World of Genomics: Estonia

‘World of Genomics: Estonia’ – Original article written by Shannon Gunn, 2021. Updated by Lyndsey Fletcher, July 2023.

For the latest World of Genomics, we head over to Estonia – famous for its dense woodlands, charming historic sites in the old town of Tallinn and for having over 2,000 islands. Estonia has made great progress in the field of genetics, and also has an important indigenous heritage that has been vital in expanding its genomics reach.

The population of Estonia

Estonia is a country in Northern Europe that is bordered by Sweden, Latvia and Russia. It also has coastlines along the Gulf of Finland, the Baltic Sea and Lake Peipus.

The region of Estonia has been inhabited since at least 9,000 BC. Ancient Estonians lived on the shores of the Baltic Sea for thousands of years, making them one of the longest-settled peoples on the European continent. Estonia remained independent until the 1200s, after which it was conquered by many different empires, including Denmark, Germany, Sweden and Russia. In more recent times, Estonia was part of the Soviet Union. When the Soviet Union collapsed in 1991, Estonia finally gained its independence.

Studying the Estonian population not only provides insights into the genetic history of nation, but can also help trace recent demographic history in surrounding populations, such as Finland. Estonia has consistently ranked highly in international rankings for quality of life, education, digitalisation of public services and the prevalence of technology companies.

Geographic and demographic information

Summary statistics:

• Land area: 45,339 km²
• Gross domestic product (GDP):
  • Total: $41.55 billion (2023 estimate)
  • Per capita: $31,207 (2023 estimate)

Population statistics:

• Population size: 1,331,824 (2021)
• Birth rate: 10 per 1,000 (2021)
• Death rate: 14 per 1,000 (2021)
• Infant mortality rate: 2 per 1,000 (2021)
• Average life expectancy: 77 (2021)
  • Male: 72 (2021)
  • Female: 81 (2021)
• Ethnicity: 67.8% Estonian, 22% Russian, 10.2% other (including Ukrainians, Belarusians, Finns and Latvians).

Healthcare system

Roughly fifteen years after regaining independence, Estonia underwent radical economic reforms and widespread privatisation. The Estonian health insurance system is a solidarity-based social insurance system. It provides healthcare to around 94% of the population, and is primarily funded by mandatory contributions made through a payroll tax. It accounts for almost two-thirds of all healthcare expenditure in the country. The Estonian Health Insurance Fund (EHIF) is an independent body that remains the core purchaser of medical care and operates the national, mandatory health insurance scheme.

Estonia is a pioneer in the use of electronic health records (EHRs). It was the first country in the world that implemented a nationwide EHR system – called the Estonian Nationwide Health Information System (EHIS) – registering virtually all residents’ medical history from birth to death. It was launched in 2008. More than 99% of the data generated by hospitals and doctors is digitised. Citizens can access this information via a secure online portal and can also choose who gets to look at their records. The extensive use of digital health records served Estonia well during the COVID-19 pandemic, allowing for better test and trace practices.

According to the World Health Organisation (WHO), Estonia falls short in many aspects of their healthcare system compared to other European Union (EU) countries. Estonia spends nearly half as much on healthcare per capita compared to the average in other EU countries. It also has a 13% rate of unmet medical needs (availability and adequacy of treatments, pharmaceuticals or otherwise) compared to the European average which is under 3%. Additionally, Estonia’s life expectancy is also 2.5 years less than the European average. However, life expectancy in Estonia has increased more than in any other EU nation since 2000, rising by 7.5 years. And despite its shortfalls, the Estonian healthcare system has a high number of medical professionals and sufficient hospital facilities for the whole population.

A key challenge is the lack of adequate healthcare funding in Estonia. The country also has one of the highest rates of individuals without long-term health insurance coverage in the EU. Most importantly, Estonia’s healthcare system impacts the disadvantaged disproportionately, for example, because of the burden of out-of-pocket payments.

Health priorities

Around half of deaths in Estonia are caused by diseases of the circulatory system. Cardiovascular diseases kill more than 60% of women and 50% of men. This is followed by cancer, with lung cancer being the most deadly.

Although the reported rate of new HIV cases is declining, it is still three times higher than the EU average. In addition, the prevalence of multidrug-resistant tuberculosis is of concern, at 25% of all cases. To combat these epidemics, HIV and tuberculosis treatments are available even to uninsured individuals.

Only half of Estonians report being in good health, which is much lower than is typical in the EU. This is also much more prevalent in low-income groups, where just 34% of people assess their health as good, compared to 75% of people in the highest income quintile. This is the largest gap of any EU country.

Nearly half of all deaths in Estonia result from behavioural risks, above the EU average of 39%. This includes alcohol consumption, smoking, diet and low physical activity. For example, nearly one in five Estonian adults are now obese and one fifth of the adult population smoke daily. However, whilst obesity rates are rising, smoking and excessive alcohol consumption are becoming less common.

Estonia has implemented a National Health Plan from 2020 to 2030. The overall goal of the plan is to improve life expectancy and quality of life. In 2019, the Estonian Government also approved a bill to increase healthcare spending by €180 million on top of the normal funding. The Government hope that this additional money will improve the accessibility of healthcare services and the quality of care.

Genomic medicine capabilities

While Estonia is still in the early stages of implementing genomics and biotechnology into healthcare, it’s rapidly developing its capabilities. Genomic studies were launched in the early 1960s by a few scientists. The discipline took off in the 1970s when the first-generation of molecular biologists were educated in the University of Tartu, including Andres Metspalu, Richard Villems and Mart Saarma. Since then, the discipline has flourished, with a rise in students enrolling in genetic courses.

In December 2000, the Estonian Parliament passed a unique piece of legislation – the Human Genes Research Act. The Act regulates the establishment and maintenance of a Gene Bank to organise genetic research. It ensures voluntary and confidential gene donation and protects against discrimination and the misuse of genetic data. This Act subsequently supported the development of the Estonian Biobank, one of the largest population-based biobanks in Europe.

Clinical genetics in Estonia is largely centralised. For example, there are two clinical genetic departments in Tallinn and Tartu that provide access to advanced genetic counselling and cascade screening. Similarly, genetic testing in Estonia is mostly provided by Tartu University Hospital, although it can also be performed by private laboratories. Clinical genetic services are fully reimbursed by the EHIF.

Newborn and prenatal screening are also free of charge. Neonatal screening covers neonatal hypothyreosis and 20 treatable metabolic disorders. Breast and ovarian cancer screening is also centrally funded. Starting in 2021, public cancer screening programs became freely available for all Estonian residents, independent of their health insurance status.

Estonia is making strides in implementing precision medicine into the healthcare system. In 2018, Illumina offered free genetic testing to over 100,000 Estonians as part of the National Personalized Medicine programme, which aims to create tailored approaches to health over a five-year period.

Notable projects

• The Estonian Genome Project: Established in 2000, the Estonian Genome Project is a population-based biological database and biobank to improve public health in Estonian. It contains health records and biological specimens from a large percentage of the Estonian population.
• Estonian Biobank: The Estonian Genome Project Foundation initiated the Estonian Biobank Project in 1999. The objective was to investigate the genetic, environmental and behavioural background of common diseases and traits by creating a biobank with biological samples and health records. Its cohort size is close to 200,000 participants (≥ 18 years of age). All participants in the Estonian Biobank have been genotyped, and a considerable number have been sequenced (5,000 exomes and whole genomes).
• eQTL Catalogue: The eQTL Catalogue is a new resource developed by scientists at the University of Tartu and European Bioinformatics Institute in the UK. It provides access to standardised quantitative trait loci (QTLs) from more than two dozen public studies in human subjects.
• Precision Medicine Program: Estonia implemented digital health literacy education in 2013 for healthcare professionals and patients.
• National Personalised Medicine Programme: In 2016, Estonia launched this programme, which lays out a framework to implement personalised medicine. As part of this programme, in 2018 Estonia offered thousands of residents free genetic testing, making it the first nation to offer its citizens state-sponsored genetic information and advice.

Notable organisations and companies

• Estonian Society of Human Genetics (ESTSHG): Founded in 1999, ESTSHG is a non-profit organisation that promotes research and communication between scientists in the field of human and medical genetics.
• Institute of Genomics: Situated in the University of Tartu, the Institute of Genomics conducts transdisciplinary basic and applied research and teaching based on omics research and methods. It is also the operator and developer of the Estonian gene bank and offers genomics laboratory services.
• Nordic Society for Precision Medicine: Encompassing Estonia, Denmark, Iceland, Norway, Finland and Sweden, the Nordic Society for Precision Medicine aims to understand the genetic makeup of the Nordic region. By facilitating research and implementing appropriate legislation, the Society aim to create personalised medicine approaches for the Nordic population.

Notable individuals

• Toomas Kivisild (1969-): Kivisild is an Estoninan population geneticist whose research focusses on questions relating to global genetic population structures with evolutionary processes, such as selection, drift migration and admixture.
• Andres Metspalu (1951-): Metspalu is a geneticist and the President of the Estonian Human Genetics Society. His fields of research include genetic engineering, gene technology and molecular diagnostics, as well as the genetics of complex diseases.
• Riin Tamm (1981-): Tamm is an Estonian geneticist and a science populariser. She is a board member of the Estonian Society of Human Genetics and the Estonian Association of Gerontology and Geriatrics.
• Richard Villems (1944-): Villems is an Estonian geneticist and the ex-President of the Estoninan Academy of Sciences. He is currently a Professor of Population Genetics at the University of Tartu.
• Tõnu Esko: Esko is a Vice Director of Development and Head of the Estonian Biobank Innovation Center at the Institute of Genomics, University of Tartu. He is also Professor of Human Genomics.
• Mart Saarma (1949-): Saarma is an Estonian molecular biologist and member of the Estonian Academy of Sciences. His main research is dedicated to virus resistance, the development of the nervous system and neurodegenerative diseases.

Future Genomics Landscape

The research environment in Estonian is improving annually, both in terms of funding and scientific level. The Estonian Government has been investing in the realisation of personalised medicine at the national level, and its Biobank will continue to provide valuable data that will improve research and healthcare within Estonian and beyond.

With the passing of the Human Genes Research Act, Estonia has established a favourable environment to implement personalised medicine. Additionally, Estonia’s investment in a national IT infrastructure has digitised many aspects of daily life. This digitisation has enabled linking of Estonian health registries and hospitals and has also facilitated the sharing of medical information for patients. The nation is also continuously increasing its precision medicine capabilities, and just this year announced that £30 million of EU funding would go towards building a Personalised Medicine Centre of Excellence.

As Estonia continues to push forward in the field of personalised medicine, efforts will need to be made in education and demonstrating the public benefits of genomic screening. These efforts must be executed in a manner that is both ethical and ensures the security and privacy of data. Other challenges will involve developing professional genetic knowledge and skills and ensuring that the workforce is prepared. Finally, Estonia faces challenges financing and management, particularly in the R&D sector. As research across universities and institutes grows, and networking among researchers develops, Estonia will improve its international competitiveness and enable them to be a key player in the genomics field.

References

• Vrijenhoek T, Tonisson N, Kääriäinen H, Leitsalu L, Rigter T. Clinical genetics in transition—a comparison of genetic services in Estonia, Finland, and the Netherlands. Journal of Community Genetics. 2021 Apr;12(2):277-90.
• Prins BP, Leitsalu L, Pärna K, Fischer K, Metspalu A, Haller T, Snieder H. Advances in Genomic Discovery and Implications for Personalized Prevention and Medicine: Estonia as Example. Journal of personalized medicine. 2021 May;11(5):358.