This paper describes the creation of a unique maternal identifier for use in the investigation of perinatal, postneonatal and child outcomes in relation to maternal characteristics. All Midwives’ records of Western Australian (WA) births were routinely linked to registrations of births and deaths for infants born from 1980 to 1992 inclusive, then linked to WA hospital discharge data and to registries of birth defects and cerebral palsy to create a longitudinal health record for each infant. However, since each birth to a woman was recorded as a separate event, there was no way to identify siblings. Probabilistic record linkage, based on information about the mother, was used for this task. Logical inconsistencies within the data were used to test the validity of the linkages between birth records attributed to each mother. Information about the mother from other epidemiological studies and data abstracted from hospital case notes was also used to validate sibships. Linkage of the records of 310,255 births in WA during that period resulted in the formation of 181,133 sibships of one or more children. Pooling the results of all of the validation methods gave an error of 0.9%. Linkage identified 3678 sibships containing multiple births, and 305 sets of maternal twins. Ascertainment of twins and their siblings for an ongoing twin register, the WA Twin Child Health (WATCH) study, was a natural consequence of this process.

Empathy plays a central role in prosocial behavior and human cooperation. Very few twin researchers have investigated innate and environmental effects in adult empathy, and twin research on gender differences in these effects is sparse. The goal of this study was to examine innate and environmental influences on three components of an empathy scale frequently used with adults — the expression of cognitive (CE), emotional (EE), and social skills (SS) empathy — and to explore gender differences in the influences. Study participants were ~1,700 twins (18–65 years) enrolled in the Italian Twin Registry. Empathy was assessed with the Italian version of the Empathy Quotient (EQ), for which the three-factor structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic and dizygotic pairs, and males and females were estimated for the total EQ and subscale scores, and univariate genetic model fitting was carried out. Women's empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly driven by genetic factors and individual experiences, whereas for males, no genetic contribution or important shared and individual environmental effects emerged. Although of large magnitude, the gender differences did not reach statistical significance. Age did not moderate empathy heritability in adulthood. Only for the SS subscale were genetic and environmental proportions of variance similar for men and women. This study suggests possible gender-specific innate and environmental influences on empathy and its cognitive and emotional components that need to be confirmed in future studies.

The purpose of this study was to clarify the genetic contribution to finger-sucking and nail- biting in childhood using the largest databases available on Japanese twins. The subjects were 1131 pairs of 12-year-old twin children, consisting of 1057 males and 1205 females. All data were gathered by maternal questionnaire, and responses to the questionnaire were checked in the medical interview. The prevalence of finger-sucking between 0 to 2 years was 40% in males and 43% in females (p = .0053). The prevalence of nail-biting up until the age of 12 years was 28% in males and 26% in females (nonsignificant). Concordance rates and polychoric correlations were all higher in monozygotic pairs than in dizygotic pairs, irrespective of the sex combination. Univariate and bivariate genetic analyses using structural equation modeling was performed. The results showed that the proportion of total phenotypic variance attributable to genetic influences was 66% in males and 50% in females for finger-sucking, and 50% in both males and females for nail-biting. A co-occurrence of finger-sucking and nail-biting was observed in 17.7% of males (tetrachoric correlation: r = .40) and 15.7% of females (r = .32), which was attributed partly to common genetic or environmental factors. The proportion of total shared variance explained by genetic factors was 67%.

The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.

Previous studies indicate that the emotional quality of marital relationships is mirrored in parent–child relationships. We explored the degree to which these associations are explained by genetic and environmental factors. Participants were drawn from the Twin and Offspring Study in Sweden (TOSS), and included 544 female twin pairs (258 monozygotic [MZ], 286 dizygotic [DZ]), and 311 male twin pairs (128 MZ, 183 DZ). The spouses and one adolescent child of each twin also participated in this study. The twins completed self-report measures that assessed their marital quality and their warmth and negativity towards their children. Observational ratings of marital warmth and negativity, and of maternal warmth and negativity were obtained for a subset of female twin pairs (150 MZ, 176 DZ). Selfreported marital satisfaction was associated with self-reported parental warmth and negativity for mothers (rs = .25, -.36) and fathers (rs = .25, -.44). For the observational measures, marital warmth was associated with maternal warmth (r = .42), while marital negativity was associated with maternal negativity (r = .34). On average genetic factors explained nearly half of the covariance between selfreported marital satisfaction and parenting for mothers (48%) and fathers (47%). Genetic factors explained 21% of the covariance between observed marital and maternal warmth, but did not contribute to associations between marital and maternal negativity. These findings indicate that parents' genetically influenced characteristics help shape the emotional climate of the family.

With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individuals age. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP) micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data). Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (R2 > 99%) between co-twins from 43 MZ pairs. For 75 dizygotic (DZ) pairs, R2 was ≈65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (R2 ≈ 90%) and duplications (R2 ≈ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (R2 ≈ 50–60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.

The study of twins and their families provides a highly useful tool for disentangling the genetic and environmental origins of traits. The Cardiff Study of All Wales and North West of England Twins (CaStANET) has followed children and adolescents over time into early adulthood, assessing a wide range of aspects of behavior and psychopathology using self-, parent and teacher reports. Four main waves of data collection have taken place to date, which have provided a wealth of information on the contributions of genetic and environmental risk factors to the psychological health of young people. This article first describes the CaStANET register and subsequently presents some of the findings that have emerged from this resource, with a focus on depression and anxiety, chronic fatigue, attention-deficit/hyperactivity disorder, conduct problems and prosocial behavior. We describe in somewhat more detail the 4th wave of data collection, which has recently been completed and has provided us with extensive information on substance use and problem use as well as associated risk factors in the twins and their families, including longitudinal data on conduct problems and the relations between family members. Because of the wealth of data already collected and the opportunity for genetically informative analyses over time, CaStANET provides a valuable resource for understanding the complexities of the psychological development of young people.

Since established in 1998, the Keio Twin Project (KTP) has been dedicated to investigating genetic and environmental sources contributing to human psychological traits in adolescence and young adulthood. A population-based twin registry was constructed by the KTP through the use of official residential records in the Tokyo area, and to date requests to participate in our research have generated 1040 pairs of twins and triplets of age 14 to 30, forming one of the largest twin registries in Asia. Our comprehensive datasets, obtained through questionnaires, performance tests, and physical measurements, cover a wide range of human traits: personality, psychiatry, mental health, sociality, cognition, and physical index. Demographic variables and environment of upbringing are also sought by twins and by some parents. This extensive information allows us to clarify the genetic and environmental overlap across multiple traits as well as specificities unique to single traits. Adding an evolutionary psychology perspective to the behavior genetics framework is currently being attempted in order to develop a grand theory of human genetics.

Attitudes towards foreign policy have typically been explained by ideological and demographic factors. We approach this study from a different perspective and ex amine the extent to which foreign policy preferences correspond to genetic variation. Using data from the Minnesota Twin Family Study, we show that a moderate share of individual differences in the degree to which one's foreign policy preferences are hawkish or dovish can be attributed to genetic variation. We also show, based on a bivariate twin model, that foreign policy preferences share a common genetic source of variation with political ideology. This result presents the possibility that ideology may be the causal pathway through which genes affect foreign policy preferences.

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin–twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia–polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

We enrolled more than 3500 same-sex twins from 5 consecutive Finnish birth cohorts into a longitudinal study as each cohort reached age 16. Twins completed the Psychopathic Deviate (Pd) Scale of the Minnesota Multiphasic Personality Inventory at baseline, Sensation Seeking Scale items as each cohort reached age 17, and later, at average ages 18.5 and 25, the Rutgers Alcohol Problem Index (RAPI). Using raw maximum likelihood estimation, we fit a Cholesky model to the 4 variables assessed at 4 ages across the 4 twin types; we estimated genetic and environmental influences on the stability of alcohol problems across development and the genetic and environmental contributions to predictive correlations between adolescent personality and later alcohol-related behavior problems. With one exception, the phenotypic, genetic, and environmental correlations were very similar for males and females. The exception was that the lagged associations of Pd and RAPI reflect a higher genetic correlation among males than females and a higher environmental correlation among females than males. Our analyses suggest that developmental changes underlying variation in alcohol problems from late adolescence to early adulthood differ for males and females. In males, the main change is decreased variation due to shared environmental effects; the magnitude of genetic effects is stable over time, and the high genetic correlation, .95, suggests that the same genetic influences are important at both ages. Among females, in contrast, genetic influences decline in magnitude from age 18 to 25, and at least part of the genetic effect evident at age 25 differs from the genetic effect evident at age 18.

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.

There is a lack of evidence pointing to specific dietary elements related to weight gain and obesity prevention in childhood and adulthood. Dietary intake and obesity are both inherited and culturally transmitted, but most prospective studies on the association between diet and weight status do not take genetics into consideration. The objective of this study was to document the association between dietary intake at 9 years and subsequent Body Mass Index (BMI) in adolescent monozygotic boy and girl twin pairs. This research used data from 152 twin pairs. Dietary data were collected from two 24-hour-recall interviews with a parent and the child aged 9 years. Height and weight were obtained when the twins were aged 9, 12, 13, and 14 years. Intrapair variability analysis was performed to identify dietary elements related to BMI changes in subsequent years. BMI-discordant monozygotic twin pairs were also identified to analyze the dietary constituents that may have generated the discordance. After eliminating potential confounding genetic factors, pre-adolescent boys who ate fewer grain products and fruit and consumed more high-fat meat and milk had higher BMIs during adolescence; pre-adolescent girls who consumed more grain products and high-fat meat and milk had higher BMIs during adolescence. Energy intake (EI) at 9 years was not related to BMI in subsequent years. Our study suggests that messages and interventions directed at obesity prevention could take advantage of sex-specific designs and‚ eventually‚ genetic information.

Modeling the data from extended twin pedigrees allows the estimation of increasing complex covariance relationships in which the effects of cultural transmission, nonrandom mating and genotype x environment covariation can be incorporated. However, the power to detect these effects in existing data sets has not yet been examined. The present study examined the effects that different family structures (i.e., the ratio of MZ to DZ families and the importance of cousins vs. avuncular relatives) have on statistical power. In addition, we examined the power to detect genetic and environmental effects within the context of two large data sets (VA30K and the OZVA60K). We found that power to detect additive genetic and cultural transmission effects were maximized by over sampling MZ families. In terms of ascertainment, there was little difference in power between samples that had focused on recruiting a third generation (the children of twins) versus those that had focused on recruiting the siblings of the twins. In addition, we examined the power to detect additive and dominant genetic effects, cultural transmission and assortative mating in the existing VA30K and OZVA60K samples, under two different models of mating: phenotypic assortment and social homogamy. There was nearly 100% power to detect assortative mating and cultural transmission, against a background of small additive and dominant genetic and familial environmental effects. In addition, the power to detect additive or dominant genetic effects quickly asymptoted, so that there was almost 100% power to detect effects explaining 20% or more of the total variance. These results demonstrate that the Cascade model has sufficient power to detect parameters of interest in existing datasets. Mx scripts are available from www.vipbg.vcu.edu/~sarahme/cascade.

Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10−8 and cg01940273, p = 2.34 * 10−8) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10−7; cg09716613, p = 3.23 * 10−7; cg04387347, p = 3.95 * 10−7; and cg02290168, p = 5.23 * 10−7) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

Plasma lipids such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol and triglyceride levels contribute to variation in the risk of cardiovascular disease. The early stages of atherosclerosis in childhood have also been associated with changes in triglycerides, LDL and HDL. Heritability estimates for lipids and lipoproteins for adolescents are in the range .71 to .82, but little is known about changes of genetic and environmental influences over time in adolescence. We have investigated the contribution of genetic and environmental influences to variation in lipids in adolescent twins and their nontwin siblings using longitudinal twin and family data. Plasma HDL and LDL cholesterol, total cholesterol and triglycerides data from 965 twin pairs at 12, 14 and 16 years of age and their siblings have been analyzed. Longitudinal genetic models that included effects of age, sex and their interaction were fitted to assess whether the same or different genes influence each trait at different ages. Results suggested that more than one genetic factor influences HDL, LDL, total cholesterol and triglycerides over time at ages 12, 14 and 16 years. There was no evidence of shared environmental effects except for HDL and little evidence of long-term nonshared environmental effects was found. Our study suggested that there are developmental changes in the genes affecting plasma lipid concentrations across adolescence.

The Study of Personality Architecture and Dynamics (SPeADy) is a German research project that aims to investigate the sources of interindividual differences in intraindividual personality development. The main focus lies in the dynamic interplay between more stable core characteristics and more environmentally malleable surface characteristics, as well as between personality and life experiences over time. SPeADy includes a twin family study encompassing data from 1962 individuals (age: 14–94) of 682 families, including 570 complete twin pairs (plus 1 triplet set), 327 parents, 236 spouses and 145 children of twins. Data collection started in 2016 and data from the first wave are currently obtainable as open source. Available data comprise a broad range of personality variables, such as personality trait constructs, motives, interests, values, moral foundations, religiosity and self-related concepts. For the currently ongoing second wave of data collection, we added retrospective reports on major life events. Special features of this genetically informative study are the extended twin family data and its longitudinal design. Three assessment waves in 2 years’ intervals are planned until 2022. In this article, we briefly describe the design and contents of the SPeADy twin family study as well as some recent findings, future plans and open science issues.

Previous studies have found that major depression and neuroticism are positively associated with urinary incontinence (UI). However, the genetic contribution to these associations has never been investigated. In 2005, a total of 14,094 female twins born 1959–1985 in the Swedish Twin Registry participated in a comprehensive survey on common exposures and complex diseases. Structured questions provided information on UI, depressive symptoms, major depression, and neuroticism. A logistic regression model based on generalized estimating equations (GEE) was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Environmental and genetic influences were assessed in co-twin control analyses and quantitative genetic analyses, which were also used to determine the proportion of the phenotypic correlation explained by familial factors. Major depression, depressive symptoms, and neuroticism were positively associated with all UI subtypes (overall, stress, urge, and mixed UI). In a trivariate Cholesky model with neuroticism, depressive symptoms (or depression), and UI a modest genetic correlation was found between indicators of depression and overall, or stress, UI. The majority of this correlation was independent from neuroticism. In contrast, the genetic factors shared between indicators of depression and urge or mixed UI were entirely in common with neuroticism. In conclusion, depression and neuroticism are associated with UI among premenopausal women: the associations are in part determined by genetic factors in common to the disorders.

During the history of research on multiple maternities, Hellin's law has played a central role as a rule of thumb. It is mathematically simple and approximately correct, but shows discrepancies that are difficult to explain or to eliminate. It has been mathematically proven that Hellin's law does not hold as a general rule. Varying improvements to this law have been proposed. In this paper, we consider how Hellin's law can be used and tested in statistical analyses of the rates of multiple maternities. Such studies can never confirm the law, but only identify errors too large to be characterized as random. It is of particular interest to determine why the rates of higher multiple maternities are sometimes too high or too low when Hellin's law is used as a benchmark. Excesses of triplet and quadruplet maternities are particularly unexpected and challenging. Our analyses of triplet and quadruplet rates indicated that triplet rates are closer to Hellin's law than quadruplet rates. According to our analyses of the twinning rate and the transformed triplet rate and quadruplet rate for Sweden (1751–2000), both triplet and quadruplet rates showed excesses after the 1960s. This is mainly caused by artificial fertility-enhancing reproduction technologies. Regression analyses of twinning and triplet rates yield rather good fits, but deficiencies in the triplet rates are commonly present. We introduced measures of concordance between triplet rates with Hellin's law. According to these measures, historic data showed deficiencies in triplet rates, but recent data revealed excesses, especially found among older mothers. The excesses obtained are in good agreement with other studies of recent data.