The Brazilian Twin Registry (BTR) was established in 2013 as the first twin registry in Brazil and for that matter a decisive undertaking for twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits (Hopper, Reference Hopper1992). Being the first twin registry in South America, the BTR was set up to be a unique source of information on health and disease, providing the genetic and environmental profile of a region still under-represented and under-explored.
The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. Although Brazil does not have a long-standing tradition in twin research there are isolated groups of researchers who have conducted twin research previously, and we envisage that the BTR will be the central coordinator of other twin studies in the country.
A Brief History of the BTR
The BTR (www.gemeosbrasil.org) was born as a result of the interest of Brazilian researchers undertaking twin research in Australia, mainly in the field of musculoskeletal pain (Dario et al., Reference Dario, Ferreira, Refshauge, Sanchez-Romera, Luque-Suarez, Hopper and Ferreira2016; Ferreira et al., Reference Ferreira, Ferreira, Lam, Maher and Hopper2011; Ferreira et al., Reference Ferreira, Beckenkamp, Maher, Hopper and Ferreira2013; Ferreira et al., Reference Ferreira, Craig, Hopper and Carrick2016; Junqueira et al., Reference Junqueira, Ferreira, Refshauge, Maher, Hopper, Hancock and Ferreira2014; Oliveira et al., Reference Oliveira, Ferreira, Refshauge, Maher, Griffin, Hopper and Ferreira2015; Pinheiro et al., Reference Pinheiro, Ferreira, Refshauge, Colodro-Conde, Carrillo, Hopper and Ferreira2015). Since its inception, the BTR has been fully supported by the Australian Twin Registry and could be regarded as its co-twin registry. To our knowledge, the BTR is the only established active twin registry in South America, and the lack of a previous twin registry in the region led us to establish the registry through the implementation of a research project focused on risk factors for low back pain in the state of Minas Gerais, Brazil. The aim is to expand the research activities through the integration of other twin research groups in Brazil and broaden the scope of research co-ordinated by the BTR.
The BTR became a member of the International Network of Twin Registries in 2015 (Buchwald et al., Reference Buchwald, Kaprio, Hopper, Sung, Goldberg, Fortier and Harris2014). Currently, 291 twins have consented to be registered in the BTR, with baseline and demographic data available from 151 twins. One of the strengths of our implementation design is the availability of health and lifestyle data from the register-entry questionnaire. The current twin sample is younger than in most twin registries (mean age = 30; range = 18–83), and characteristics of the 151 twins include 64 pairs of monozygotic and 12 pairs of dizygotic twins (Table 1).
TABLE 1 Characteristics of 151 Twins With Baseline Data in the Brazilian Twin Registry (151 out of 291 Registered Twins)
Funding of the BTR
The BTR is funded by an enabling grant from the Brazilian agency CNPq, a people support scheme provided by the Brazilian agency CAPES, and an international research and research training fund from the University of Melbourne, Australia.
Recruitment
We are recruiting twins from a variety of sources, including media campaigns, social networking (e.g., Facebook), the BTR website, media appearances (e.g., TV, radio, national newspapers), multiple birth associations (e.g., Vizinhos de Utero), personal referrals, as well as healthcare providers and governmental databases.
Recruitment Through a Study of Low Back Pain
One of the main recruitment strategies we are using to register twins is through the invitation to participate in a longitudinal study investigating genetic and environmental factors for low back pain occurrence. This is the Brazilian arm of a large consortium study, with data also being collected in Australia. This study has been approved by the Local Human Research Ethics Committee at UFMG (protocol number 507231) and has received funding from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (project number A009_2013).
Study Population and Setting
All Brazilian twins aged ≥18 years old who comprehend Portuguese are eligible and are being invited to participate in the study. A number of separate invitation strategies are being adopted: (1) media campaigns in Brazilian universities, faculties, and other locals of interest, (2) media campaigns using social networking (e.g., Facebook), (3) media campaigns using the developed website of the project, and (4) local publicity and word-of-mouth. We expect a convenient sample of 300 Brazilian twin pairs (n = 600 individuals) to be recruited for the low back pain study, with twins being automatically registered with the BTR.
Twins who fulfill the inclusion criteria and agree to participate in the study are contacted by a study researcher to collect relevant data. Prior to the data collection, the researchers double-check the inclusion criteria and explain the nature of the study to the participant.
Data Collection at Baseline and Follow-Ups
The experience of the participants of low back pain and potential risk factors are investigated using our baseline questionnaire (Table 2). Participants may choose to answer the questionnaire in person, over the telephone, or electronically. At baseline, demographics, zygosity, anthropometrics, and health history of the participants are collected using standard self-reported questionnaires. Portuguese versions of the standard self-reported questionnaires are used. Data on health variables include the following: health-related quality of life, physical workload and physical activity level, lifestyle (e.g., smoking) and psychosocial (e.g., levels of social isolation) factors, and occurrence of health problems (e.g., low back pain).
TABLE 2 Assessed Phenotypes in the Brazilian Twin Registry
Note: Peas-in-a-Pod questionnaire: For twins under 18 years old, score ranges from 3 to 10, with scores up to 6 indicating monozygotic twins. For adults, both twins have to complete the questionnaire and their scores are added together to have a final score ranging from 6 to 20, with a score from 6 to 13 indicating monozygotic twins. EuroQol-5D-3L: Assess health-related quality of life in five dimensions (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analogue scale with endpoints of ‘best imaginable health state’ set at 100 and ‘worst imaginable health state’ at 0 to assess self-reported quality of life. Physical Workload Index: 19 items assess how often individuals stay in different work situations. Active Australia Survey: Assesses physical activity level over the last 7 days. Pittsburgh Sleep Quality Index: Score ranges from 0 to 21, with greater scores indicating worse sleep quality. CES-D Scale (Center for Epidemiological Studies-Depression Scale): Score ranges from 0 to 20, with greater scores indicating higher depressive symptoms. Friendship Scale: Score ranges from 0 to 24, with smaller scores indicating more isolation. Roland Morris Disability Questionnaire: Score ranges from 0 to 24, with greater scores indicating more disability related to low back pain. Visual Analogue Scale: Score ranges from 0 to 10, with greater scores indicating higher low back pain intensity.
The questionnaire used at baseline was developed by the study researchers and was based on the script used by other established registries (i.e., Australian Twin Registry and Spanish Murcia Twin Registry) in order to maintain consistency and future comparisons among populations. Factors collected have been previously reported in twin studies as being associated with low back pain (Ferreira et al., Reference Ferreira, Beckenkamp, Maher, Hopper and Ferreira2013; Hartvigsen & Christensen, Reference Hartvigsen and Christensen2007; Hartvigsen et al., Reference Hartvigsen, Frederiksen and Christensen2006; Hestbaek et al., Reference Hestbaek, Korsholm, Leboeuf-Yde, Kyvik, Hestbaek, Korsholm and Kyvik2008). Variables collected are assessed, as described below.
Demographics, Anthropometrics, and Social Variables
Demographics such as age, sex, and ethnicity are assessed by self-reported questions. Self-reported questions also assess anthropometrics (e.g., weight and height) and social variables (e.g., marital status, familiar income, educational level, and occupation).
Health History
Health-related quality of life is assessed using the EQ-5D (Rabin & de Charro, Reference Rabin and de Charro2001). Participants are asked to describe their own health according to five dimensions (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and also provide a self-rating on a visual analogue scale with endpoints of ‘best imaginable health state’ set at 100 and ‘worst imaginable health state’ at zero. Twins’ physical workload and physical activity level are assessed using, respectively, the Physical Workload Index (Hollmann et al., Reference Hollmann, Klimmer, Schmidt and Kylian1999) and the Active Australia Survey (Brown et al., Reference Brown, Trost, Bauman, Mummery and Owen2004). Self-reported questions assess lifestyle factors, including smoking, alcohol, and illicit drugs consumption. Sleep quality is assessed using the Pittsburgh Sleep Quality Index (Bertolazi et al., Reference Bertolazi, Fagondes, Hoff, Dartora, Miozzo, de Barba and Barreto2011). Anxiety and depression is assessed using the Center for Epidemiological Studies-Depression Scale (CES-D; Batistoni et al., Reference Batistoni, Neri and Cupertino2007), and participants’ perceived levels of social isolation is assessed using the Friendship Scale (Hawthorne et al., Reference Hawthorne, de Morton and Kent2013). Occurrence of health problems (e.g., cardiovascular, neurologic, respiratory, oncologic, mental, and musculoskeletal health disorders) and use of medication are assessed using self-reported questions.
Assessment of Low Back Pain
Twins’ experience of low back pain is assessed based on a recent consensus on the standardization of low back pain definitions for observational studies (Dionne et al., Reference Dionne, Dunn, Croft, Nachemson, Buchbinder, Walker and Von Korff2008). The self-report of low back pain is the primary outcome for this study and is investigated by asking participants if they have experienced low back pain. Twins who state they have experienced low back pain also provide the duration of the episode, number of episodes in their lifetime, and previous treatments. If participants report low back pain at baseline, their low back pain related disability and level of symptoms are assessed using the Roland Morris Disability Questionnaire (RMDQ; Costa et al., Reference Costa, Maher, Latimer, Ferreira, Pozzi and Ribeiro2007) and the Visual Analogue Scale (VAS; Scrimshaw & Maher, Reference Scrimshaw and Maher2001), respectively.
Twins are followed for 1 year with information on experience of low back pain and its associated levels of symptoms collected 3, 6, 9, and 12 months after baseline. At baseline, participants are presented with a 12-month calendar and they are asked to report days with low back pain and its associated level of symptoms using the VAS (Scrimshaw & Maher, Reference Scrimshaw and Maher2001) to facilitate recall of low back pain. Follow-ups are collected by study researchers in person, over the telephone, or electronically.
Zygosity Assessment in the BTR
Twins’ zygosity is assessed by the Portuguese version of the Peas-in-a-Pod questionnaire. The three-question questionnaire was developed and validated to assess zygosity through twins’ or twins’ parents or guardians’ self-reports, obtaining around 95% accuracy (Ooki & Asaka, Reference Ooki and Asaka2004). It has been used previously in other studies and is currently used by the Australian Twin Registry (Ooki & Asaka, Reference Ooki and Asaka2004; Rietveld et al., Reference Rietveld, van Der Valk, Bongers, Stroet, Slagboom and Boomsma2000). For adults, both twins have to complete the questionnaire, and their scores are added together to have a final score ranging from 6 to 20 with a score from 6 to 13 indicating monozygosity.
Access to the BTR
Twins are coded and their protected data are stored at the BTR database. The BTR research team and collaborators may access stored data to investigate the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The Brazilian scientific community and international researchers may access stored data using a standardized form or propose research projects to collect further information from twins in the BTR. In this case, research projects have to be approved by the BTR research team and the ethics committee of the host institution.
Future Development and Plans
The BTR is in its development stage with a promising future. The BTR has organized the first national twin festival (The first Brazilian Twins’ Festival at UFMG, Minas Gerais, in 2016) and has supported other festivals of twins in Brazil (e.g., the first Twins’ Festival at Rio Grande do Norte). Approximately 200 twins attended these festivals. As a result of our campaigns and collaborations, the BTR has identified thousands of twins who are being currently contacted to be registered. The BTR research team is acting in collaboration with twin research groups in São Paulo (São Paulo University), Rio Grande do Norte (Federal University of Rio Grande do Norte), and Santa Catarina (Federal University of Santa Catarina). Through this process and the quality of the data being collected, we expect to significantly contribute to improving the health of all Brazilians and establish a rich platform for Brazilian and international researchers.
Acknowledgments
We thank the twins who have agreed to become members of the BTR, the Australian Twin Registry, the Murcia Twin Registry, and the International Network of Twin Registries for all support. The Brazilian Twin Registry is funded by the National Council of Research (CNPq 400457/2014-8) and CAPES foundation in Brazil (CAPES BJT70_2013-400543/2013-3). None of the authors have any conflicts of interest to report.
