. A total of 509 MZ pairs and 264 DZ pairs of twins completed the Toronto Alexithymia Scale-20 (TAS-20) and the Humor Styles Questionnaire (HSQ). Consistent with our predictions, alexithymia correlated negatively with affiliative and self-enhancing humor and positively with self-defeating and aggressive humor. All but one of the 16 phenotypic correlations that we report are significant at the 0.01 level. Also consistent with our predictions, the phenotypic correlations between alexithymia and humor styles were primarily attributable to correlated genetic factors and to a lesser extent to correlated non-shared environmental factors. Correlated shared environmental factors had no significant effect. Implications and limitations of this study are discussed.

The development of an intracranial aneurysm (IA) is a multifactorial process, involving genetic and environmental factors. The presence of IA or aneurysmal subarachnoid hemorrhage (aSAH) in twins is particularly interesting, since both genetic and environmental factors can be studied. It also raises the question of whether, when one twin is affected, the other asymptomatic twin should be examined for an IA. We report on a monozygotic (MZ) twin-pair with aSAH in both twins and we review all reported cases of IA in MZ twins. Including our case, we found only 14 MZ twin-pairs in which both twins harbored an IA, suggesting a heavy underreporting in the medical literature. In this small group, a high concordance was noted in the sites of IAs. In MZ twins, the preferred sites for IAs are the branching arteries, while aneurysms arising from fusion arteries are rare. These sites differ from the preferential sites seen in series of familial IAs and series of sporadic IAs. We therefore hypothesize that the twinning process might play a significant role in the development of IAs in MZ twins. To further explore and substantiate this, the large twin registries should be studied. Although IAs in MZ twins with a negative family history for IAs should not be regarded as familial IAs, screening of the asymptomatic twin should be seriously considered if one MZ twin presents with an aSAH or an IA, because of the high fatality rates reported in asymptomatic (and not screened) MZ twin-halves.

We used a prospective cohort to analyze the effect of change in BMI rather than change in weight, in mothers carrying dichorionic twins from a population that did not receive any dietary intervention. A total of 269 mothers (150 nulliparas and 119 multiparas) were evaluated. The average change (%) from the pre-gravid BMI was 7.2 ± 6.1, 17.4 ± 8.2, and 28.7 ± 10.8, at 12–14, 22–25, and 30–34 weeks, respectively, without difference between nulliparas and multiparas. The comparison between maternities below or above the average change from the pregravid BMI failed to demonstrate an advantage (in terms of total twin birthweight and gestational age) of an above average change from the pregravid BMI, even when the lower versus upper quartiles were compared. Our observations reached different conclusions regarding the recommended universal dietary intervention in twin gestations. A cautious approach is advocated towards seemingly harmless excess weight gain, as normal weight women may turn overweight, or even obese, by the end of pregnancy, and be exposed to the untoward effects of obesity on future health and body image.

One salient characteristic of twin studies and the related behavioral genetics paradigm is the requirement of a large sample size. Countries or regions that are large in size and highly populated are at an advantage when implementing twin studies. However, given the fascinating and promising results obtained from twin studies, many researchers based in smaller countries or regions may still want to conduct twin studies in order to address local and theoretical issues. In this article, we have outlined the development of twin studies in Hong Kong, one of the Special Administrative Regions of China. The historical development and design of the two major twin studies of language and reading development implemented within Hong Kong are discussed, providing insights to researchers who also aspire to conduct twin studies in small regions.

More than 100 pairs of adult twins, reared apart and growing old separately, have participated in the Japanese Study of Adult Twins Reared Apart and Growing Old Separately since it began in 1974. The subjects are 161 pairs of adult twins born between 1910 and 1945 in Japan. The main focus of this study is to investigate the influences of environmental factors and life history on life satisfaction and psychological well-being in later adulthood. A mail survey has been conducted on these twins each year since 1974. To date, the Wechsler Adult Intelligent Scale, Maudsley Personality Inventory, Newgarten Life Satisfaction Index, comprehensive medical examinations and personal interviews have been conducted for 12 twin pairs residing in various areas of Japan.

When twinning rates are studied, maternal age and parity should be considered. Data on parity are seldom available. We studied information about the mean parity, using the gross reproduction rate, the total fertility rate and the crude birth rate. These are strongly correlated with the mean parity. The crude birth rate is more readily available than the gross reproduction rate or the total fertility rate. Earlier studies have shown that it is difficult to model variations in the twinning rate with data for the macrolevel. In this study these findings are explained by theoretical analyses and illustrated by empirical data. Sweden, having the oldest continuous population statistics and high twinning rates, offers excellent possibilities for analyses of the twinning rate. We considered data for the counties of Gotland, Älvsborg and Stockholm and the city of Stockholm from 1749 to 1960 and for Sweden until 1996. For Älvsborg, the twinning rate was low for the whole period, showing no statistically significant decreasing trend. It is mainly about 11–14 per thousand, which is only 50–60% of the twinning rate in Gotland in the 18th century. In Gotland, in the county of Stockholm, in the city of Stockholm and in Sweden as a whole, the decreasing trends in the twinning rate were statistically significant. The decreasing twinning rates converge towards the low twinning rate of Älvsborg. After standardization of the twinning rate, the differences remained and the low rate in Älvsborg could not be explained by maternal age.

Work incapacity is a major public health challenge and an economic burden to both society and individuals. Understanding the underlying causes is becoming ever more relevant as many countries face an aging workforce. We examined stability and change in genetic and environmental factors influencing work incapacity from age 18 until retirement, and sex differences in these effects. The large population-based sample comprised information from 28,759 twins followed for up to 23 years combined with high-quality national registry data. We measured work incapacity as the total proportion of potential workdays lost due to sickness absence, rehabilitation and disability benefits. Structural equation modeling with twin data indicated moderate genetic influences on work incapacity throughout life in both men and women, with a high degree of genetic stability from young to old adulthood. Environmental influences were mainly age-specific. Our results indicate that largely the same genetic factors influence individual differences in work incapacity throughout young, middle and older adulthood, despite major differences in degree of work incapacity and probable underlying medical causes.

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.

Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.

Reports on the first successful separation of conjoined twins in 1689 and especially the publication of this achievement, as late as 1752, in the Helvetisch-vernünftiche Wehe-Mutter by Johannes Fatio are discussed in this paper with the intention to correct several historical inaccuracies.

Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980–1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

This paper examines the association between individuals' beliefs that the world is a dangerous place and their support for a variety of national security policies. We find that the source of the covariance between perceived danger and support for aggressive national security policies is primarily due to a common genetic factor. Latent genetic factors that influence individuals' perception of danger also appear to influence their positions on policies purported to alleviate such danger. Covariation between individuals' experiences and genes suggests that priming messages alone do not drive the covariation between feelings of danger and acceptance of policy changes.

Binocular rivalry (BR) is an intriguing phenomenon that occurs when two different images are presented, one to each eye, resulting in alternation or rivalry between the percepts. The phenomenon has been studied for nearly 200 years, with renewed and intensive investigation over recent decades. The rate of perceptual switching has long been known to vary widely between individuals but to be relatively stable within individuals. A recent twin study demonstrated that individual variation in BR rate is under substantial genetic control, a finding that also represented the first report, using a large study, of genetic contribution for any post-retinal visual processing phenomenon. The twin study had been prompted by earlier work showing BR rate was slow in the heritable psychiatric condition, bipolar disorder (BD). Together, these studies suggested that slow BR may represent an endophenotype for BD, and heralded the advent of modern clinical and genetic studies of rivalry. This new focus has coincided with rapid advances in 3D display technology, but despite such progress, specific development of technology for rivalry research has been lacking. This review therefore compares different display methods for BR research across several factors, including viewing parameters, image quality, equipment cost, compatibility with other investigative methods, subject group, and sample size, with a focus on requirements specific to large-scale clinical and genetic studies. It is intended to be a resource for investigators new to BR research, such as clinicians and geneticists, and to stimulate the development of 3D display technology for advancing interdisciplinary studies of rivalry.

We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.

We analyzed the characteristics of weight growth and present the weight growth charts from birth to 6 years of age in Japanese triplets. The study included 366 mothers and their 1098 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' weight growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birthweight proved to be the strongest contribution on weight of triplets from 1 to 6 years of age. In addition, gestational age was also a significant contributing factor to weight from birth to 6 years of age. Moreover, males had a higher weight from birth to 6 years of age than females. Compared to the 50th percentile of the growth standard for the general population of Japan, the weight deficit of the triplets was more than 40% at birth (male, –1.28 kg; female, –1.28 kg), decreased within the first 1 year of age, and fluctuated between 4% and 9% until 6 years of age (male, –1.82 kg; female, –1.78 kg). In conclusion, triplets have lower birth weight than singletons and in spite of the rapid catch-up growth during first year of life they are behind singletons even in mid-childhood. This study provides growth curves for use in triplets.