Welcome to the special issue of Twin Research and Human Genetics on ‘Twin Registries Worldwide: An Important Resource for Scientific Research’. The twin method can be traced back to Galton's (Reference Galton1876) assertion that twins can help tease out effects of genes and environment. It is now well recognized in the scientific community that twins are powerful and flexible tools to achieve understanding of the biological substrate of complex human diseases and behaviors. The twin method was traditionally used to estimate heritability, and has now evolved to locate genetic variants that explain heritability, and to study the regulation of gene expression, including epigenetic modifications on the genetic material, cellular processes involving metabolites, the human microbiome, and pharmacogenomics for human variations in response to medications. At the same time, as indicated in this special issue, many twin researchers have also begun to search specific environmental sources of phenotypic variation that interact with genetic factors. Twin pairs discordant for diseases and behaviors and the quantitative genetic method with structural equation modeling techniques are especially useful to detect these environmental sources. The paradigm of twin studies is now being shifted toward understanding of how macro- and micro-environmental factors interplay with complex biological processes.
In 2002, when Twin Research published its first special twins cohort issue (Busjahn, Reference Busjahn2002), 36 papers were included. As it became apparent that twin research was continuing to expand, another special issue was published in 2006 (Busjahn & Hur, Reference Busjahn and Hur2006), which included 53 papers. In the current issue we are able to collect 71 papers in total. Therefore, this would indicate that the number of twin research cohorts has almost doubled during the past 10 years (Figure 1). The number of countries involved in twin research has also increased; the 2002 issue presented data from 16 countries, which increased to 20 in 2006, and in this issue it has increased to 28 countries (Figure 2). These figures assure us that twin research is a fast-growing field of science across the globe. Traditionally, it has been suggested that twin studies limit their conclusions to explanation of variation within a population (Plomin et al., Reference Plomin, DeFries, McClearn and McGuffin2001). However, as many twin registries in this issue are either multinational or are inviting international collaborations, twin analyses are starting to move beyond within-population analyses (Figure 2 and Table 1). This special issue is a comprehensive coverage of currently active twin cohorts around the world. While many of the papers in this issue have updated their previous articles published in the 2002 and/or 2006 special issues, describing the progress they have made, new twin registries that have emerged during recent years have also been included in this issue.
TABLE 1 An Overview of Twin Registries Worldwide
aNames of the corresponding authors are indicated in parenthesis when the first author is different from the corresponding author; for two-author papers, both authors’ names are indicated.
bTwins = individual twins, including cases with missing co-twins. For most twin registers, the recruitment is ongoing and, therefore, the sample size is likely to change.
cAge at assessment or current age.
dQ = questionnaire, DNA = analysis of DNA markers, NA = not applicable.
FIGURE 1 Number of papers in the three special issues on twin registers in the world published in Twin Research (2002) and Twin Research and Human Genetics (2006 and 2013).
FIGURE 2 Location of twin studies featured in this issue. Each study is shown as a double star.
New Twin Registries
The Cuban Twin Registry is a nationwide, population-based registry consisting of approximately 58,000 pairs of twins who were identified through the National Citizen Identity Registry. This twin registry is almost free of ascertainment bias as it includes over 99.9% of all twins available from the total population in Cuba. Undoubtedly, this registry is a powerful resource to study genetic and environmental etiologies of complex diseases in the Cuban population. The successful construction of the registry appears largely due to the efforts of door-to-door visits and in-person interviews that the investigators made, as well as the support of the Cuban government.
A nationwide, representative school-aged twin registry is currently being developed in the Russian Federation and the Kyrgyz Republic. Utilizing 50,000 school rosters across the country, the investigators are forming a registry of over 100,000 twins aged 7 to 18 years with a general aim to resolve the issues of gene–environment interactions for the development of school achievement and related traits. The investigators also seek international collaborations to use this huge resource to study cross-cultural comparisons on education-related traits.
New registries in two African countries, Guinea-Bissau and Nigeria, are also notable. Although both registries aim to study children and adolescent twins, the ascertainment schemes of the two registries are different. Whereas the Guinea-Bissau Twin Registry collects twin data mainly from hospitals, focusing on diseases and related traits, the Nigerian Twin and Sibling Registry recruits twins largely from schools, and its primarily interests are psychological and mental health variables. As Africans are known to have the highest twin birth rate in the world (Bulmer, Reference Bulmer1970), these two registers are likely to increase their sample size rapidly, which will provide new opportunities to study complex human behaviors and disease traits of Africans living in extremely deprived environments.
This issue also presents a brief history and initial findings of the Hungarian, Portugese, and Turkish twin registries in Europe. Although these three registries started with small regional samples and meager financial resources, they are being extended to the whole country. In Asia, nationwide twin registries are being established in Malaysia, Mongolia, and Thailand. The progress and research interests of these three registries are also briefly described in this issue.
We have also included many new twin registries from the United States. For example, the Arizona Twin Registry, which was developed from 600 young twins ascertained from birth records in the state of Arizona, offers a new resource to explore interesting questions of how early competency and resilience develop and moderate genetic and environmental risk factors for childhood physical and mental health problems. The Boston University Twin Project (BUTP) is also a new longitudinal study of young twins recruited from birth records of the state of Massachusetts. The target phenotypes of the BUTP are childhood temperament and behavior problems, with specific focus on activity level. The unique feature of the BUTP is the use of multiple mechanical measures to assess phenotypes across multiple contexts. These measurement strategies are important because they can help increase generality of the findings, as well as improve our understanding of context-specific effects in the development of childhood temperament and behavior problems.
The Carolina African American Twin Study of Aging (CAATSA) was founded to study genetic and environmental influences on health and related traits in African Americans. CAATSA is, to our knowledge, the only twin registry in the world that focuses on African-American twins. The number of African-American twins who participate in twin registries in the United States (e.g., The Mid-Atlantic Twin Registry) is currently increasing in spite of the challenges with engaging ethnic minorities in scientific research. Together with twins who take part in twin studies in Africa, the CAATSA sample and other African-American twins in several registries in this issue may provide important information to develop optimal prevention and intervention strategies to reduce health disparities between people of African and European origin.
The Texas Twin Project was developed to address the question of whether and how family socioeconomic status (SES) and other environmental contexts can moderate genetic influences on psychosocial outcomes in children and adolescents. Taking advantage of the large population size and a high poverty rate in the state of Texas, the investigators were able to maximize representation of low SES families and racial/ethnic minorities in their sample. When the ascertainment of twin families is complete, the project will undoubtedly become an important resource to explore the effects of interactions between genes and social contexts on child development.
Prescott et al.'s article in this issue presents their plans to reassess 2,500 pairs of twins and approximately 90,000 siblings who participated in Project Talent (Flanagan, Reference Flanagan1962) in the 1960s. In addition to a large, nationally representative sample, the availability of longitudinal data on families, schools, and communities, as well as students themselves, are great strengths of the sample, which will enable investigators to address the roles of environments in educational outcomes in a genetically sensitive design.
The adoption design is another major method to study the effects of genes and environments and their interplays on human behaviors and diseases. As it is important and necessary to compare and integrate the findings of adoption and twin studies to resolve many research questions, we invited two large, longitudinal adoption registries to report in this issue: the Colorado Adoption Project and the Early Growth and Development Study. The two papers presented their brief histories, the procedures and strategies to recruit and retain their samples, and their key findings to date.
An Overview of Twin Registries
The papers in this issue provide an overview of how twin registries can be developed and maintained, as well as various research questions that twin researchers are currently interested in (Table 1). While some papers discuss how twins can be used to address various research questions, others reviewed the main findings on the basis of their twin registries.
Twin registries cover all ages, with some recruiting before or at birth (e.g., Peri/Postnatal Epigenetic Twins Study [PETS], the Australian Twin Registry [ATR], The North of England Survey of Twin and Multiple Pregnancy, The East Flanders Prospective Twin Survey, the Italian Twin Register, and the West Japan Twins and Higher Order Multiple Births Registry) through to those focusing on all twins, as well as those focusing on older twins (e.g., the Osaka University Center for Twin Study, The Vietnam Era Twin Registry, the Carolina African American Twin Study of Aging, and the Consortium on Interplay of Genes and Environment across Multiple Studies [IGMES]), which extend to 102-year-old twins.
Sample sizes of twin registries in the current issue varied greatly, from a few hundred to close to 200,000 twins (the Swedish Twin Registry, the Danish Twin Registry). This issue shows that over 1.5 million subjects are now participating in twin studies around the world! Of note are several large nationwide twin registers in Northern Europe, which increase their sample sizes, representativeness, and research areas by linking their twin cohorts with national demographic, social, and health registers (the Danish Twin Registry, the Finnish Twin Cohort Study, the Norwegian Twin Registry, and the Swedish Twin Registry).
Many twin registries are currently carrying out longitudinal assessments, and some twin registries maintain impressively high retention rates over the years (e.g., The National Longitudinal Study of Adolescent Health).
Those readers wishing to establish new twin studies would do well to take note of some of the ingenious methods of recruiting: from the traditional media, birth records, immunization and other citizens’ registries, schools, websites, voter records, military records, hospitals, twin clubs, twin mothers’ associations, and even in the cases of the University of Washington Twin Registry and the California Twin Program, through the Department of Motor Vehicles. One population-based cohort used a ‘negative consent’ process, treating no response to a mail-out as a positive response and releasing information unless families actively opted out (Colorado Twin Registry). Other studies offered free zygosity tests (e.g., PETS, HealthTwiSt). A variety of methods were used to minimize attrition rates, through newsletters, mail-outs, and even social media (e.g., the Young Netherlands Twin Register). The Vietnam Era Twins Registry also set minimal ‘respite periods’ between visits and involved twins themselves in the planning of research topics.
While the majority of studies featured in this special issue focused on behavioral, psychiatric, and cognitive phenotypes, other well-studied areas include growth and development (Tokyo Twin Database; the Netherlands Twin Registry; the Quebec Newborn Twin Study); common physical diseases and their antecedents (the Chinese National Twin Registry, Twin Registry of Guinea-Bissau; Hungarian Twin Registry; the Norwegian Twin Registry; Vietnam Era Twins Registry); aging (Danish Twin Registry, TwinsUK, Italian Twin Registry); and cancer (the Cuban Twin Registry; the International Twin Study of Cancer and Chronic Disease). Specialist topics include dentition (the Australian study of genetic, epigenetic and environmental influences on dentofacial structures and oral health), eyesight (Australian genetic studies into ophthalmic traits; the Guangzhou Twin Project), sexuality (Finnish study), physical activity (Twin Research in Portugal), fingerprints (the Thai Twin Registry), and drug metabolism and mutagen sensitivity (the Twin Research Registry at SRI International).
Most twin studies are now collecting biosamples from tissues such as blood, saliva, or the inner cheek and extracting DNA for genetic studies. As technology has progressed, genetic studies are moving from a focus on individual genes to whole genomes, and some studies have started to use these tools. DNA can also be used for the study of epigenetics, which describes the molecular factors that influence gene activity without changing primary DNA sequence, and which are stable but environmentally changeable. Epigenetic factors are beginning to explain some of the phenotypic discordance within monozygotic (MZ) twin pairs, and registries are either conducting (e.g., PETS, International Twin Study, and California Twin Program) or planning to conduct (e.g., Guangzhou Twin Project and Sri Lankan Twin Registry) such studies. Some twin registries are studying the effects of specific non-shared environments such as those encountered in utero, to begin to explain phenotypic differences within twin pairs (e.g., the East Flanders Prospective Twin Survey, the Peri/Postnatal Epigenetic Twin Study).
Finally, we return to the age-old question of how best to determine zygosity. A bewildering array of questionnaires is currently in use, based around questions about whether twins have ever been confused by others. For a definitive answer, many registries use genetic testing on genetically highly variable regions, but again there are many specific methods cited. Perhaps it is time for a consensus on this. What should also go hand in hand with recoding of zygosity is chorionicity, especially because it has been associated with pre- or perinatal mortality and postnatal morbidity (Derom et al., Reference Derom, Bryan, Derom, Keith and Vlietnick2001). However, data on chorionicity are not easy to collect retrospectively, and even assessment pre- or postnatally is a highly skilled process. Knowledge of this skill needs to be spread more widely.
We hope you enjoy reading about the studies in this issue as much as we have.
