Discordant monozygotic (MZ) twin methodologies are considered one of the foremost statistical approaches for estimating the influence of environmental factors on phenotypic variance. Limitations associated with the discordant MZ twin approach generates an inability to estimate particular relationships and adjust estimates for the confounding influence of gene-nonshared environment interactions. Recent advancements in molecular genetics, however, can provide the opportunity to address these limitations. The current study reviews an alternative technique, genetically adjusted propensity scores (GAPS) matching, that integrates observed genetic and environmental information to adjust for the confounding of these factors in nonkin individuals. Simulations and a real data example were used to compare the GAPS matching approach to the discordant MZ twin method. Although the results of the simulated comparisons demonstrated that the discordant MZ twin approach remains the more robust statistical technique to adjust for shared environmental and genetic factors, GAPS matching — under certain conditions — could represent a viable alternative when MZ twin samples are unavailable. Overall, the findings suggest that GAPS matching can potentially provide an alternative to the discordant MZ twin approach when limited variation exists between identical twin pairs. Moreover, the ability to adjust for gene-nonshared environment interactions represents a potential advancement associated with the GAPS approach. The limitations of the approach, as well as polygenic risk scores, are also discussed.

Erikson asked what makes some people care for the future of the species and others not, calling this ‘generativity vs. stagnation’. In three studies, we addressed structure of this trait and its heritability. Study 1 (N = 1570), using structural models of the Loyola Generativity Scale , revealed three correlated factors consisting of (1) Establishing and aiding the next generation; (2) Maintaining the world; and (3) Symbolic immortality through a positive legacy. Study 2 (N = 311) successfully replicated this structure in an independent UK sample. Study 3 tested genetic and environmental influences on generativity. All three factors showed significant and substantial heritable influence. A general factor was required, which was also heritable. In resolving previous uncertainty over the transmission of generativity across generations, shared environmental transmission models fit poorly. Substantial unique environmental effects suggest strong cultural impacts on concern for the species. Generativity researchers may usefully adopt this three-factor scoring system, allowing research on the predictive power of each component of generativity as well as molecular genetic or biological studies.

Dermatoglyphs are epidermal ridge configurations on the fingers, palms and soles that are formed during fetal development, and therefore only the intrauterine environment can have any influence on their formation. This study aims at investigating the genetic and environmental contribution in determining quantitative dermatoglyphic traits in 32 monozygotic (MZ) and 35 dizygotic (DZ) same-sex twins from the Albanian population of Kosovo. All genetic analyses were run in the statistical program Mx. After assumptions testing, based on the pattern of MZ–DZ correlations, univariate models were fitted to the data in order to estimate additive genetic (A), common (C) and individual (E) environmental influences for all variables. The exception was the atd-angle for which a model with nonadditive genetic (D) influences was tested, since DZ correlations were less than half of MZ correlations. Goodness of fit of the full ACE or ADE model was compared to the saturated model. The fit of nested models (AE, CE, DE or E) was compared to the full models (ACE or ADE). Our results indicate that additive genetic component strongly contributes to individual differences in finger ridge counts (49−81%), and weakly (0−50%) on the formation of the palmar ridge counts between the palmar triradii a, b, c, and d. The specific pattern found for the atd-angle implies the impact of a nonadditive genetic component, possibly the effect of a major gene. Further, more powered studies are needed to confirm this pattern, especially for resolving the issue of the huge difference in MZ and DZ twin similarity for the atd-angle palmar trait.

Human genetic and genomic information (HGI) is being generated, utilized and accessed across a wide range of healthcare settings. While traditionally clinical genetics services have maintained guardianship and enforced rigid protections of human genetic information, this is no longer practical or feasible as genetic knowledge continues to evolve, expand and inform various aspects of healthcare. Today, many healthcare professionals of varied backgrounds and areas of expertise are looking to genetic and genomic information to screen and/or diagnose genetic conditions and to guide medical management and treatment options. This position statement provides guidance for all healthcare professionals who may be handling human genetic and/or genomic information as part of their practice and outlines considerations relevant to protection, storage, access and sharing of HGI in Australasia. Illustrative cases are used to highlight various sensitivities of genetic and genomic information and challenges these may pose in modern healthcare settings. In essence, this position statement seeks to highlight and advocate for both individual interests as well as the interests of the broader family network.

Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or ‘twin-only trials’. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18−95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained — in roughly equal parts — by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.

Using data from the Midlife Development in the USA (MIDUS) sample (3070 men and 3182 women) and the Wisconsin Longitudinal Study (WLS; 2240 men and 2346 women), we aimed to investigate whether religious, ethnic and racial in-group preferences as well as religious homogamy are associated with reproductive outcome in terms of number of children. Using data from the MIDUS twin sample, we further estimated the inherited genetic component of in-group attitudes. Additionally, we analyzed the association of ∼50 polygenic scores (PGSs) recently published for the WLS study and in-group attitudes as an indicator of potential pleiotropic effects. We found in both samples that, with one exception, religious though not other in-group attitudes are associated with a higher reproductive outcome. Also, religious homogamy is associated with higher average number of children. The inherited component of all in-group attitudes ranges from ∼21% to 45% (MIDUS twin sample). PGSs associated with religious behavior are significantly positively associated with religious in-group attitudes as well as family attitudes. Further associations are found with PGS on life satisfaction (work) and, negatively, with PGS for any sort of addiction (smoking, alcohol and cannabis use), indicating pleiotropy. We conclude that the positive association between religious in-group attitudes as well as religious homogamy and reproductive outcome may indicate selective forces on religious in-group behavior. As all investigated in-group attitudes, however, have a substantial inherited component, we further speculate that potential previous reproductive benefits of racial and ethnic in-group preferences, if they ever existed, might have been substituted by religious in-group preferences.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

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.

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

Over the previous decades, twinning rates worldwide have increased remarkably. This study aimed to describe changes in multiple birth rates and related demographic characteristics, such as maternal age and the level of education of parents in South Korea from 1981 to 2019. This study analyzed birth data obtained from the Korean Statistical Information Service. From 1981 to 2019, the total twinning rate increased from 5 to 22.5 pairs per 1000 births. This rapid increase was due to an increase in dizygotic twin births, which mainly occurred in mothers aged between 30 and 39 years. The average maternal age of multiples increased from 26.06 years in 1981 to 33.98 years in 2019, suggesting that a delay in childbearing contributed to the increase in the twinning rate. The percentage of mothers of multiples who completed a college or higher degree (CHD) increased by 1000% from 1981 to 2019, indicating that a sharp increase in the level of education of females in part explains the delay in childbearing. The percentages of individuals who completed a CHD were higher among parents of multiples than among those of singletons in recent years when public funding arrangements for fertility treatments were available. This result suggested that completion of higher education may be associated with increased use of assisted reproductive technology (ART) independent of the financial status of couples. Taken together, the analysis suggested that increased maternal age, ART and the increased number of females who completed CHD may be responsible for the remarkable increase in the rates of multiple births in South Korea in the last four decades.

Accurate zygosity determination is a fundamental step in twin research. Although DNA-based testing is the gold standard for determining zygosity, collecting biological samples is not feasible in all research settings or all families. Previous work has demonstrated the feasibility of zygosity estimation based on questionnaire (physical similarity) data in older twins, but the extent to which this is also a reliable approach in infancy is less well established. Here, we report the accuracy of different questionnaire-based zygosity determination approaches (traditional and machine learning) in 5.5 month-old twins. The participant cohort comprised 284 infant twin pairs (128 dizygotic and 156 monozygotic) who participated in the Babytwins Study Sweden (BATSS). Manual scoring based on an established technique validated in older twins accurately predicted 90.49% of the zygosities with a sensitivity of 91.65% and specificity of 89.06%. The machine learning approach improved the prediction accuracy to 93.10%, with a sensitivity of 91.30% and specificity of 94.29%. Additionally, we quantified the systematic impact of zygosity misclassification on estimates of genetic and environmental influences using simulation-based sensitivity analysis on a separate data set to show the implication of our machine learning accuracy gain. In conclusion, our study demonstrates the feasibility of determining zygosity in very young infant twins using a questionnaire with four items and builds a scalable machine learning model with better metrics, thus a viable alternative to DNA tests in large-scale infant twin studies.

There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.

The present study aimed to determine the genetic and environmental etiology of the association between childhood negative emotionality (NE) and hyperactivity/inattention problems (HIP) using South Korean elementary school twins (mean age = 10.19 years, SD = 1.79 years). Telephone interviews were given to mothers of 919 twins (229 monozygotic males: 112 pairs and 5 individuals; 148 dizygotic males: 73 pairs and 2 individuals; 180 monozygotic females: 87 pairs and 6 individuals; 103 dizygotic females: 50 pairs and 3 individuals; 259 opposite-sex dizygotic twins: 127 pairs and 5 individuals) to assess their children’s NE and HIP. Consistent with prior studies, the phenotypic correlation between NE and the HIP was moderate (r = .29; 95% CI = .24, .34). Model-fitting analysis revealed that additive genetic and nonshared environmental influences on NE were .45 (95% CI [.34, .54]) and .55 (95% CI [.46, .66]), respectively, and that additive and nonadditive genetic, and nonshared environmental influences on HIP were .08 (95% CI [.03, .26]), .41 (95% CI [.21, .51]) and .51 (95% CI = .42, .61), respectively. In addition, the additive genetic correlation between NE and HIP was 1.0 (95% CI [.52, 1.00]), indicating that additive genetic factors are entirely shared between the two phenotypes. Nonadditive genetic influences were unique to HIP and not responsible for the NE-HIP association. Nonshared environmental correlation was significant but modest (re = .18, 95% CI [.06, .30]).

Twin studies of physical exercise for Asian twins are sparse. This study aimed to examine genetic and environmental influences on frequency of vigorous exercise (FVE) in South Korean twins, with a special emphasis on sex effects. Telephone interviews on FVE were administered to 1757 twins (mean age = 19.05 years, SD = 3.01 years). Tetrachoric correlations were significantly different between monozygotic (MZ) and dizygotic (DZ) twins in males (.40 vs. .12), but they were similar in females (.44 vs. .45), suggesting the importance of genetic factors in FVE in males and that of common environmental factors in females. A scalar sex-limitation model incorporating age as a modifier was applied to data. The results revealed that genetic, common and individual environmental influences did not vary significantly with age, but differed across two sexes, confirming twin correlational analyses. In the best-fitting model, additive genetic and individual environmental influences on FVE were, respectively, .35 (95% CI [.26, .39]) and .65 (95% CI [.61, .74]) in males, and common and individual environmental influences were, respectively, .45 (95% CI [.35, .53]) and .55 (95% CI [.47, .65]) in females. These results contrasted starkly with recent findings from a large sample of Chinese adult twins (age >18 years), in which most variance (≥95%) of vigorous physical activity was attributable to common environmental influences in both sexes. Replications in other Asian samples are clearly needed.

Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17−93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04–1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.

Research has emphasized the genetic basis of individual differences in body mass index (BMI); however, genetic factors cannot explain the rapid rise of obesity. Eating behaviors have been stipulated to be the behavioral expression of genetic risk in an obesogenic environment. In this study, we decompose variation and covariation between three key eating behaviors and BMI in a sample of 698 participants, consisting of 167 monozygotic, 150 dizygotic complete same-sex female twins and 64 incomplete pairs from a population-based twin registry in the southeast of Spain, The Murcia Twin Registry. Phenotypes were emotional eating, uncontrolled eating and cognitive restraint, measured by the Three Factor Eating Questionnaire and objectively measured BMI. Variation in eating behaviors was driven by nonshared environmental factors (range: 56%−65%), whereas shared environmental and genetic factors were secondary. All three eating behaviors were correlated with BMI (r = .19–.25). Nonshared environmental factors explained the covariations (Emotional eating–Uncontrolled eating: rE = .54, 95% CI [.43, .64]; BMI–Cognitive restraint: rE = .15, 95% CI [.01, .28]). In contrast to BMI, individual differences in eating behaviors are mostly explained by nonshared environmental factors, which also accounted for the phenotypic correlation between eating behaviors and BMI. Due to the sample size, analyses were underpowered to detect contributions of additive genetic or shared environmental factors to variation and covariation of the phenotypes. Although more research is granted, these results support that eating behaviors could be viable intervention targets to help individuals maintain a healthy weight.

We compare the power of two different approaches to detect passive genotype–environment (GE) covariance originating from cultural and genetic transmission operating simultaneously. In the traditional nuclear twin family (NTF) design, cultural transmission is estimated from the phenotypic covariance matrices of the mono- and dizygotic twins and their parents. Here, phenotyping is required in all family members. A more recent method is the transmitted–nontransmitted (T–NT) allele design, which exploits measured genetic variants in parents and offspring to test for effects of nontransmitted alleles from parents. This design requires two-generation genome-wide data and a powerful genome-wide association study (GWAS) for the phenotype in addition to phenotyping in offspring. We compared the power of both designs. Using exact data simulation, we demonstrate three points: how the power of the T–NT design depends on the predictive power of polygenic risk scores (PRSs); that when the NTF design can be applied, its power to detect cultural transmission and GE covariance is high relative to T–NT; and that, given effect sizes from contemporary GWAS, adding PRSs to the NTF design does not yield an appreciable increase in the power to detect cultural transmission. However, it may be difficult to collect phenotypes of parents and the possible importance of gene × age interaction, and secular generational effects can cause complications for many important phenotypes. The T–NT design avoids these complications.