The Minnesota Twin Registry: current status and future directions.

The Minnesota Twin Registry is a birth-record-based twin registry. Begun in 1983, it includes data for 4307 surviving intact pairs born in Minnesota between 1936 and 1955. In addition, the Registry includes 901 twin pairs born in Minnesota from 1904 to 1934, as well as 391 male pairs born in Minnesota from 1961 to 1964. The research focus is primarily on human individual differences assessed by self-report. Questionnaires completed by the participants include measures of personality, occupational interests, demographics, and leisure-time activities. We outline major contributions that have resulted from Registry research, as well as current and future research directions.     

The Australian Twin Registry.

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 Mid-Atlantic Twin Registry.

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of twin pairs ascertained from birth records and school system records of Virginia, North Carolina, and South Carolina. The MATR was formed in 1997 with the merging of the Virginia and North Carolina Twin Registries, and it expanded to include South Carolina when access to twin birth records in that state was granted in 1998. Registered twins ("participants") number more than 51,000, with approximately 46,000 of these individuals representing complete pairs. Roughly two-thirds of MATR participants are over age 18, with a mean age of approximately 35 years. These participants have primarily been drawn from the more than 170,000 identical and fraternal twin pairs born in the three states between 1913 and 2000. Twins and their family members have participated in numerous research projects, ranging from general health surveys to studies on specific health topics such as cardiovascular disease; depression and anxiety; seizures; behavioral development; pregnancy complications; conduct disorder; drug use, abuse, and dependence; cleft lip/palate; obesity; and chronic fatigue syndrome. The MATR has established a privacy policy and strict standard operating procedures to protect the confidentiality of participant data. The MATR considers a limited number of qualified requests per year from investigators interested in recruiting MATR participants into their research studies.     

Potential bias regarding birth weight in historical and contemporary twin data bases.

In this study we examine the hypothesis that monozygotic (MZ) twins in historical databases are less discordant for birth weight due to negative selection of severely discordant MZ twins. Furthermore, we test the hypothesis that MZ twins are less discordant for birth weight when comparing a volunteer based twin registry with a population based twin registry, due to selective registration. Data were available on 3927 twin pairs from the volunteer Australian Twin Registry born before 1964, 3059 volunteer twin pairs from the Netherlands Twin Register born 1987-1989 and 454 Belgian twin pairs from The East Flanders Prospective Twin Survey born 1987-1989. Intrapair relative birth weight differences (RBWD) were computed for MZ and dizygotic (DZ) twins from each twin registry. Comparing birth weight differences between MZ and DZ twins provides support for the hypothesis that MZ twins are subject to a negative selection in historical databases. Furthermore, Australian MZ twins have a lower RBWD compared to Dutch MZ twins when corrected for the RBWD of Australian and Dutch DZ twins, indicating circumstances which only affect MZ twins. Our hypothesis that MZ twins are less discordant for birth weight in a volunteer based twin registry compared to a population based twin registry had to be rejected. We suggest that investigators using historical databases to test the fetal origins hypothesis should be aware of this increased likelihood of selective exclusion of individuals with extreme morphometric parameters at time of birth.     

The Danish Twin Registry: 127 birth cohorts of twins.

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.     

Chinese National Twin Registry as a resource for genetic epidemiologic studies of common and complex diseases in China.

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.     

Are heritability estimates generalizable? Lack of evidence from cross-sample correlations

The majority of research indicates that estimates of heritability are not generalizable beyond the specific sample on which they have been calculated. This research has been limited, however, in its scope. The present set of investigations center upon an examination of previously reported heritability estimates for the scales of the Minnesota Multiphasic Personality Inventory (MMPI). The first investigation correlates the estimates for eight samples derived from a variety of published studies. The second investigated correlates the DZ twin pair and MZ twin pair intraclass correlations from four of the first investigation's samples. The third investigation correlates the estimates from one study in which the same sample was tested twice over a period of less than five years. It is concluded that no evidence is available for the generalizability of these estimates of MMPI scale heritability either across samples or even across time with the same sample.     

The Italian Twin Project: from the personal identification number to a national twin registry.

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 though 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.     

Modulators of neuronal migration and neurite growth.

A multitude of molecules have been identified over the past few years that promote neurite outgrowth in vitro. The concept that these molecules work mainly by providing an adhesive surface for neuronal growth cones has been challenged by evidence from recent experiments. Some of the substrate molecules have diverse actions on cell migration and neurite growth. In addition, there is now evidence that there are molecules that specifically inhibit growth cone locomotion. This has given rise to the hypothesis that growth cones integrate a variety of growth-promoting and inhibitory signals and translate them into directed locomotion.     

Sri Lankan Twin Registry.

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.     

Preschool social and cognitive behaviors: the Southern Illinois Twins.

The Southern Illinois Twins registry consists of a small group of twins from the southern Illinois area and some areas in Missouri and Kentucky, as well as siblings of twins and singletons who have been involved in the study. The current project has as its primary focus the identification of variables that predict aggressive and prosocial behaviors in preschoolers, especially to explore the etiology of individual differences in aggressive and prosocial behaviors from a behavior genetic perspective. Twins are tested yearly within months of their birthdays, from ages 1 year to 5 years. Siblings are tested at 5 years of age. At ages 1-4 years, children are tested on a cognitive battery and mother-child interactions are videotaped. At 5 years, children engage in a peer play situation in the lab. Results thus far suggest that aggression during play in the lab shows genetic influence, corroborating earlier parent rating studies.     

The Vietnam Era Twin Registry.

The Vietnam Era Twin (VET) Registry is composed of 7369 middle-aged male-male twin pairs both of whom served in the military during the time of the Vietnam conflict (1965-1975). The Registry is a United States Department of Veterans Affairs resource that was originally constructed from military records; the Registry has been in existence for more than 15 years. It is one of the largest national twin registries in the US and currently has subjects living in all 50 states. Initially formed to address questions about the long-term health effects of service in Vietnam the Registry has evolved into a resource for genetic epidemiologic studies of mental and physical health conditions. The management and administration of the VET Registry is described with particular attention given to the processes involved with database maintenance and study coordination. Several waves of mail and telephone surveys have collected a wealth of health-related information on Registry twins. More recent data collection efforts have focused on specific sets of twin pairs and conducted detailed clinical or laboratory testing. New Registry initiatives for the future include the construction of a web site and the development of a DNA repository.     

Birth wantedness reports: A look forward and a look back

Abstract

The majority of research indicates that estimates of heritability are not generalizable beyond the specific sample on which they have been calculated. This research has been limited, however, in its scope. The present set of investigations center upon an examination of previously reported heritability estimates for the scales of the Minnesota Multiphasic Personality Inventory (MMPI). The first investigation correlates the estimates for eight samples derived from a variety of published studies. The second investigation correlates the DZ twin pair and MZ twin pair intraclass correlations from four of the first investigation's samples. The third investigation correlates the estimates from one study in which the same sample was tested twice over a period of less than five years. It is concluded that no evidence is available for the generalizability of these estimates of MMPI scale heritability either across samples or even across time with the same sample.     

Genes controlling expression of defense responses in Arabidopsis--2001 status.

In the past two years, the focus of studies of the genes controlling expression of defense responses in Arabidopsis has shifted from the identification of mutants to gene isolation and the ordering of genes within branches of the signal transduction networks. It is now clear that gene-for-gene resistance can be mediated through at least three genetically distinguishable pathways. Additional genes affecting salicylic-acid-dependent signaling have been identified, and double-mutant analyses have begun to reveal the order in which they act. Genes required for jasmonic-acid-dependent signaling and for induced systemic resistance have also been identified.     

The Swedish Twin Registry in the third millennium.

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.     

Twinning rates in Ghana.

The incidence of twin births in Accra and Kumasi, the two major cities in Ghana, was investigated. In Accra, data were collected from the Korle-Bu Teaching Hospital while data were collected and analyzed from the Komfo Anokye Teaching Hospital in Kumasi. Both hospitals are the leading teaching hospitals in Ghana. The data consisted mainly of single and twin births recorded in the hospitals over a period of 12 years in Accra (1988-1999) and 15 years in Kumasi (1985-1999). The study revealed an incidence of 33.4 twin births per thousand live births for Accra and 26.6 twin births per thousand live births for Kumasi. Though these values are not as high as those reported among the Yoruba tribe of southwest Nigeria, who are reported to have the highest twin birth rates in the world, the present values still rank among the highest recorded twin birth rates.     

The Korean Twin Registry--methods, current stage, and interim results.

The Korean Twin Registry is the first nationwide twin study in Korea. We compiled 154,783 twin pairs from existing nation-wide 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 (lambdaLS) 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 lambdaOS 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.     

Intrauterine growth restriction in like-sex twins discordant for structural defects

BACKGROUND: An increased risk for intrauterine growth restriction in the affected member of like-sex twin pairs discordant for hypospadias has been reported. The purpose of this study was to document patterns of birth weight disparities in like-sex twins discordant for a variety of structural defects in order to determine if this is a general phenomenon seen in twins who are discordant for any malformation, is seen only in pairs discordant for certain specific malformations, or is unique to hypospadias. METHODS: Data were extracted from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Between 1967 and 1999, all like-sex twin pairs discordant for hypospadias or any other isolated defect that met the criteria of at least 5 discordant pairs for which birth weight was available on both twins were selected. All nonmalformed like-sex twin pairs in the ECLAMC data base collected over the same study years were selected as controls. RESULTS: A total of 216 discordant malformed like-sex twin pairs in 13 defect categories and 328 nonmalformed like-sex twin pairs met the criteria for inclusion. The proportion of affected infants who were > or =20% smaller than their co-twin was statistically significantly different from controls for hypospadias, heart defects, anencephaly, and esophageal atresia. CONCLUSIONS: Intrauterine growth restriction seen in the affected member of like-sex twin pairs discordant for hypospadias is not unique, but occurs as well in at least 3 additional structural malformations.     

Eukaryotic DNA replication.

The past decade has witnessed an exciting evolution in our understanding of eukaryotic DNA replication at the molecular level. Progress has been particularly rapid within the last few years due to the convergence of research on a variety of cell types, from yeast to human, encompassing disciplines ranging from clinical immunology to the molecular biology of viruses. New eukaryotic DNA replicases and accessory proteins have been purified and characterized, and some have been cloned and sequenced. In vitro systems for the replication of viral DNA have been developed, allowing the identification and purification of several mammalian replication proteins. In this review we focus on DNA polymerases alpha and delta and the polymerase accessory proteins, their physical and functional properties, as well as their roles in eukaryotic DNA replication.     

The St. Thomas' UK Adult Twin Registry.

The Registry consists of nearly 10,000 monozygous and dizygous adult caucasian twins aged 18-80 from all over the UK and was started in 1993. This is a volunteer sample recruited by successive media campaigns without selecting for particular diseases or traits. All twins receive a series of disease questionnaires. In addition over half the twins have been assessed in detail clinically for several hundred phenotypes related to common diseases or intermediate traits. The focus has been primarily on cardiovascular, metabolic, musculoskeletal, dermatological, and opthalmological diseases. Over 3000 DZ twins have had a genome wide scan performed as well as many candidate genes allowing both linkage and association studies. The registry has led to many successful innovative research projects, particularly in common diseases previously thought to be predominantly environmental and helped positionally clone some novel genes for common diseases.