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.

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983–1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene–environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

To improve global human capital, an understanding of the interplay of endowment across the full range of socioeconomic status (SES) is needed. Relevant data, however, are absent in the nations with the most abject poverty (Tucker-Drob & Bates, 2016), where the lowest heritability and strong effects of SES are predicted. Here we report the first study of biopsychosocial gene–environment interaction in extreme poverty. In a sub-Saharan sample of early teenage twins (N = 3192), we observed substantial (~30–40%) genetic influence on cognitive abilities. Surprisingly, shared environmental influences were similar to those found in adolescents growing in Western affluent countries (25–28%). G × SES moderation was estimated at aˋ = .06 (p = .355). Family chaos did not moderate genetic effects but did moderate shared environment influence. Heritability of cognitive abilities in extreme poverty appears comparable to Western data. Reduced family chaos may be a modifiable factor promoting cognitive development.

The National Project on Achievement in Twins (NatPAT) began in 2017 as part of the third funding cycle of the Florida Learning Disabilities Research Center, a program project grant funded by the Eunice Kennedy Shriver National Institute of Child Health and Development. NatPAT will have a nationally representative sample of elementary school-aged twins in the United States. The overall goal of the project is to uncover salient factors, including genetic and environmental influences, which contribute to the co-development of reading and math performance during the critical developmental period of elementary school. Here we present the specific aims, methods and materials, and future directions of the project.

The Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years’ research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King’s College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several ‘omic’ technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the ‘TwinsUK’ resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.

Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.

The Norwegian Twin Registry (NTR) is maintained as a research resource that was compiled by merging several panels of twin data that were established for research into physical and mental health, wellbeing and development. NTR is a consent-based registry. Where possible, data that were collected in previous studies are curated for secondary research use. A particularly valuable potential benefit associated with the Norwegian twin data lies in the opportunities to expand and enhance the data through record linkage to nationwide registries that cover a wide array of health data and other information, including socioeconomic factors. This article provides a brief description of the current NTR sample and data collections, information about data access procedures and an overview of the national registries that can be linked to the NTR for research projects.

The German Twin Family Panel (TwinLife) is a German longitudinal study of monozygotic and dizygotic same-sex twin pairs and their families that was designed to investigate the development of social inequalities over the life course. The study covers an observation period from approximately 2014 to 2023. The target population of the sample are reared-together twins of four different age cohorts that were born in 2009/2010 (cohort 1), in 2003/2004 (cohort 2), in 1997/1998 (cohort 3) and between 1990 and 1993 (cohort 4). In the first wave, the study included data on 4097 twin families. Families were recruited in all parts of Germany so that the sample comprises the whole range of the educational, occupational and income structure. As of 2019, two face-to-face, at-home interviews and two telephone interviews have been conducted. Data from the first home and telephone interviews are already available free of charge as a scientific use-file from the GESIS data archive. This report aims to provide an overview of the study sample and design as well as constructs that are unique in TwinLife in comparison with previous twin studies — such as an assessment of cognitive abilities or information based on the children’s medical records and report cards. In addition, major findings based on the data already released are displayed, and future directions of the study are presented and discussed.

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.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.

The University of São Paulo Twin Panel (Painel USP de Gêmeos), based at the Institute of Psychology of the University of São Paulo, started formally in 2017. Our registry is new, but in only two years of formal existence, it comprises a volunteer sample of 4826 registered individuals (98% twins and 2% higher-order multiples), recruited at the University of São Paulo and by social media campaigns. Our main aim is to conduct and promote research with twins on psychological processes and behavior. The University of São Paulo is the largest higher education and research institution in South America, and the Painel USP de Gêmeos has great potential for fostering research on twin-related issues from a psychological perspective in Brazil and South America.

Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5783 English Longitudinal Study of Ageing (ELSA) participants (mean age = 65.49, SD = 9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004–2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE = 7.2%). Greater odds of having adequate health literacy were associated with a 1 standard deviation higher polygenic score for general cognitive ability [OR = 1.34, 95% CI (1.26, 1.42)], verbal-numerical reasoning [OR = 1.30, 95% CI (1.23, 1.39)], and years of schooling [OR = 1.29, 95% CI (1.21, 1.36)]. Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health [OR = 0.92, 95% CI (0.87, 0.98)] and schizophrenia [OR = 0.91, 95% CI (0.85, 0.96)). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic etiology. Larger studies are required to obtain accurate estimates of SNP-based heritability and to discover specific health literacy-associated genetic variants.

We sought to investigate the risk of incident major depressive disorder (MDD) attributable to a range of sleep disorders in the Danish population. Data were obtained by linking longitudinal Danish population-based registers. A total of 65,739 individuals who had first onset of depression between 1995 and 2013 were selected as cases. For each case, a set of 20 controls of the same sex, birth month and year and who had not had depression by the date that the case was diagnosed were selected at random form the population (N = 1,307,580 in total). We examined whether there was an increased rate of prior sleep disorders in MDD cases compared to controls using conditional logistic regression. An increased risk of incident depression in cases was found for all sleep disorders analyzed. Highest incidence rate ratios (IRRs) were found for circadian rhythm disorders (IRR = 7.06 [2.78–17.91]) and insomnia of inorganic origin (IRR = 6.76 [4.37–10.46]). The lowest estimated IRR was for narcolepsy (IRR = 2.00 [1.26–3.17]). Those diagnosed with a sleep disorder in the last 6 months were at highest risk of developing depression compared to those with at least 1 year since diagnosis (3.10 vs. 2.36). Our results suggest that having any sleep disorder is a risk factor for incident depression. Depression screening should be considered for patients with sleep disorders, and where possible, long-term follow-up for mental health problems is advisable.

A literature review was carried out to identify pre and perinatal characteristics associated with variation in Apgar scores in population-based studies. The parameters identified in the literature search were included in the classical twin design study to estimate effects of pre and perinatal factors shared and nonshared by twins and to test for a contribution of genetic factors in 1- and 5-min Apgar scores in a large sample of Dutch monozygotic (MZ) and dizygotic (DZ) twins. The sample included MZ and DZ twins (N = 5181 pairs) recruited by the Netherlands Twin Register shortly after birth, with data on prenatal characteristics and Apgar scores at first and/or fifth minutes. The ordinal regression and structural equation modeling were used to analyze the effects of characteristics identified in the literature review and to estimate genetic and nongenetic variance components. The literature review identified 63 papers. Consistent with the review, we observed statistically significant effects of birth order, zygosity and gestational age (GA) for 1- and 5-min Apgar scores of both twins. Apgar scores are higher in first-born versus second-born twins and DZ first-born versus MZ first-born twins. Birth weight had an effect on the 5-min Apgar of the first born. Fetal presentation and mode of delivery had different effects on Apgar scores of first- and second-born twins. Parental characteristics and chorionicity did not have significant main effects on Apgar scores. The MZ twins’ Apgar correlations equaled the DZ Apgar correlations. Our analyses suggest that individual differences in 1- and 5-min Apgar scores are attributable to shared and nonshared pre and perinatal factors, but not to genotypic factors of the newborns. The main predictors of Apgar scores are birth order, zygosity, GA, birth weight, mode of delivery and fetal presentation.

Genetic and environmental influences on age at menarche (AAM) have rarely been examined in Asian females. This study aimed to investigate the heritability of AAM in South Korean female twins. The AAM data from 1370 female twins (933 monozygotic [MZ] twins, 294 dizygotic [DZ] twins and 160 female members of opposite-sex DZ twins) born between 1988 and 2001 were analyzed. The age of the sample at the time of the assessment ranged from 16 to 28 years with a mean of 19.3 (SD = 2.2) years. The mean AAM in the total sample was 12.49 (SD = 1.41) years. Although the mean AAM decreased with increasing birth years, it levelled off in birth years 2000–2001. Maximum likelihood MZ and DZ twin correlations were 0.72 [95% CI (0.67, 0.76)] and 0.35 [95% CI (0.19, 0.50)], respectively. The results of model-fitting analysis indicated that the additive genetic and individual-specific environmental effects were 72% [95% CI (67%, 76%)] and 28% [95% CI (24%, 33%)], respectively. Neither nonadditive genetic nor shared environmental effects were significant.

Somatization is known to be more prevalent in Asian than in Western populations. Using a South Korean adolescent and young adult twin sample (N = 1754; 367 monozygotic male, 173 dizygotic male, 681 monozygotic female, 274 dizygotic female and 259 opposite-sex dizygotic twins), the present study aimed to estimate heritability of somatization and to determine common genetic and environmental influences on somatization and hwabyung (HB: anger syndrome). Twins completed self-report questionnaires of the HB symptoms scale and the somatization scale via a telephone interview. The results of the general sex-limitation model showed that 43% (95% CI [36, 50]) of the total variance of somatization was attributable to additive genetic factors, with the remaining variance, 57% (95% CI [50, 64]), being due to individual-specific environmental influences, including measurement error. These estimates were not significantly different between the two sexes. The phenotypic correlation between HB and somatization was .53 (p < .001). The bivariate model-fitting analyses revealed that the genetic correlation between the two symptoms was .68 (95% CI [.59, .77]), while the individual-specific environmental correlation, including correlated measurement error, was .41 (95% CI [.34, .48]). Of the additive genetic factors of 43% that influence somatization, approximately half (20%) were associated with those related to HB, with the remainder being due to genes unique to somatization. A substantial part (48%) of individual environmental variance in somatization was unrelated to HB; only 9% of the environmental variance was shared with HB. Our findings suggest that HB and somatization have shared genetic etiology, but environmental factors that precipitate the development of HB and somatization may be largely independent from each other.