National Twin Registry
Twin studies are considered to be the gold standard for investigating the relative importance of genetic susceptibility and environmental influences to the development of complex traits and diseases in human populations. The use of twins can significantly enhance the statistical power of a genetic study by limiting the amount of genetic and/or environmental variability. Monozygotic (MZ) twins share all their genes and dizygotic (DZ) twin pairs, on average, share about 50% of their segregating genes. Both types of twin pairs often share similar pre- and post-natal environments as well. By determining the concordance rates for a disease or trait among MZ and DZ twin pairs, we can ascertain whether the risk factors for that disease or trait are hereditary, environmental, or some combination of these. Furthermore, with structural equation modeling and multivariate analyses of quantitative twin data, we can measure the extent to which allelic variants and environment influence phenotypic traits.
While the use of twins can reduce the sample size needed in a genetic study (by increasing the statistical power), large numbers of twins are still required when complex or rare diseases are involved. Existing twin registries or combinations of them are inadequate to conduct large, in-depth studies with sufficient statistical power, especially if potential confounding or the disease prevalence dictates stratification based on gender, ethnicity, age or other factors. The purpose of this study, therefore, is to comprehensively review and report on the current and projected status of the twins in the U.S. and determine the feasibility of establishing a national, population based twin registry similar to those that already exist in other countries (Sweden, Denmark, Finland, Australia, Sri Lanka and the United Kingdom).
Other Twin Registries in the U.S.
While national, population-based twin registries are quite common in other countries, twin registries in the U.S. are few, and limited in sample size and diversity. Currently, the largest U.S. twin registry is the Mid-Atlantic Twin Registry (MATR) at the Virginia Commonwealth University. Registered participants number more than 51,000 with approximately 46,000 of these representing intact twin pairs. The ethnic makeup of the registry is about 70% Caucasian, 20% African-American, and less than 5% Hispanic and others. MATR twins and their family members have participated in numerous research projects ranging from general health surveys to studies on specific conditions such as cardiovascular disease, depression and anxiety, seizures, behavioral development, pregnancy complications, cleft lip/palate, obesity, chronic fatigue syndrome and many others.
The second largest twin registry in the U.S. is the National Academy of Sciences/National Research Council World War II Veteran Twin Registry (NRCWWIIVTR). This registry is composed of over 15,000 white male twin pairs, ranging from 73 to 83 years old. Approximately half of these pairs are no longer intact due to co-twin deaths. Other veteran based registries exist (Vietnam Era Twin or VET Registry) but these are also limited in diversity; the VET registry is composed of only older (middle-aged) male pairs. This registry was established to address the long term health effects due to service in Vietnam but has evolved to other mental and physical health problems.
Objectives of the National Twin Registry Feasibility Study
The Program in Clinical Research therefore, is conducting a feasibility study for establishing a National Twin Registry in the U.S. and three disease specific registries for twins with type 1 diabetes mellitus (DM), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). More specific objectives of this feasibility study are to:
- Evaluate the ethical, legal and social issues in establishing twin registries
- Estimate the willingness of twins to enroll in a national twin program
- Investigate alternatives to twin registries
- Devise optimum ascertainment and retention methods
- Devise ascertainment and recruitment methods for populations with historically low recruitment rates
- Conduct cost-benefit analyses