THE STANFORD TWIN REGISTRY

The SRI TRR had a long history of collaborating with investigators at Stanford. Previous SRI research studies done in collaboration with Stanford University include a longitudinal study to better understand the genetic components of the body’s immune response to the flu vaccine, another study to look at the which aspects of the immune response to the shingles vaccine are due to genetics, an online survey about various aspects of health and immunity, a study to better understand the various ways the immune system responds to exposure to tobacco smoke, and a study to examine the genetic and familial aspects of pain sensitivity.

Origins of the Twin Research Registry (TRR)

Prior to the development of the TRR, investigators at the Center for Health Sciences at SRI International (formerly known as the Stanford Research Institute) had utilized the twin design to determine the relative proportion of environmental and genetic variance in survey-based and clinically measured phenotypes. Extending over 20 years, these studies were done in nationally-based twin registries including the National Academy of Sciences/National Research Council (NAS/NRC) World War II Twin Registry (Hrubec & Neel, 1978) and a more intensively studied subset of twins known as the NHLBI Twin Study (Feinleib et al., 1977).

In 1992, the SRI investigators published a paper based on a twin study of ever smoking, smoking quantity, and smoking cessation (Carmelli, Swan et al., 1992) in the New England Journal of Medicine. As a follow-up to this paper, Dr. Gary E. Swan and colleagues at SRI initiated the creation of the TRR in 1995 to develop a study sample of adult twins to support more in-depth studies of nicotine dependence and related phenotypes including nicotine metabolism.

Over the course of the ensuing 24 years, twins participated in research studies. Most participated in one study, but many participated in multiple studies: 275 participated in two, 76 participated in three, 53 participated in four, and 29 participated in five, and some even participated in as many as 6, 7, or 8 different research studies.  These studies were done in collaboration with scientists at the University of California Medical Center in San Francisco, the University of Texas MD Anderson Cancer Center, and the Stanford University School of Medicine. In addition to nicotine dependence and metabolism, clinical phenotypes studied include those related to mutagen sensitivity, pain response before and after administration of an opioid, and a variety of immunological responses to environmental exposures, including second-hand smoke and vaccination for seasonal influenza virus and Varicella zoster virus.

Relevance of the TRR to studies in immunolgy

The field of immunology is currently in a state of rapid discovery with the advent of understanding of the extent to which human immunological processes and mechanisms underlie common and rare conditions. Because the discovery of immunological markers of disease in humans is in its early stages, the extent to which many of these markers are influenced by genetic and/or environmental sources of variation remains to be determined. The use of the twin design is a cost-effective way to determine the relative proportion of genetic and environmental influences, both on the occurrence of conditions of known or suspected immunologic etiology as well as on biomarkers that are either associated with or predictive of these conditions (Krishnan et al., 2012).

Dr. Mark Davis and members of Stanford University Medical School’s Institute for Immunity, Transplantation, and Infection conducted a series of twin studies in collaboration with Dr. Swan (now at the Stanford Prevention Research Center). These projects have utilized MZ and DZ twin pairs from the TRR as a way to determine the relative contribution of genetic and environmental factors to innate and adaptive immunological responses to vaccination for seasonal influenza virus (‘Influenza Immunity: Protective Mechanisms Against Pandemic Respiratory Virus’, U19AI057229) and for Varicella zoster virus (‘Vaccination and Infection: Indicators of Immunological Health and Responsiveness’, U19AI090019).

Prior to transferring to Stanford, the SRI TRR had 6,208 active registered individual twins.  Of this number 4,960 were members of a twin pair, and 1,248 were single members (the co-twin did not register).  The registered members were mostly adult (91.3%) and female (69.5%), and over 50% reported living in California.  Adults who registered with the SRI TRR were more likely to be identical twins (71.4%) than fraternal twins (26.6%), with 1.9% indicating they did not know what type of twin they were.  For minors (under age 18), the proportions were different: 45.4% said they were identical, 49.4% said they were fraternal, and 5.1% did not know they type of twin they were.

Current status of the TRR

Because of the importance of twins to immunological research, the TRR now resides at the Institute for Immunity, Transplantation and Infection (ITI) in the Stanford School of Medicine.  To join the Stanford Twin Registry at ITI, each twin completes a registration form with basic demographic information either online at the TRR Web site. Contact is maintained with members by means of annual newsletters and various events. The managers of the TRR protect the confidentiality of twin data with established policies. No information is given to other researchers without prior permission from the twins. All methods and procedures are reviewed by an Institutional Review Board. Twins in the TRR have participated in studies of complex, clinically relevant phenotypes that would not be feasible to measure in larger samples.