The disease- and mortality-related difference between biological age based on DNA methylation and chronological age (Δage) has been found to have approximately 40% heritability by assuming that the familial correlation is only explained by additive genetic factors. We calculated two different Δage measures for 132 middle-aged female twin pairs (66 monozygotic and 66 dizygotic twin pairs) and their 215 sisters using DNA methylation data measured by the Infinium HumanMethylation450 BeadChip arrays. For each Δage measure, and their combined measure, we estimated the familial correlation for MZ, DZ and sibling pairs using the multivariate normal model for pedigree analysis. We also pooled our estimates with those from a former study to estimate weighted average correlations. For both Δage measures, there was familial correlation that varied across different types of relatives. No evidence of a difference was found between the MZ and DZ pair correlations, or between the DZ and sibling pair correlations. The only difference was between the MZ and sibling pair correlations (p < .01), and there was marginal evidence that the MZ pair correlation was greater than twice the sibling pair correlation (p < .08). For weighted average correlation, there was evidence that the MZ pair correlation was greater than the DZ pair correlation (p < .03), and marginally greater than twice the sibling pair correlation (p < .08). The varied familial correlation of Δage is not explained by additive genetic factors alone, implying the existence of shared non-genetic factors explaining variation in Δage for middle-aged women.

Gene-based tests such as versatile gene-based association study (VEGAS) are commonly used following per-single nucleotide polymorphism (SNP) GWAS (genome-wide association studies) analysis. Two limitations of VEGAS were that the HapMap2 reference set was used to model the correlation between SNPs and only autosomal genes were considered. HapMap2 has now been superseded by the 1,000 Genomes reference set, and whereas early GWASs frequently ignored the X chromosome, it is now commonly included. Here we have developed VEGAS2, an extension that uses 1,000 Genomes data to model SNP correlations across the autosomes and chromosome X. VEGAS2 allows greater flexibility when defining gene boundaries. VEGAS2 offers both a user-friendly, web-based front end and a command line Linux version. The online version of VEGAS2 can be accessed through https://vegas2.qimrberghofer.edu.au/. The command line version can be downloaded from https://vegas2.qimrberghofer.edu.au/zVEGAS2offline.tgz. The command line version is developed in Perl, R and shell scripting languages; source code is available for further development.

Male twin gestations exhibit higher incidence of fetal morbidity and mortality than singleton gestations. From an evolutionary perspective, the relatively high rates of infant and child mortality among male twins born into threatening environments reduce the fitness of these gestations, making them more vulnerable to fetal loss. Women do not perceive choosing to spontaneously abort gestations although the outcome may result from estimates, made without awareness, of the risks of continuing a pregnancy. Here, we examine whether the non-conscious decisional biology of gestation can be linked to conscious risk aversion. We test this speculation by measuring the association between household surveys in Sweden that gauge financial risk aversion in the population and the frequency of twins among live male births. We used time-series regression methods to estimate our suspected associations and Box–Jenkins modeling to ensure that autocorrelation did not confound the estimation or reduce its efficiency. We found, consistent with theory, that financial risk aversion in the population correlates inversely with the odds of a twin among Swedish males born two months later. The odds of a twin among males fell by approximately 3.5% two months after unexpectedly great risk aversion in the population. This work implies that shocks that affect population risk aversion carry implications for fetal loss in vulnerable twin pregnancies.

Background: Hypospadias is associated with twinning. The incidence of hypospadias in monochorionic and dichorionic male twins is, however, yet to be determined. Methods: All medical records of monochorionic and dichorionic twins admitted to our neonatal nursery between January 2004 and August 2013 were reviewed for the presence of hypospadias. Results: A total of 350 monochorionic and 303 dichorionic male twins were included in the study. The incidence of hypospadias in monochorionic and dichorionic groups was 4% (14/350) and 1% (3/303) (p = .016) respectively. In 11 of the 15 twin couples, hypospadias occurred in the twin with the lowest birth weight. The rate of hypospadias in twin infants small-for-gestational-age group was 10% (6/60) compared with 2% (11/593) in the appropriate-for-gestational-age group (p = .002). In a multivariate analysis, both monochorionicity and small-for-gestational-age were independently associated with hypospadias, odds ratio 4.1 (95% confidence interval (CI): 1.1–14.7) and 6.1 (95% CI: 2.2–17.2) respectively. Conclusions: The incidence of hypospadias is four-fold higher in monochorionic twins compared with dichorionic twins. Hypospadias is also independently associated with small-for-gestational-age.

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Given the uniqueness of the Hungarian conjoined twin sisters Helen and Judith (1701–1723) and their lasting influence as an anatomical showcase if not model for mental or social deviant states, we present here a closer scrutiny of their introduction into the scientific literature of the later 18th century by analyzing depictions of the twins from 1707 onwards.

A single umbilical artery (SUA) was identified in 1.5% of twin pregnancies. The presence of a SUA in a twin pregnancy was associated with a 50% incidence of fetal anomalies, many of them complex and severe. The embryology and pathophysiological mechanisms associated with a SUA are reviewed. Aneuploidy is relatively common and should be considered, particularly in the presence of associated anomalies. Fetal growth restriction is frequent and preterm delivery is common.

Twins reared apart provide a fascinating experiment to distinguish genetic from environmental influences. However, there is as yet no broad report on distribution of twins reared apart, especially in the Chinese population. In this study, information on 18,295 volunteer twin pairs of all age groups was compiled in nine provinces or cities of China, and questionnaires were used for zygosity determination. It was discovered that twins reared apart from 0 to 10 years of age accounted for 2.2% of all twin interviewees, with the proportion of this 0–10 group separated before 1, 2, and 5 years old, accounting for 65.3%, 76.1%, and 91.3%, respectively. The proportion of twins reared apart is not significantly related to zygosity or gender, but it is related to region and twin age. As the age of twins lowers, the proportion of those reared apart gradually decreases. Twins reared apart will become rarer in the future and therefore should be cherished as a resource.

Neurophysiological measurements of the response to pre-pulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic pre-pulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study, we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18–30 years) MA men (n = 170), and women (n = 250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to pre-pulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the pre-pulse/startle response in this cohort.

We analyzed the effect of total fertility rate (TFR) and crude birth rate (CBR) on the number of males per 100 females at birth, also called the secondary sex ratio (SR), and on the twinning rate (TWR). Earlier studies have noted regional variations in TWR and racial differences in the SR. Statistical analyses have shown that comparisons between SRs demand large data sets because random fluctuations in moderate data are marked. Consequently, reliable results presuppose national birth data. Here, we analyzed historical demographic data and their regional variations between counties in Sweden. We built spatial models for the TFR in 1860 and the CBR in 1751–1870, and as regressors we used geographical coordinates for the provincial capitals of the counties. For both variables, we obtained significant spatial variations, albeit of different patterns and power. The SR among the live-born in 1749–1869 and the TWR in 1751–1860 showed slight spatial variations. The influence of CBR and TFR on the SR and TWR was examined and statistical significant effects were found.

Many triplets are conceived as a consequence of assisted reproductive technology (ART). Concerns have been raised that triplet pregnancies conceived by ART are more complicated than those conceived spontaneously. The purpose of this study was to evaluate all triplet pregnancies managed over a 12-year period to determine if there were any differences in outcome based on the mode of conception. All triplet pregnancies between 1999 and 2011 that reached at least 20 weeks’ gestation and that were managed at the Royal Women's Hospital (RWH), Melbourne, Victoria were identified. Maternal and neonatal outcomes were compared between ART conceived and spontaneously conceived triplets. In the study period, 53 sets of triplets managed in our institution met the eligibility criteria. Twenty-five triplet sets were conceived by ART and 28 were conceived spontaneously. More ART conceptions resulted in trichorionic triamniotic (TCTA) triplets than did spontaneous conceptions (p = .015). There were no differences between ART and spontaneously conceived triplets for any of the maternal or neonatal complications studied. Trichorionic (TC) triplets delivered at a later gestation than other triplets: 32.1 (SD 2.9) versus 30.4 (SD 3.9) weeks (p = .08). TC triplets were significantly less likely to die than monochorionic (MC) or dichorionic (DC) triplets: 3/93 (3%) versus 13/66 (20%) (p = .025). In conclusion, triplets conceived by ART are more likely to have TCTA placentation and TCTA triplet sets had lower mortality rates than other triplet combinations. Outcomes for triplets conceived by ART were similar to those of triplets conceived spontaneously.

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.

Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115–8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.

The centenary celebration for Scottish missionary, Mary Slessor, took place on February 14, 2015 in Melle, Belgium. Slessor saved many newborn twins and their mothers from death and disownment by members of their community, including their families, who believed twins harbored evil spirits. The events of this unusual and significant gathering are described. Next, twin research and reports concerning Kleinfelter's disease, atopic diseases, autism and psychotherapy are presented. General interest subjects include identical female twin pole-vaulters, the longest twin birth interval, Franco-Cuban twin vocalists, and Croatian twin models.

The study endeavored to assess the epidemiology, postnatal survival, and growth pattern of multiple births in Sub-Saharan Africa (SSA). It was based on the data of 25 demographic health surveys conducted in the subcontinent since 2008. The records of 213,889 children born in the preceding 59 months of the surveys were included. The multiple birth rate was computed as the number of multiple confinements per 1,000 births. Factors associated with multiple births were identified using logistic regression and their survival pattern was assessed using the Kaplan–Meier method. The multiple birth rate was 17.1 (95% confidence interval: 17.7–16.6) and showed considerable variation across the 25 countries included in the study. Odds of multiple births were significantly increased with advanced maternal age, parity, and maternal height but not with wealth index, age at first birth, and month of birth. At the end of the fourth year of age, the cumulative survival probability was as low as 0.77 in multiple births as compared to 0.93 in their counterparts. The odds of neonatal, infant and under-five mortality were 5.55, 4.39, and 3.72 times increased in multiple births, respectively. Multiple births tend to be malnourished than singletons and the odds of wasting, stunting, and underweight were 1.31, 1.83, and 1.73 times raised, consecutively. Nevertheless, multiple births regain their weight-for-age (WFA) and height-for-age (HFA) deficits by the end of the fourth year of age. Counseling pregnant mothers with multiple gestation to give birth at a health institution and providing close medical follow-up during and after the neonatal period can improve the survival of multiple births.

Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16–19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor.

Longitudinal studies of neuroticism have shown that, on average, neuroticism scores decrease from adolescence to adulthood. The heritability of neuroticism is estimated between 0.30 and 0.60 and does not seem to vary greatly as a function of age. Shared environmental effects are rarely reported. Less is known about the role of genetic and environmental influences on the rank order stability of neuroticism in the period from adolescence to adulthood. We studied the stability of neuroticism in a cohort sequential (classical) twin design, from adolescence (age 14 years) to young adulthood (age 32 years). A genetic simplex model that was fitted to the longitudinal neuroticism data showed that the genetic stability of neuroticism was relatively high (genetic correlations between adjacent age bins >0.9), and increased from adolescence to adulthood. Environmental stability was appreciably lower (environmental correlations between adjacent age bins were between 0.3 and 0.6). This low stability was largely due to age-specific environmental variance, which was dominated by measurement error. This attenuated the age-to-age environmental correlations. We constructed an environmental covariance matrix corrected for this error, under the strong assumption that all age-specific environmental variance is error variance. The environmental (co)variance matrix corrected for attenuation revealed highly stable environmental influences on neuroticism (correlations between adjacent age bins were between 0.7 and 0.9). Our results indicate that both genetic and environmental influences have enduring effects on individual differences in neuroticism.