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Much of the focus of personality disorder genetics has been aimed at identifying putative genes. Most of the research has been accomplished using a classical monozygotic and dizygotic twin design or adoption study methodologies. This vast body of research has repeatedly shown that the observed variability in personality disorder measures are directly attributable to the action of genes, but few, if any genetic loci have been reliably identified. The chapter explores the reasons for this failure such as the impact of a grand unitary theory of personality function that has created concepts and measures that are poorly suited for genetic studies. Moreover, there are inherent problems in genetic methodology, despite the faith in the latest gene hunting methods that have not been able to overcome psychometric and conceptual issues with personality constructs and measures. Indeed, attempts to revise measures and diagnostic entities have likely exacerbated the problems. Suggestions to overcome these issues, from shifting focus from descriptive personality constructs to active personality constructs such as behavioral choice, the development of personality endophenotypes, and new methods to incorporate data from unrelated individuals in gene hunting studies to increase power and detect small effects of multiple genes are discussed.
To investigate the association of folic acid (FA) supplementation with birth weight, the risk of small for gestational age (SGA) and low birth weight (LBW) in singleton and twin pregnancy.
A population-based cross-sectional survey.
Twenty counties and ten districts in Shaanxi Province of northwestern China, 2013.
28 174 pregnant women with their infants, covering 27 818 single live births and 356 twin live births.
The prevalence of FA supplementation in singletons and twins was 63·9 and 66·3 %. The mean birth weight was 3267 (sd 459·1) g, 2525 (sd 534·0) g and 2494 (sd 539·5) g; the prevalence of SGA was 14·3, 51·4 and 53·4 %; the prevalence of LBW was 3·4, 42·4 and 46·6 % among singleton, twin A and twin B, respectively. Compared with non-users, women with FA supplementation were (β 17·3, 95 % CI 6·1, 28·4; β 166·3, 95 % CI 69·1, 263·5) associated with increased birth weight, lower risk of SGA (OR 0·85, 95 % CI 0·80, 0·92; OR 0·45, 95 % CI 0·30, 0·68) and LBW (OR 0·82, 95 % CI 0·71, 0·95; OR 0·50, 95 % CI 0·33, 0·75) in singletons and twins, and more prominent effects in twins. Moreover, there were significant interactions between FA supplementation and plurality on birth weight, SGA and LBW.
The present study suggests the association of periconceptional 0·4 mg/d FA supplementation with increased birth weight and reduced risk of SGA and LBW in both singletons and twins, and this association may be more prominent in twins.
Quantitative genetic research includes a range of genetically sensitive research designs that rely on family samples to study the relative importance of genes and environments for individual difference in psychopathology. The past decades have seen an increase in quantitative genetic research focused on the origins of childhood and adolescent psychopathology. Evidence from this research univocally demonstrates that genetic factors play an important role in all forms of psychopathology, and that these genetic factors interact with the environment to shape the development of childhood and adolescent psychopathology. The goal of this chapter is to highlight how recent methodological developments and the accumulation of longitudinal data now allow quantitative genetic research to go beyond asking “if” genetic factors are important, to instead address important questions regarding gene-environment interplay in the development of childhood and adolescent psychopathology. It begins by introducing the family, adoption, and twin designs, and summarizing the main findings from these methods for child and adolescent psychopathology. It then provides concrete examples of how multivariate and longitudinal quantitative genetic research designs can be used to address important questions regarding etiology across different levels of symptom severity, comorbidity, and development, and to study gene-environment interplay in child and adolescent psychopathology. It concludes by highlighting important outstanding questions in childhood psychopathology that need to be addressed in future quantitative genetic research.
Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders.
In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25).
Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions.
Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.
Using vital statistics in Japan (1995–2008), 154,578 live-born twin pairs (128,236 monozygotic [MZ] and 180,920 dizygotic [DZ]) were identified. The proportion of severe discordance among live-born twin births was twice as high in Japanese than Caucasian infants. There were 1858 MZ and 1620 DZ infant deaths. Computation of the relationship between infant mortality rate and birth weight discordance among the twins was performed. Discordance levels were classified into seven groups: <5%, five groups from 5–9% to 25–29%, and ≥30%.The mortality rate was significantly higher in MZ than DZ twins for discordances except at 5–9% and 10–14%. The lowest rate for MZ twins was at 5–9% (7.5 per 1000 live twins) and significantly increased from 10–14% (9.4) to ≥30% (83.4), while the lowest rate for DZ twins was at <5% (6.7), which significantly increased at 10–14% (8.0) and from 25–29% (12.1) to ≥30% (35.5). The relationship was also computed in two gestational age groups (<28 and ≥28 weeks). For births at <28 weeks, three discordances (after 20–24%) in MZ twins were associated with adverse mortality rate. For births at ≥28 weeks, the same relationship was obtained after 10–14% in MZ and after 20–24% in DZ twins. The relationship from 2002 to 2008 showed that the mortality rates significantly increased after 10–14% for both types of twins. In conclusion, five discordance levels in MZ and three levels in DZ twins were associated with adverse mortality rates.
Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18–67 years and free from diabetes at baseline during 1997–2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.
Scholarly literature claims that health declines in populations when optimism about investing in the future wanes. This claim leads us to describe collective optimism as a predictor of selection in utero. Based on the literature, we argue that the incidence of suicide gauges collective optimism in a population and therefore willingness to invest in the future. Using monthly data from Sweden for the years 1973–2016, we test the hypothesis that the incidence of suicide among women of child-bearing age correlates inversely with male twin births, an indicator of biological investment in high-risk gestations. We find that, as predicted by our theory, the incidence of suicide at month t varies inversely with the ratio of twin to singleton male births at month t + 3. Our results illustrate the likely sensitivity of selection in utero to change in the social environment and so the potential for viewing collective optimism as a component of public health infrastructure.
In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.
The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men, particularly early identification of risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). It comprises a subset of over 1600 twins from the Vietnam Era Twin Registry. Twins live all over the USA. Assessments began when participants were in their 50s. Follow-ups were conducted every 5–6 years, and wave 3 has been completed as of this writing. The age range of participants is narrow (about 10 years). An extensive neurocognitive test battery has added precision in assessing differences in middle-aged adults, and predicting progression to MCI. Young adult cognitive test data (at an average age of 20 years) provide a means of disentangling aging effects from longstanding differences. Genome wide genotyping and plasma assays of AD biomarkers from waves 1 and 3 were conducted in wave 3. These features make the VETSA ideal for studying the heterogeneity of within-individual trajectories from midlife to old age, and for early detection of risk factors for cognitive decline.
The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989–2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.
Despite the well-known relevance of twin studies in the medical and social sciences and the growing number of twin registries throughout the world, Latin America has not fully incorporated into the twin research community. We describe the first steps taken toward developing a twin registry in Mexico: its aim, organization, recruiting potential and main short-term objectives.
Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program — Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.
Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1–12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.
The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight development, obesity, life satisfaction and personality. To date, five waves of data collection have been completed and the sixth is now planned. Data from the FT16 cohort have contributed to several hundred studies and many substudies, with more detailed phenotyping and collection of omics data completed or underway. FT16 has also contributed to many national and international collaborations.
Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA’s recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA’s knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains.
Meta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.
The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941–949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351–357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.
The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.
The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources — the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping — allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.
The new West Japan Twins and Higher Order Multiple Births Registry was established by recruiting young twins and multiple births and by referrals from public health centers in the 1990s. The participants included in the survey comprised over 7800 twins and 4241 higher order multiples, and their families. Specifically, the present registry contains one of the largest triplet samples in the world. For these twins and multiples, data on year of delivery, mode of delivery, gestational age, intrapartum complications, longitudinal physical measures, motor milestones, cerebral palsy and feeding methods were obtained from records in the Maternal and Child Health Handbooks and schools. Participating mothers were asked to indicate family structure, parental educational history, maternal sleeping time, maternal health condition, maternal and paternal age at multiple delivery, complications during pregnancy, handedness of multiples and age at menarche of multiples. However, the zygosity differed among the various collaborating public health centers according to factors such as the time of investigation. Follow-up questionnaires have been mailed out every 3–4 years for longitudinal studies. This article describes the goals of this registry, recruitment of multiples and the focus of the study. The goals of this registry are not only to conduct research on human genetics and maternal and child health, but also to contribute to providing appropriate information for families with multiples.