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The Hungarian Twin Registry

Published online by Cambridge University Press:  19 October 2012

Levente Littvay ,
Julia Métneki ,
Ádám D. Tárnoki  and
Dávid L. Tárnoki
Levente Littvay*
Affiliation:
Central European University, Budapest, Hungary
Julia Métneki
Affiliation:
National Institute for Health Development, Budapest, Hungary
Ádám D. Tárnoki
Affiliation:
Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary
Dávid L. Tárnoki
Affiliation:
Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary
*
address for correspondence: Levente Littvay, Central European University, Nádor u. 9., Budapest 1051, Hungary. E-mail: littvayl@ceu-budapest.edu

Abstract

The first Hungarian Twin Registry was established in Budapest in 1970 through the mandatory reporting of multiple-births. In the 1980s a second, volunteer adult registry was also founded. Unfortunately, both registries ceased to exist in the 1990s. Efforts started in 2006 to revive a Hungarian twin registry. The team spearheading this effort reports here on this progress. Currently, the voluntary Hungarian Twin Registry consists of 310 adult twin pairs and multiplets. Current research focuses on cardiovascular and respiratory health and yielded multiple awards and publications. Efforts are on the way to expand into social, psychological, and obesity studies.

Keywords

Central and Eastern Europepost-communist erainternational twin studyarterial stiffnesshypertensionlung function

In 2006, two medical students — Adam and David Tarnoki (identical twins themselves) — and Levente Littvay began an effort to revive the Hungarian Twin Registry. This effort benefited greatly from the help of Julia Métneki (a twin herself), the person responsible for most of Hungarian twin studies and the management of two twin registries from the 1970s to the 1990s. Levente Littvay is especially grateful to Nicholas Martin for his encouragement to get in touch with Julia Métneki and continue the work she started in the 1970s. This team now reports the progress of this project, the rebirth of a volunteer twin registry in Hungary and future plans.

History

Twin studies in Hungary date back to 1970s, on the basis of three different databases, all of them through the efforts of Andrew Czeizel. The Budapest Twin Registry (BTR) was launched in 1970 by the Department of Human Genetics and Teratology, National Institute of Hygiene. The notification of all multiple births (including stillbirths) was carried out by physicians of obstetrical institutions in the capital. The registry's purpose revolved first around ensuring twins’ developmental health in the perinatal and postnatal periods. Placentas were collected and analyzed in the Heim Pál Children's Hospital. In addition, twin zygosity was determined in all dichorionic like-sex twins by determining their blood and serum protein groups. Twins’ health was assessed by pediatricians at 6 months and at 1, 3, 6, and 10 years of age (Czeizel et al., Reference Czeizel, Pazonyi, Métneki and Tomka1979). As a byproduct, the BTR offered a unique opportunity for scientific research. For example, a connection between contraceptive pills containing high dose hormones used in the periconceptional period and frequency of dizygotic twin births was demonstrated (Métneki & Czeizel, Reference Métneki and Czeizel1980). Other research associated with the BTR focused not only on genetic questions but risk factors in twin births. One such study assessed retinopathia prematorum, which is associated with premature births and is a risk factor of multiple births (Métneki et al., Reference Métneki, Czeizel and Vitéz1991). Also, the duration of gestation and the intrauterine growth of multiple fetuses was compared to singletons (Török et al., Reference Török, Métneki, Intődi, Csákány, Doszpod and Gáti1985, Reference Török, Mészáros, Métneki, Dobos, Hajdu, Doszpod and Gáti1988). Additional research evaluated the demographic and epidemiological characteristics of multiple births (Métneki, Reference Métneki1996; Métneki & Czeizel, Reference Métneki and Czeizel1983, Reference Métneki, Czeizel, Véghelyi and Kerpel-Fronius1986).

Unfortunately, due to a lack of funding, the twins’ health program was dissolved in the 1980s, and in the 1990s institutional and administrational changes led to the complete discontinuation of the registry. In the early 1980s, after a successful study of lactose intolerance on the population and the need for an adult twin sample in order to estimate the hereditary model of this phenomenon, Julia Métneki and Andrew Czeizel initiated a second, volunteer adult twin registry, recruiting with newspaper ads and other media presence (Flatz et al., Reference Flatz, Czeizel, Métneki, Flatz, Kühnau and Jahn1985; Métneki, Reference Métneki1996; Métneki et al., Reference Métneki, Czeizel, Flatz and Flatz1984).

These two twin registries allowed for multiple national research projects assessing child age math aptitude, intelligence, creativity, and musical talent, augmented with neurophysiological assessments (Métneki, Reference Métneki1996). Other studies focused on psychological and sociological characteristics; one study assessed premenstrual syndrome symptoms as a mood disorder and suicide risk factors (Métneki, Reference Métneki1996), another the impact of metal load on heart rate variability (Láng et al., Reference Láng, Szilágyi, Métneki and Weisz1992).

In a collaboration with dentists, a comparative study was performed on the consumption of cariogenic food in MZ and same-sex DZ twins (Pados et al., Reference Pados, Métneki and Pál1989).

After investigating the effect of periconceptional multivitamin supplementation containing folic acid on fertility in the pregnant women taking part in the Hungarian Optimal Family Service, Andrew Czeizel and Julia Métneki first reported their ‘side-effect’, namely, the higher frequency of twin pregnancies (Czeizel et al., Reference Czeizel, Métneki and Dudás1994).

Recently, a never before published psychosexual assessment was made available to the international research community (Métneki et al., Reference Métneki, Tarnoki, Tarnoki, Littvay and Czeizel2011). Much of the results were reconstructed from notes, summary statistics, and presentation slides from the 1980s and 1990s. Attempts to revive the original data involved going through bulk paper storage without appropriate filing, often matching handwriting, for surveys where the paper clips had fallen off and the pages had become shuffled. Despite our efforts, we could not reconstruct all of the original data (due to one missing container with almost all DZ male respondents). The female sample was almost entirely reconstructed and is being processed now in the hope of future studies.

The availability of the registries also led to multiple international collaborations, including a study with the Hamburg Genetic Institute on alcohol consumption, sensitivity, and metabolism (Agarwal et al., Reference Agarwal, Goedde, Benkmann, Métneki, Agarwal, Buda, Czeizel and Goedde1997), a melanoma prevention study in collaboration of the Hamburg Dermatology Clinic looking at naevi (Roser et al., Reference Roser, Métneki, Weichenthal, Thrane and Breitbart1993; Breitbart et al., Reference Breitbart, Métneki, Weichenthal, Thräne, Béres, Rott and Breitbart1996; Weichenthal et al., Reference Weichenthal, Roser, Métneki and Breitbart1994), and the already cited study on adult lactose intolerance in collaboration with the World Health Organization and the Hannover Human Genetics Institute (Flatz et al., Reference Flatz, Czeizel, Métneki, Flatz, Kühnau and Jahn1985; Métneki et al., Reference Métneki, Czeizel, Flatz and Flatz1984).

The third database, the Hungarian Congenital Abnormality Registry (HCAR), was established in the same year as the BTR (1970) and included personal and medical data of multiple births (Czeizel, Reference Czeizel1996). This population-based registry offered also a unique opportunity to study the relation of twinning and birth defects in national (Métneki, Reference Métneki1978; Métneki & Czeizel, Reference Métneki and Czeizel1987; Métneki et al., Reference Métneki, Pazonyi and Czeizel1992, Reference Métneki, Czeizel and Evans1996) and international studies (Mastroiacovo et al., Reference Mastroiacovo, Castilla, Arpino, Botting, Cocchi, Goujard and Rosano1999). In a Hungarian study of conjoined twins, the role of genetic factors was found to be negligible as compared to the environmental (teratogenic and maternal) effect in the etiology (Métneki & Czeizel, Reference Métneki and Czeizel1989). Recently, HCAR took part in a multicenter worldwide collaborative epidemiological study of the International Clearinghouse for Birth Defects Surveillance and Research, including 21 Clearinghouse Surveillance Programs related to conjoined twins (Mutchinick et al., Reference Mutchinick, Luna-Muñoz, Amar, Bakker, Clementi, Cocchi and Arteaga-Vázquez2011). The recent international registry-based study in collaboration with 14 European countries 1984–2007 organized by EUROCAT outlined the long-term consequences of the increasing prevalence of multiple births observed in the last two decades (Boyle et al., in press).

Current Research

A Hungarian Twin Club was founded in the early 1980s, and since then twin meetings are common around the country. Annual meetings are held at Szigethalom (13th annual national meeting in 2012), Ágfalva (6th annual international meeting in 2012), and Kunhegyes (9th biannual meeting in 2012). The old volunteer registry and these meetings are at the foundation of the new volunteer twin registry. Additionally, we are augmenting this list with social media presence, a continuous push in the more traditional media, and via the website (http://www.ikerkutatas.club.hu). Adam and David Tarnoki (winners of the ‘Most alike male twins between 20–25 years’ award at Twinsburg in 2006) regularly appear in the media discussing twin meetings and new findings of twin studies, and regularly make public appeals for both MZ and DZ twins to join the registry.

Since the revived efforts in 2007, multiple studies have been published. A study led by Gyorgy Jermendy and János Osztovits involved 101 twin pairs and investigated the genetic effects on the risk factors of metabolic syndrome and cardiovascular autonomic function (Jermendy et al., Reference Jermendy, Littvay, Steinbach, Jermendy, Tárnoki, Tárnoki and Osztovits2011a, Reference Jermendy, Horváth, Littvay, Steinbach, Jermendy, Tárnoki and Osztovits2011b, Reference Jermendy, Horváth, Littvay, Steinbach, Jermendy, Tárnoki and Osztovits2011c; Osztovits et al., Reference Osztovits, Horvath, Littvay, Steinbach, Jermendy, Tarnoki and Jermendy2011). The article published in the Hungarian Medical Journal (Orvosi Hetilap) received the journal's prestigious Markusovszky award of excellence in 2011. Additional twin studies focused on sensitivity to weather changes (Tarnoki et al., Reference Tarnoki, Tarnoki, Metneki and Dakay2007) and venous biomechanics (Tarnoki et al., Reference Tarnoki, Molnar, Tarnoki, Kulcsar, Littvay, Garami and Nádasy2012a).

In addition to the national studies, the registry already engaged in multiple international collaborations mainly with the Italian Twin Registry (Fagnani et al., Reference Fagnani, Brescianini, Cotichini, D'Ippolito, Dukic, Giannantonio and Stazi2006). An international twin study was organized by Adam and David Tarnoki in Hungary, Italy (Rome, Padua, Perugia), and in the United States (Twinsburg) in 2009 and 2010 involving 160 Hungarian, 180 Italian, and 50 American twin pairs. Italian twins were recruited by the Italian Twin Registry. The study involved over 20 comprehensive, mainly anthropometric, cardiovascular, respiratory, and ophthalmologic measurements. The results were presented at various international meetings and one study received the European Respiratory Society's Annual Inflammatory Airway Diseases and Clinical Allergy Grant award for the third best paper in 2010. The publication of the results is still in progress (Medda et al., Reference Medda, Fagnani, Tarnoki, Tarnoki, Cotichini, Penna and Stazi2012; Rácz et al., Reference Rácz, Tóth, Székelyhídi, Tárnoki, Tárnoki, Littvay and Németh2011; Tarnoki et al., Reference Tarnoki, Tarnoki, Medda, Karlinger, Molnar, Garami and Berczi2010a, Reference Tarnoki, Tarnoki, Stazi, Medda, Cotichini, Baracchini and Horvath2010b, Reference Tarnoki, Tarnoki, Stazi, Medda, Cotichini, Baracchini and Horvath2010c, Reference Tarnoki, Tarnoki, Stazi, Medda, Cotichini, Fagnani and Garami2011a, Reference Tarnoki, Tarnoki, Karlinger, Molnar, Garami and Berczi2011b, Reference Tarnoki, Molnar, Tarnoki, Kulcsar, Littvay, Garami and Nádasy2012a, Reference Tarnoki, Tarnoki, Bata, Littvay, Osztovits, Jermendy and Berczi2012b, Reference Tarnoki, Tarnoki, Medda, Stazi, Baracchini, Meneghetti and Garami2012c, Reference Tarnoki, Tarnoki, Stazi, Medda, Cotichini, Nisticň and Schillaci2012d, Reference Tarnoki, Tarnoki, Stazi, Medda, Cotichini, Penna and Horvath2012e).

In 2012, data was collected on ideology and political participation to supplement a multi-country meta-analysis of political attitudes. We are planning additional studies on obesity-discordant MZ twins with the collaboration of Kirsi Pietiläinen (Finnish Twin Registry) (Kaprio, Reference Kaprio2006). In addition, a social, psychological, further cardiovascular, and respiratory twin studies are in progress.

Characteristics of the Registry

Currently, the registry consists of 310 adult twin pairs (or multiplets — 65% MZ, 15% DZ, 20% DZO — 6 triplets, 1 quadruplet, 70% female, mean age 44 ± 16 years). As it is common with volunteer registries, we also have a higher proportion of MZ and female twins (Lykken et al., Reference Lykken, Tellegen and De Rubeis1978). In the current database, we have data on risk factors, diseases, and surgeries in addition to contact information (including address, telephone, and email). We archived various data on past studies (e.g., blood pressure, arterial stiffness; carotid, cervical, and abdominal ultrasound; lung function; airway responsiveness; grip strength; body composition; echocardiography; venous distensibility and elasticity; several laboratory parameters; smoking, nutrition, physical, and social activity data).

Zygosity is assessed with multiple questions and latent class analysis in line with the recommendations of Heath et al. (Reference Heath, Nyholt and Neuman2003). Due to lack of funding, twins rarely receive any incentives for participation in studies. In the study led by György Jermendy they were offered travel reimbursements.

Future Directions

At this point in time, the management of the increased interest in twin studies is challenging. It is especially important that twins are not bothered too often with study requests. In the short run, we are increasing the size of the volunteer registry and continuing the work that started in 2007 with international collaborations. In the long run, we are hoping for the establishment of a population-based twin registry either through the utilization of the 1970–1980s Budapest multiple birth records cited above or using population databases available to the government which contain birth name, birthplace, birthday, and mother's maiden name. Matching on all these records could yield a list of highly probable twin individuals. Unfortunately (or fortunately), Hungary's strict privacy laws and the quickly changing legal structures (e.g., recently changed constitution, uncertainty concerning existing case law, rewriting of many laws, all done in the past few years) make both of these efforts difficult. Health records and family relation information have, in the past, been classified as especially sensitive by law and case law. Hopefully, the uncertainty associated with the legal changes will be alleviated as time passes or, if needed, new regulations will make the expansion of a population-based twin registry possible.

Footnotes

The authors contributed equally to this article and appear in alphabetical order.

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