Background: Recent studies have suggested that ovarian stimulation and assisted reproductive techniques (ART) may increase the frequency of monozygotic twins. In this article, we present the analysis of the estimated frequency of twin deliveries following in vitro fertilization (IVF) in Lombardy during the period 2010–2014 for a total of 450,949 pregnancies. Method: This is a population-based study using data from the regional data base of Lombardy, a northern Italian region with a population of about 10 million inhabitants. During the considered period, a total of 461,424 single or multiple births were registered in Lombardy. After exclusion of triplets or more pregnancies, the total number of twin deliveries, in separate strata of like and unlike sex pregnancies twin deliveries, were obtained and the rate of twin deliveries was computed according to spontaneous and non-spontaneous conception and type of ART. Further, estimates of dizygotic or monozygotic twin births were calculated using Weinberg's methods. Results: The frequency of twins deliveries was 1.24/100 deliveries after natural conception and 20.05 after assisted conception. The estimated rates of monozygotic twins was 0.45 and 0.72/100 (95% CI: 0.58–0.91) deliveries after natural and assisted conception, respectively. This difference was statistically significant (p < .05). Conclusion: the present population based study suggests that the risk of monozygotic twin is about 60% higher among assisted than after natural conception.

Background: The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors. Method: The aim of this study was to estimate genetic and environmental influences on basal cortisol levels in a sample of 151 twin pairs aged 9–16 years. Salivary cortisol was collected on two consecutive days when the children attended school — immediately after awakening, 30 min post-awakening and at bedtime. Results: Heritability was highest (60%) for cortisol levels about 30 min after awakening. For samples taken immediately at awakening heritability was less pronounced (28%) and in the evening low (8%). Conclusion: The limited genetic influence on evening levels, moderate on cortisol at awakening and high on awakening response, might imply two genetic regulation patterns, one specifically for awakening response and one for the circadian rhythm proper. These findings could explain divergent results in previous studies and highlight the importance of taking the circadian rhythm into account in studies of cortisol levels in children.

Perinatal mortality rates (PMRs) in triplets were analyzed using Japanese Vital Statistics during the period of 1980–1998. The total number of perinatal deaths in triplets was 1051. The PMR significantly decreased from 214 per 1000 births in 1980 to 39 in 1998, a reduction of 82%. PMRs in triplets were 11.1-fold higher in 1980 and 6.9-fold higher in 1998 than in singletons, indicating that PMRs improved more in triplets than in singletons during the last two decades in Japan. The PMR was the highest in the third-born, followed by the second- and the first-born triplets in each period. As for maternal age, the PMR was 1.5–3.7 times higher in the < 25 years of age group than the other age groups. Additionally, the PMR was the lowest for birthweight (BW) ≥ 2000g during the entire period. In addition, the PMR decreased with gestational age (GA) of up to 38–39 weeks and increased thereafter. The effects of BW on the PMR were stronger than the effects of GA. The proportion of perinatal deaths in triplets with extremely low BW (< 1000g) was 74% in 1980–1989 and increased to 82% in 1990–1998. The declining PMR was unlikely to be due to the improvement in BW in triplets. It is likely that it was related to the improved medical management of triplets during the perinatal period and the first week of life. Information obtained in the present study may be useful in counseling pregnant woman about triplet births.

Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue are conditions of unknown etiology. The Centers for Disease Control and Prevention (CDC) define CFS as an illness characterized by ≥ 6 months of disabling fatigue associated with muscle pain, pharyngitis, and alterations in mood, sleep and neurocognition. We constructed a registry of twins with chronic fatigue to facilitate research on the impact of illness, the associated medical and psychosocial factors, and the heterogeneous proposed mechanisms for these conditions. We have recruited 204 twin pairs in which one or both members reported persistent fatigue through patient support group newsletters (60%), clinicians/researchers familiar with CFS (12%), notices placed on electronic bulletin boards for CFS (11%), twin organizations and researchers (6%), relatives and friends (3%) and other sources (8%). Complete data are available for 177 pairs (87%). Twins completed an extensive questionnaire booklet that included measures of physical and mental health, functional status, and psychosocial factors; a structured psychiatric interview was also conducted by telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic fatigue: 1) ≥ 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured interview (69 discordant pairs and 25 concordant pairs). Despite the limitations of a volunteer registry, the Chronic Fatigue Twin Registry promises to be an important resource for research on CFS and chronic fatigue.

Specific environments and social relationships may alter the impact of genes. Previous studies have shown marriage to moderate heritability for depressive symptoms in females, suggesting that marriage provides protection or compensation against genetic risks. Similar mechanisms may be relevant for subjective wellbeing (SWB), which is considerably influenced by genes and almost universally associated with marital status. Questionnaire data on SWB from a population-based sample of 1250 monozygotic (MZ) and 981 dizygotic (DZ) male and female twin pairs (n = 4462) were analyzed using structural equation modeling by means of Mx to investigate genetic and environmental influences on SWB across marital status. Resemblance for SWB in MZ twins exceeded that of DZ twins, but the magnitude of this difference varied across marital status. Genetic factors explained 51% and 54% of the variance in SWB among unmarried males and females, and 41% and 39% in married or cohabitating respondents. Remaining variance was attributable to the nonshared environment. The genetic influences were partly different (rg = 0.64) across marital status in females, but overlapping in married and single males. Our findings show that marriage moderates the magnitude of genetic influences on SWB in both males and females, with a smaller estimate of genetic influences for those with a marital or equivalent partner. The genetic influences on SWB are thus clearly contingent on the environmental context.

The Norwegian Institute of Public Health in Oslo has an ongoing program of twin research using population-based cohorts of twins. The current database includes information on twins identified through the Medical Birth Registry of Norway and born from 1967–1979, altogether 15,370 twins. This is a longitudinal study with a cohort sequential design whereby new cohorts are recruited into the study at 5–6 year intervals. Sub-samples of these twins have participated in questionnaire studies and clinical assessment sub-projects. These projects include national and international collaborations. Our primary areas of interest include mental health and psychological well-being, obesity, asthma and allergies, health behaviors and health perceptions, comorbidity, and perinatal influences on health outcomes. This paper provides a brief overview of the data, sample, and the various research projects associated with this twin program of research.

There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on these pathways, in three different ways. First, in a twin pregnancy maternal nutritional resources and the “supply line” to the fetuses will be more “stretched”. We hypothesise that study of twin pregnancies is a more efficient way to identify modifiable maternal factors that influence later health than studies of singleton pregnancies. Second, twins have lower birthweight than singletons. Comparison of cardiovascular disease risk in twins versus that in singletons will provide insight into whether birthweight per se is in the underlying causal pathway of interest, and whether factors constraining fetal growth of twins (versus singletons) affect later outcome. Third, twin cohorts provide an opportunity to investigate the role of “shared” factors versus factors affecting each individual fetus, by comparing results of within-cohort versus within-pair analyses. Generalisability of findings in twins is debated. We suggest that findings in monochorionic twins (or in the absence of chorionicity data, those from monozygotic twins) need to be interpreted with caution.

Early loss of one fetus in a multiple gestation as a ‘vanishing’ twin is a well recognized phenomenon. It is uncertain whether this has an impact on the development of the surviving co-twin. The aim of this study is to compare the development of singletons, twins and the surviving co-twins of a vanishing twin. The 324 children born to 229 women who were recruited into the study between 1999 and 2001 formed the study population. Children were assessed at 1 year of age with Griffiths Mental and Developmental Scales. A neurological examination was performed using an optimality score to exclude those with severe neurodisability. Three hundred and five children (92 singletons, 180 twins and 33 survivors with a vanishing twin) were included. The sub- and general quotient scores in singletons and surviving co-twins of a vanishing twin did not differ significantly. Twins had significantly lower scores than singletons in all areas of development and were more likely to be born early with lower birthweights. Following adjustment for gestation and birthweight, the difference between the two groups was nullified suggesting that the slower development of twins is related to their prematurity and lower birthweight.

The present study examined the effects of chorionicity of twins on variations of height, weight, and body mass index (BMI) during childhood in the classical twin design. Mothers of 81 pairs of monochorionic monozygotic (MCMZ), 47 pairs of dichorionic monozygotic (DCMZ), and 457 pairs of dizygotic (DZ) twins drawn from the South Korean Twin Registry reported their children's height and weight. Twins' age ranged from 1.9 to 8.7 yrs, with a mean of 4.0 yrs and SD of 1.7 yrs. We computed maximum likelihood twin correlations and performed model-fitting analyses. In correlational and model-fitting analyses, we treated age and sex as covariates to control their main effects. Maximum likelihood MCMZ, DCMZ, and DZ twin correlations were, respectively, .96, .92, and .74, for height, .88, .91, and .57 for weight, and .93, .92, and .61 for BMI. The pattern of these twin correlations suggested very modest chorion effects on body measures. Model-fitting analyses confirmed the observations from twin correlations. Whereas genetic and shared environmental influences were significant for all three body measures, chorion effects attained statistical significance only for height (4%), and those for weight and BMI were zero. These findings indicate that genetic and environmental estimates for height, weight, and BMI during childhood are biased little by the chorion type of MZ twins, supporting the validity of the equal prenatal environment assumption in the classical twin design.

Mexican Americans (MAs) and American Indians (AIs) constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the MA cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the AI sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

The present study is the first to examine relationships between alexithymia and trait emotional intelligence (trait EI or trait emotional self-efficacy) at the phenotypic, genetic, and environmental levels. The study was also conducted to resolve inconsistencies in previous twin studies that have provided estimates of the extent to which genetic and environmental factors contribute to individual differences in alexithymia. Participants were 216 monozygotic and 45 dizygotic same-sex twin pairs who completed the Toronto Alexithymia Scale-20. In a pilot study, a sub-sample of 118 MZ and 27 DZ pairs also completed the Trait Emotional Intelligence Questionnaire. Results demonstrated that a combination of genetic and non-shared environmental influences contribute to individual differences in alexithymia. As expected, alexithymia and trait EI were negatively correlated at the phenotypic level. Bivariate behavioral genetic analyses showed that that all but one of these correlations was primarily attributable to correlated genetic factors and secondarily to correlated non-shared environmental factors.

The aim of this study was to determine the influence of genetic factors on the first episode of acute myocardial infarction. Probandwise concordances, tetrachoric correlations and quantitative genetic analyses of liability were applied to data drawn from the Swedish Twin Registry and the Swedish Acute Myocardial Infarction Register. All same-sexed twin pairs born between 1886 and 1958 who were alive in 1987 were included in the analyses. Our results show that concordance rates for acute myocardial infarction in monozygotic (MZ) twins were similar across sexes (among males .26 and females .27). For dizygotic (DZ) twins the concordances were .20 for males and .16 for females, yielding a greater MZ–DZ concordance differential for females than males. Tetrachoric correlations were greater for MZ than DZ twins for both sexes (.49 for male MZ and .34 for male DZ-twins and .56 and .35 for female MZ and DZ twins respectively). Quantitative genetic analyses of liability resulted in equal variance components for males and females (.36) but significantly different thresholds (prevalences). In conclusion, liability to first occurrence of acute myocardial infarction is moderately influenced by genetic variants in both sexes. The familial influence on phenotypic variance is exclusively explained by additive genetic factors.

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of twin pairs ascertained from birth records and school system records of Virginia, North Carolina, and South Carolina. The MATR was formed in 1997 with the merging of the Virginia and North Carolina Twin Registries, and it expanded to include South Carolina when access to twin birth records in that state was granted in 1998. Registered twins (“participants”) number more than 51,000, with approximately 46,000 of these individuals representing complete pairs. Roughly two-thirds of MATR participants are over age 18, with a mean age of approximately 35 years. These participants have primarily been drawn from the more than 170,000 identical and fraternal twin pairs born in the three states between 1913 and 2000. Twins and their family members have participated in numerous research projects, ranging from general health surveys to studies on specific health topics such as cardiovascular disease; depression and anxiety; seizures; behavioral development; pregnancy complications; conduct disorder; drug use, abuse, and dependence; cleft lip/palate; obesity; and chronic fatigue syndrome. The MATR has established a privacy policy and strict standard operating procedures to protect the confidentiality of participant data. The MATR considers a limited number of qualified requests per year from investigators interested in recruiting MATR participants into their research studies.

Although it has been suggested that genetic influences on reading difficulties may differ in boys and girls, results obtained from previous analyses of data from same-sex twin pairs have failed to provide evidence for a differential genetic etiology of reading disability (RD) as a function of gender. However, results of a recent study in which data from both same-sex and opposite-sex twin pairs were analyzed indicated a higher heritability for reading difficulties in boys (Harlaar et al., 2005). Because the current sample of twin pairs tested in the Colorado Learning Disabilities Research Center is substantially larger than that analyzed for our previous report (Wadsworth et al., 2000), this hypothesis was tested more rigorously using data from both same-sex and opposite-sex twin pairs in our current augmented sample. Composite reading scores from 634 twin pairs were subjected to DeFries–Fulker sex-limitation analysis using the model-fitting approach of Purcell and Sham (2003). Analysis of data from the combined sample of male and female twins indicated that genetic influences account for more than half the proband reading deficit (h2g = .58). When this model was extended to test for gender differences in the magnitude of genetic influences on RD, h2g estimates were somewhat higher for females than for males (.63 and .53, respectively), but the difference was nonsignificant (p > .3). A test for qualitative gender differences was also nonsignificant. Thus, these results provide little evidence for a differential genetic etiology of RD in boys and girls.

The effect of assisted reproductive technology (ART) and non-ART ovulation stimulation fertility treatment on the number and rate of multiple live births from 1979–2008 in Japan was estimated using two independent data sources, ART statistics and vital statistics. Japanese ART statistics presented by the Japan Society of Obstetrics and Gynecology between 1989 and 2008 were gathered and reanalyzed. The number and rates of ART between 1984 and 1988 were interpolated using an approximation formula, using the values from 1983, when the first ART baby was born in Japan, and the 1989–1992 values. The number of ART multiples between 1979–1982 was set as equal to zero. The minimum (or maximum) number of non-ART iatrogenic multiple births was estimated by subtracting the maximum (or minimum) ART multiples from the total iatrogenic multiples, which was estimated by vital statistics assuming that spontaneous multiple-birth rates according to maternal age class would be constant. There was an overall increase in the non-ART multiple births during the 30-year period, whereas ART multiples tended to increase from 1983 to 2005, and then rapidly decreased thereafter. The number or percentage of ART multiples was almost consistently lower than that of non-ART multiples. The percentage of non-ART multiples (33%) among the total multiples was estimated to be about three times more than the ART multiples (11–12%) in 2008. Given the medical and social impact of multiple births, it is imperative to construct a hospital-based monitoring system for fertility treatments, specially non-ART fertility treatments and multiple births.

Outcomes of multifetal pregnancy in prenatal life are markedly affected by chorionicity. Several disease processes are found in monochorionic (MC) twins that do not occur in dichorionic (DC) twins. Improvements in prenatal outcomes will depend on reliable first trimester diagnosis of chorionicity, allowing early monitoring for complications of MC placentation. Particular structures and functions of MC twin placentas affect outcomes and can be targeted for specific treatments, especially in twin-twin transfusion. The causes of severe DC twin fetal growth discordance are clarified. In post-natal life, zygosity is a determining effect in genetic predisposition to many chronic diseases, including neoplasia. Few MC twins know that they are monozygotic (MZ). Few twin researchers realize that MZ twins may be genetically discordant. Abandonment of the word “identical” for MZ twins would assist in clarifying these issues of zygosity, concordance and discordance.

Twin studies have seldom addressed ethnicity as one of the possible factors that create unique combinations of genetic and environmental influences. The major objective of the Carolina African American Twin Study of Aging is to identify the proportion of the genetic and environmental sources of individual variation in measures of health and behavioral factors in a sample of adult African Americans. Drawn from birth records from the State of North Carolina, this in-person study used public records to identify a cohort of twins between 22 and 92 years of age (X = 49.82 yrs, SD = 14.62), 39.7% of which were men. Members of non-intact twin pairs and siblings were also recruited to explore alternative models to the classic twin design. To date, the project has contributed to knowledge about blood pressure, forced expiratory volume, chronic illness, body mass index, and waist-hip ratio memory, personality, social, and demographic factors, mortality, and mental health.

All etiological studies of complex human traits focus on analyzing the causes of variation. Given this complexity, there is a premium on studying those processes that mediate between gene products and cellular or organismal phenotypes. Studies of levels of gene expression could offer insight into these processes and are likely to be especially useful to the extent that the major sources of their variation are known in normal tissues. The classical study of monozygotic (MZ) and dizygotic (DZ) twins was employed to partition the genetic and environmental influences in gene expression for over 6500 human genes measured using microarrays from lymphoblastoid cell lines. Our results indicate that mean expression levels are correlated about .3 in monozygotic (MZ) and .0 in dizygotic (DZ) twins suggesting an overall epistatic regulation of gene expression. Furthermore, the functions of several of the genes whose expression was most affected by environmental effects, after correction for measurement error, were consistent with their known role in mediating sensitivity to environmental influences.

Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent–offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent–offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research.