The 75 Years of Innovation series highlights the groundbreaking innovations spanning from SRI’s founding in 1946 to today. Each week, SRI will release an innovation, leading up to its 75th anniversary in November 2021.
The Twin Research Registry is a community registry of identical and fraternal twins to help in research into diseases, traits and behaviors
Seeing double: The work at SRI to develop a Twin Research Registry
The birth rate of twins in the U.S. in 2019 was 32.1 per 1,000 live births. Of these twins, 2/3 are fraternal (with different DNA), and 1/3 are identical (having the same DNA). Because identical twins share 100% of their DNA code, researchers can explore the role that genetics plays in human development, behaviors, diseases and other traits. As such, twin studies or twin research has provided a way to explore the nature vs. nurture argument.
To perform these studies, scientists need access to data on twins. To help facilitate scientific research on twins, SRI International established the Twin Research Registry (TRR).
What is the Twin Research Registry (TRR)?
SRI researchers use twin studies as a tool to determine genetic influence. A 1992 paper published by SRI on exploring the genetics of smoking was made possible by access to a National Academy of Sciences/National Research Council (NAS-NRC) Twin Registry that had information on 15,924 white male twin pairs born between 1917–1927 and who served in the armed forces. The registry allowed SRI researchers to study possible genetic effects as a result of tobacco smoking and the co-occurrence of other substance use, such as alcohol.
In 1995, SRI decided to create a more comprehensive study sample of twins. SRI created a widespread advertising campaign across TV and other media in the San Francisco Bay area. This campaign reached out to twins, asking for their help in scientific research. The result was a community-based registry, the Twin Research Registry (TRR). In 2019, SRI transferred the TRR into the hands of Stanford Medicine; at that point, there were 6,208 individual twins in the registry.
Testing twins’ zygosity
The TRR uses a questionnaire to help establish the zygosity (degree of DNA similarity) of participating twins.
There are two confirmed types of twins:
● Monozygotic (MZ), or identical twins, share 100% of their genes
● Dizygotic (DZ), or fraternal twins, share 50% of their genes
The questionnaire asks several key questions to establish the twins’ relationship, including:
- As far as you know, are you and your twin: fraternal, identical or don’t know?
- During your entire life, how close do you feel that you and your twin have been compared with your impression of closeness between ordinary siblings: less close, as close as, somewhat closer, or much closer than ordinary siblings?
- How far in miles do you live from your twin now?
- How frequently do you and your twin get together now?
The most recent version of the TRR uses a classification algorithm to assign a weight to responses to further questions on physical similarity, whether parents, teachers or strangers ever mistook one twin for the other, self-reported zygosity, etc. The resulting data is compiled in the registry and made available to researchers studying twins.
Types of research carried out in twin studies
Imagine if one twin develops a disease; would the other develop the same disease? What if that disease was associated with an environmental factor? Twin studies use the shared genetics of twins to explore possible inherited components of diseases, traits and behaviors. Put simply, during a twin study, the likelihood of a twin developing the same disease, trait, etc., is compared between MZ and DZ twins. If the trait is more likely to be shared by MZ twins than DZ twins, this points to an underlying genetic factor. If MZ and DZ twins show a similar frequency of a given trait, this points to environmental influences. Some examples of research studies that have been carried out using the TRR include:
Pharmacokinetics of Nicotine in Twins: This study examined 139 pairs of twins (110 MZ and 29 DZ). Researchers looked at how the body metabolizes nicotine and cotinine, examining the genetic and environmental factors of nicotine dependence and the effectiveness of treatment.
Sensitivity to mutagens as a cancer indicator: A study involving 148 pairs of MZ twins, 57 pairs of DZ twins, and 50 non-twin siblings, compared peripheral blood lymphocytes to measure mutagen sensitivity. Mutagen sensitivity was tested as an indicator for cancer risk and showed high heritability.
T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals: A study involving 21 pairs of MZ twins ranging from 9 to 76 years old. Pairs of twins in which only one had asthma (and the other did not) were considered. The twin data allowed researchers to determine if modifications in T cells were associated with environmental factors (such as exposure to secondhand smoke) or genetic.
Stanford Medicine continues to request the help of twins in research. Registration is online for twins of all types and all ages for consideration for research studies.
Resources
CDC, Multiple Births: https://www.cdc.gov/nchs/fastats/multiple.htm
Carmelli D, Swan GE, Robinette D, Fabsitz R. Genetic influence on smoking — a study of male twins. N Engl J Med. 1992 Sep 17;327(12):829–33. doi: 10.1056/NEJM199209173271201. PMID: 1508241.
Stanford Medicine, Twin Registry: https://med.stanford.edu/twin-registry/about.html
Innovation: https://www.sri.com/hoi/twin-research/
SRI, The Dish, Want to know if it’s nature or nurture? Look at twins: https://medium.com/dish/want-to-know-if-its-nature-or-nurture-look-at-twins-409f02626bfc
Stanford Medicine Twin Registry registration: https://med.stanford.edu/twin-registry/participate.html
Swan GE, Benowitz NL, Jacob P 3rd, Lessov CN, Tyndale RF, Wilhelmsen K, Krasnow RE, McElroy MR, Moore SE, Wambach M. Pharmacogenetics of nicotine metabolism in twins: methods and procedures. Twin Res. 2004 Oct;7(5):435–48. doi: 10.1375/1369052042335269. PMID: 15527659.
Wu, X., Spitz, M. R., Amos, C. I., Lin, J., Shao, L., Gu, J., Swan, G. E. (2006). Mutagen sensitivity has high heritability: Evidence from a twin study. Cancer Research, 66, 5993–5996.
Runyon, R., Rajeshuni, N., Cachola, L., Swan, G. E., &Nadeau, K. (2012). The effects of smoking on the immune response: Gene methylation and T-cell-based responses in twins discordant for smoking. American Journal of Respiratory Critical Care Medicine, 185, A3878.
