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.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East-Flanders, Belgium. It has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are ascertained at birth; basic perinatal data are recorded; chorion type and zygosity are established; and since 1969 placental biopsies have been taken and frozen at −20°C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of three subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early, before the fourth day after fertilisation), the monochorionic-diamnionic pairs (intermediate, between the fourth and the seventh day post fertilisation), and the monochorionic-monoamnionic pairs (late, after the eight day post fertilisation). This added a new dimension to didymology (the science of twins; διδυμоσ= twins): the timing of twinning. Studies can be initiated on primary biases, those originating “in utero”. Such studies may throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene-environment interactions as far as intrauterine environment is concerned, to name but a few.

The UBC Twin Project is an on-going study of personality and personality disorder that has collected personality data on approximately 1000 adult volunteer twin pairs. The primary purpose of the study is to develop and validate measures of the major forms of personality disorder as a quantitative alternative to the classificatory system first proposed by the DSM-III using the standard methods of personality and behavioural genetics research. To date, the study has explored the univariate and multivariate relationships between the major personality and personality disorder inventories, and their relationships to other psychopathologies including the mood and anxiety disorders and key psychological variables, such as cognitive ability, attachment and attitudes. The results have several implications for personality and personality disorders, most notably a rationalized diagnostic/nosological system to enhanced measurement instruments that index and reflect the influence of specific genetic and environmental influences.

Twins, due to their unique genetic and environmental relationships, have provided crucial insight in our understanding of genetic contributions to numerous etiologically complex disorders in developed countries. As the leading cause of death and adult disability, cardio- and cerebrovascular diseases are common in China, followed by cancer. Obesity and psychological disorders are increasing. The overall goal of this program is to develop a resource for genetic epidemiologic studies of these and other common and complex diseases in China. Our initial focus is to delineate the genetic and environmental determinants of vascular diseases in general, coronary artery disease (CAD) and stroke in particular. To date, we have over 4500 twin pairs registered and about 700 twin pairs studied for various metabolic traits (e.g., lipids, glucose, insulin, etc.). The long-term plan of this program is to (1) establish a population-based twin registry from several selected regions in China for future studies of specific common complex diseases; (2) conduct detailed phenotyping for clinical and intermediate traits related to cardiovascular diseases; (3) expand studies of twins to twin families by including their parents, siblings, and offspring for genetic linkage and association studies; and (4) follow up twins in the registry longitudinally. The goals of the program are health education and promotion of healthy behavior, early identification of cases to provide timely medical attention, and the evaluation of long-term effects of identified risk factors. We want to develop collaborations with investigators who have expertise in cancer, psychological disorders, and other disease areas.

The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954 by ascertainment of twins born from 1870 to 1910. During a number of studies birth cohorts have been added to the register, and by the recent addition of birth cohorts from 1931 to 1952 the Registry now comprizes 127 birth cohorts of twins from 1870 to 1996, with a total of more than 65,000 twin pairs included. In all cohorts the ascertainment has been population-based and independent of the traits studied, although different procedures of ascertainment have been employed. In the oldest cohorts only twin pairs with both twins surviving to age 6 have been included while from 1931 all ascertained twins are included. The completeness of the ascertainment after adjustment for infant mortality is high, with approximately 90% ascertained up to 1968, and complete ascertainment of all liveborn twin pairs since 1968.

The Danish Twin Registry is used as a source for large studies on genetic influence on aging and age-related health problems, normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, and clinical studies of specific diseases. The combination of survey data with data obtained by linkage to national health related registers enables follow-up studies both of the general twin population and of twins from clinical studies.

In studies on the Finnish Twin Cohort, we investigate genetic and environmental determinants of common, complex diseases, and their behavioral risk factors in Finland, a genetically unique and culturally homogenous population. We have formed the following databases: 1) Like-sexed twin pairs (13,888 pairs of known zygosity) form the older Twin Cohort. They have participated since 1975 in mail surveys, in clinical examinations for subsamples, and have been followed-up for morbidity using national medical registers; 2) The older Twin Cohort was expanded in 1996 to include opposite-sex pairs born 1938–1957 (c. 8000 pairs); 3) Two, new longitudinal studies of adolescent twins and their families, form a complementary, ongoing study base described in more detail in an accompanying article. Genetic and environmental effects vary over the life-span, and only longitudinal studies in genetically informative data sets permits the evaluation of such effects. Finally, the inclusion of DNA-based genetic information in a phenotypically rich family data base will offer a unique resource for research in genetic epidemiology and behavioral medicine.

Family, twin and adoption studies have provided evidence for familial and genetic influences on individual differences in disease risk and in human behavior. Attempts to identify individual genes accounting for these differences have not been outstandingly successful to date, and at best, known genes account for only a fraction of the familiality of most traits or diseases. More detailed knowledge of the dynamics of gene action and of specific environmental conditions are needed. Twin and twin-family studies with multiple measurements of risk factors and morbidity over time can permit a much more detailed assessment of the developmental dynamics of disease risk and the unfolding of behavioral risk factors.

The German Observational Study of Adult Twins (GOSAT) is the largest population-based observational twin study in Germany to date. Embedded in the Bielefeld Longitudinal Study of Adult Twins (BiLSAT), it addresses the etiology of personality, temperament and cognitive ability in a sample of 300 monozygotic (MZ) and dizygotic (DZ) adult twin pairs between 18 and 70 years of age. A major aim of the GOSAT lies in the utilization of different modes of measurement, (i.e., peer reports and observational data), in addition to self-reports which have been used predominantly in past behavioral genetic research on personality and temperament in adults. Participants completed a full day assessment at the University of Bielefeld including videotaped social interactions and presentations, psychometric intelligence tests and computerized elementary cognitive tasks as well as objective measures and unobtrusive behavior counts. The research design of the GOSAT was devised to reduce the potential impact of systematic rater bias on estimates of genetic and environmental influences to a minimum. In combination with extensive self-and peer report data on key personality and personality related dimensions available from the BiLSAT, the GOSAT provides a rich dataset, which currently includes DNA samples from 80% of its participants.

Two Italian twin registers are described, the Register of Italian Twin Athletes (RITA) and the Twin Register of Rome (TERRY), developed in recent years at the newly established University of Sport and Movement Sciences of Rome-Foro Italico (IUSM). Ascertainment procedures, database, applications and current prospects are outlined, along with their research focus, which mainly consists of epidemiological and clinical research on the determinants of sport performance as well as on the role of genetic factors versus lifestyle, especially physical activity, in health and aging.

The unique opportunity given by the “fiscal code”, an alphanumeric identification with demographic information on any single person residing in Italy, introduced in 1976 by the Ministry of Finance, allowed a database of all potential Italian twins to be created. This database contains up to now name, surname, date and place of birth and home address of about 1,300,000 “possible twins”. Even thought we estimated an excess of 40% of pseudo-twins, this still is the world's largest twin population ever collected. The database of possible twins is currently used in population-based studies on multiple sclerosis, Alzheimer's disease, celiac disease, and type 1 diabetes. A system is currently being developed for linking the database with data from mortality and cancer registries. In 2001, the Italian Government, through the Ministry of Health, financed a broad national research program on twin studies, including the establishment of a national twin registry. Among all the possible twins, a sample of 500,000 individuals are going to be contacted and we expect to enrol around 120,000 real twin pairs in a formal Twin Registry. According to available financial resources, a sub sample of the enrolled population will be asked to donate DNA. A biological bank from twins will be then implemented, guaranteeing information on future etiological questions regarding genetic and modifiable factors for physical impairment and disability, cancers, cardiovascular diseases and other age related chronic illnesses.

We describe subject recruitment and research results from the Osaka University Aged Twin Registry (OUATR). The research focus of OUATR is the genetic and environmental contributions to physical-cognitive-mental aging which we examined in Japanese twins in later adulthood. Within this large-scale registry (12,000 pairs) of oriental twins born between 1900 and 1935, approximately 10% of participants are MZ twins reared apart from early childhood. Two hundred and fifty pairs have had comprehensive medical examinations, including various blood chemical panels, lymphocyte subtests, WAIS (Wechsler Adult Intelligence Scale), and urine analysis. The future foci of this study are primarily on longevity, decline of cognitive functions with aging, bio-physiological functions, lifestyle and behavior genetics, and psycho-spiritual functions.

The Seoul Twin Family Study seeks to investigate genetic and environmental influences on the development of cognitive abilities and other psychological traits among children and adolescents in Seoul, South Korea. In November, 2001 with the assistance of the Seoul Metropolitan Office of Education, we began to solicit all private and public schools in Seoul to obtain names, addresses, and telephone numbers of the twins enrolled in schools in Seoul. The vast majority of the recruited twins were between 6 and 18 years old. The recruited twins and their non-twin siblings and parents will undergo comprehensive assessment of cognitive abilities, interests, daily activities, personality, and familial and non-familial environments. We plan to reassess the twins and their families every two years as the twins progress through major changes that characterize childhood, adolescence, and adulthood. In addition, medical records of the twins during the prenatal period will be examined to determine the effects of intrauterine environment on individual differences in cognitive abilities and other psychological traits. We also plan to undertake molecular genetic studies to identify genes involved in specific cognitive abilities.

The Korean Twin Registry is the first nationwide twin study in Korea. We compiled 154,783 twin pairs from existing nationwide data sources, mainly from address and national health insurance data. The coverage of this registry was almost complete for the twins born since 1970, but less complete as age increased, so that there were only 990 pairs who were born before 1930. The twins' health examination (N = 54,390 persons) and questionnaire (N = 44,546 persons) results were incorporated into the registry, yielding 12,894 and 9074 concordantly informative pairs. Morbidity and mortality outcomes have been followed up since 1990, for most diseases. For preliminary analysis of complex diseases, we selected ventricular septal defects (VSD) in young twins, stomach and colorectal cancers in adult twins. We identified 353 VSDs, 284 stomach cancers, and 116 colorectal cancers among twins. The prevalence rates of cancers, but not that of VSD, were lower in twins than those in population. The difference in the cancer prevalence was marked for twins born before 1926, implying some degree of selection. Like-sex (LS) twins showed familial recurrence risks (λLS) of 41.2 for VSD and 22.4 for colorectal cancers, and 1.74 for stomach cancers. For opposite-sex (OS) twins, we could estimate λOS of 19.8 for VSD only. These results were compatible with previous studies for VSD and colorectal cancers, but not for stomach cancers. Despite the strength in size, availability of health outcomes, and some lifestyle and basic laboratory data, we need accurate zygosity information to improve the validity of the results.

In 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a questionnaire at registration and afterwards when the children are 2, 3, 5, 7, 10 and 12 years of age. Teachers are asked to rate the behavior of the children at ages 7, 10 and 12 years. Adolescent and young-adult twins were recruited through City Councils in the early 1990s. These twins, their parents and siblings participate in longitudinal survey studies that include items about health, fertility, lifestyle, addiction, personality and psychopathology, religion, socioeconomic status, and educational attainment. The total number of twins and multiples registered with the NTR is currently over 60,000. Subgroups of twins and siblings take part in studies of cognitive development, brain function and neuropsychological indices of attention processes, and molecular genetic studies of classical and behavioral cardiovascular risk factors. DNA samples are currently collected in selected twin families for two large linkage studies, which aim to find QTLs for anxious depression and for nicotine addiction. Sisters who are mothers of DZ twins contribute DNA samples for a linkage study of DZ twinning. Large cohorts of phenotyped family members from the general population are very valuable for genetic epidemiological studies and permit selection of informative families for gene finding studies.

The Norwegian Twin Registers include several sets of population-based sub-registers, and covers twin pairs born between 1895 and today. Except for the missing birth years 1960 to 1967, the register is almost complete. Most of the register contains information about both same-sexed and opposite-sexed twin pairs, except for twin pairs born between 1946 and 1960, where only same-sexed twins are registered. In a substantial part of the register, information about zygosity is obtained, mainly by a mailed questionnaire and in some cases supported by DNA testing. These are the birth years 1915 to 1960 and the birth years 1967 to 1979. Zygosity information is further obtained in the different twin studies derived from the twin register. In 1990 the whole register was made available in a computerized form. Several twin studies have been derived from the different parts of the register. In this article, studies from the two earliest parts of the register are reviewed and grouped by recruitment specifics. Finally, future plans for the register and twin studies are discussed.

The Norwegian Institute of Public Health in Oslo has an ongoing program of twin research using population-based cohorts of twins. The current database includes information on twins identified through the Medical Birth Registry of Norway and born from 1967–1979, altogether 15,370 twins. This is a longitudinal study with a cohort sequential design whereby new cohorts are recruited into the study at 5–6 year intervals. Sub-samples of these twins have participated in questionnaire studies and clinical assessment sub-projects. These projects include national and international collaborations. Our primary areas of interest include mental health and psychological well-being, obesity, asthma and allergies, health behaviors and health perceptions, comorbidity, and perinatal influences on health outcomes. This paper provides a brief overview of the data, sample, and the various research projects associated with this twin program of research.

Sri Lanka is an island with genetic diversity between the five main population groups. Our twin registry is the first in the developing world. Initially, we established a volunteer cohort of 4600 twin pairs through a competition advertised in the media. In addition, we have volunteer cohorts, birth registration-based cohorts through hospitals, and community-based cohorts. There is also a nationwide population-based younger twin cohort (1992–1997) traced through the Department of Birth and Death Registration. Additionally, we have adapted a Zygosity determination questionnaire and validated it. Establishing ethical guidelines for twin research was a priority because the field of bio-ethics is at an early stage of development in Sri Lanka. These guidelines were from a developing world perspective. A sister organization, the Multiple Birth Foundation, was formed to cater to twins and their special needs and to represent their interests, and several branches have been formed. We intend to build capacity by establishing a genetic lab and through crosscultural collaboration. Our vision is to establish a multidisciplinary research foundation. Based on our research findings, we plan to build services to cater to needs of twins by working with professionals, statutory services and government policy makers.

Since the Swedish Twin Registry was first established in the late 1950s to study the importance of smoking and alcohol consumption on cancer and cardiovascular diseases, it has been expanded and updated on several occasions. The focus has similarly broadened to most common complex diseases. The content of the database is described, ongoing projects based on the registry are summarized, and we review some of the principal findings on aging, cancer and cardiovascular disease that have come from the registry. Ongoing efforts and future plans for the STR are discussed. Among others, we plan blood collection and genotyping to study the genetic bases of complex diseases, a first contact ever with the cohorts born after 1958, and in-depth studies of selected diseases, such as Parkinson’s disease and chronic fatigue syndrome.