The GoGreece initiative
Background
In the post-genomic era, genomic medicine interventions, as a key component of personalized medicine and tailored-made health care, are greatly anticipated following recent scientific and technological advances. Currently, a multidisciplinary agenda that involves government officials, funding agencies, industry leadership, health care providers, biomedicine researchers and the general public becomes of outmost importance to “translate” human discoveries into the clinic. There is the perception that the benefits of genomics are attainable both inside and outside the industrialized world. Indeed, large-scale sequencing efforts that explore human genomic variation have been initiated in several countries across the globe, following the paradigm of the countries that have already embarked on major genomics initiatives, such as the United States and the United Kingdom.
Rationale
The "GoGreece" initiative is a long-term National Genomics project focused on the implementation of Genomic Medicine in Greece. In particular, the long-term aims and goals of the “Genome of Greece (GoGreece)” initiative is to:
a. Determine the allelic architecture of the Hellenic population, especially focusing on rare, pathogenic or not, variants that are characteristic for the Hellenic population,
b. Characterize the unique allelic spectrum of isolate populations in Greece, such as the islands, mountainous regions, as well as population groups such as Greek Roma and Pomaks,
c. Establish the pathogenic variant spectrum of common and rare genetic diseases in the Greek population,
d. Develop and maintain a comprehensive knowledgebase documenting the extant genetic heterogeneity in the Greek population, as far as pathogenic variants and polymorphic alleles are concerned,
e. Address important ethical, legal and societal issues pertaining to the implementation of Genomic Medicine interventions in Greece,
f. Enhance the genomics education of healthcare professionals and biomedical scientists in Greece, and
g. Raise genomics awareness of the general public
Our approach
A. Next-generation sequencing
The core element of the “GoGreece” initiative is the sequence analysis of a large number of individuals from the Hellenic population using next-generation sequencing approaches, specifically by targeted resequencing and/or whole exome and/or whole genome sequencing. In particular, we aim to analyze:
- A large number (>1000) of healthy donors of Hellenic origin, to determine the allelic architecture of the population, especially the pharmacogenomic variants for population pharmacogenomics,
- Cohorts of patients, suffering from rare multifactorial genetic diseases, such as amyotrophic lateral sclerosis, celiac disease, multiple sclerosis, etc., to identify the underlying genetic etiology,
- Cohorts of patients, suffering from monogenic diseases, such as cystic fibrosis and β- thalassemia to identify genetic modifiers of the final clinical phenotype.
B. Informatics tools and knowledgebase
At the same time, we have developed and currently populating the Hellenic National genetic database to store the generated genomic data, in a de-identified manner to ensure patient and healthy donor data anonymity. This database is accompanied by a set of informatics tools that calculate the allelic frequencies in a dynamic manner and present them in an aggregated form to depict the cumulative allelic frequencies for the Hellenic population.
Data deposition follows the microattribution concept to incentivize genomic data submission.
C. Public engagement
Implementation of genomic medicine dictates the fine mapping of the stakeholders’ environment. We have used structured questionnaires, face-to-face interviews and surveys to assess the opinion and standpoint of the various stakeholders in Greece, such as the Ministry of Health, National Medicines Organization, payers and insurance companies, biotechnologies and pharmaceutical companies, academic institutions and research institutes, clinicians (geneticists and other specialties), biomedical scientists, professional organizations, media and the press and religious organizations. Lastly, we have documented the existing genetic laboratories in Greece and, currently, this information is being compiled into a data repository to be directly assessible from the general public and clinicians.
D. Genomics education and awareness
The “GoGreece” initiative is committed to raise genomics education and awareness of the Hellenic population, both the general public and healthcare professionals and biomedical scientists. Using questionnaires and surveys, we have first assessed the level of genomics awareness and genetic education of the general public and of healthcare professionals, respectively. Also, we have developed e-learning courses in the field of genomic medicine ensuring continuous medical education of interested healthcare professionals and biomedical scientists, while we have also established a mobile molecular biology laboratory (2MoBiL) aiming to familiarize primary and high school students and their teachers with the basic notions of genomic medicine. Lastly, since 2019, we are publishing a new Greek scientific journal [Εξατομικευμένη Ιατρική (Personalized Medicine), ISSN 2653-9470; www.permed.gr], the first in the fields of Human Genomics and Personalized Medicine, while as of 2019, we launched a same-themed annual conference series, aiming to become a focal point and the main forum for experimental and implementation work pertaining to Personalized Medicine in Greece.
Preliminary findings
The “GoGreece” initiative has delivered, so far, the following preliminary findings:
a. We have identified a novel genomic locus associated with sporadic ALS in Greek ALS patients, using whole genome sequencing, and the first evidence implicating an obesity- related gene in ALS pathogenicity (Mitropoulos et al., 2017),
b. We have identified a novel genomic locus associated with pediatric celiac disease in Greek celiac disease patients, using a whole genome sequencing approach (Balasopoulou et al., 2016),
c. We have demonstrated the utility of whole genome sequencing analysis in pharmacogenomics, by using a Greek family as a paradigm (Mizzi et al., 2014)
d. By using comparative genomic analysis between whole genome sequences from individuals from Caucasian and Greek origin, we have identified >50 genomic variants that are characteristic form the Hellenic population (unpublished),
e. We have developed a dedicated tool to store genomic sequences, derived from targeted resequencing, whole exome and whole genome sequencing, using the microattribution approach (in preparation),
f. We have performed a comprehensive analysis to assess the level of genomics awareness of the general public (Mai et al., 2011) g. We have assessed the level of genomics education of healthcare professionals and biomedical scientists (Pavlidis et al., 2012; Mai et al., 2014)
h. We have performed a comprehensive analysis of the services provided by private molecular genetic laboratories in Greece (Sagia et al., 2011; Kechagia et al., 2014)
i. We have explored and recorded the views and opinions of various stakeholders involved in personalized medicine and pharmacogenomics in Greece (Mitropoulou et al., 2014)
j. We have evaluated the academic educational environment in Greece as far as pharmacogenomics is concerned, both at the under- and post-graduate level (Pisanu et al., 2014)
Expected Impact
The “GoGreece” initiative has already demosntrated excellence leading to some tangible deliverables, focusing on: (a) discovery of novel candidate loci for multifactorial and modifier genes in monogenic diseases, (b) public health genomics aspects catalyzing the implementation of genomic medicine in Greece.
This project aims to recruit a very large number of Greek individuals (>100,000) in an at least 10-year horizon, both healthy donors, in order to determine the allelic architecture of the Hellenic population and patients suffering from monogenic and multifactorial diseases, in order to delineate the genetic etiology of the underlying clinical phenotype.
This project is expected to have a big impact in the elucidation of the genetic basis of inherited diseases in Greece, especially in Isolated populations and to catalyze the implementation of personalized medicine in the Greek healthcare system.
References
1. Mitropoulos K, Merkouri Papadima E, Xiromerisiou G, Balasopoulou A, Charalampidou K, Galani V, Zafeiri KV, Dardiotis E, Ralli S, Deretzi G, John A, Kydonopoulou K, Papadopoulou E, di Pardo A, Akcimen F, Loizedda A, Dobričić V, Novaković I, Kostić VS, Mizzi C, Peters BA, Basak N, Orrù S, Kiskinis E, Cooper DN, Gerou S, Drmanac R, Bartsakoulia M, Tsermpini EE, Hadjigeorgiou GM, Ali BR, Katsila T, Patrinos GP. (2017). Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients. Hum Genomics. 11(1): 30.
2. Balasopoulou B, Stanković B, Panagiotara A, Nikčevic G, Peters BA, John A, Mendrinou E, Stratopoulos A, Legaki AI, Stathakopoulou V, Tsolia A, Govaris N, Govari S, Zagoriti Z, Poulas K, Kanariou M, Constantinidou N, Krini M, Spanou K, Ali BR, Borg J, Drmanac R, Chrousos G, Pavlovic S, Roma E, Zukic B, Patrinos GP, Katsila T. (2016). Novel genetic risk variants for pediatric celiac disease Hum Genomics 10(1): 34.
3. Vozikis A, Stavropoulou L, Patrinos GP. (2015). Community Pharmacists’ strategies in Greece: An assessment of the policy environment and the mapping of key players. Health, 7: 1560-1577.
4. Mitropoulou C, Mai Y, van Schaik RH, Vozikis A, Patrinos GP. (2014). Documentation and analysis of the policy environment and key stakeholders in pharmacogenomics and genomic medicine in Greece. Public Health Genomics 17(5-6): 280-286.
5. Mizzi C, Mitropoulou C, Mitropoulos K, Peters B, Agarwal MR, van Schaik RH, Drmanac R, Borg J, Patrinos GP. (2014). Personalized pharmacogenomics profiling using whole genome sequencing. Pharmacogenomics, 15(9): 1223-1234.
6. Kechagia S, Yuan M, Vidalis T, Patrinos GP, Vayena E. (2014). Personal Genomics in Greece: An Overview of Available Direct-to-Consumer Genomic Services and the Relevant Legal Framework. Public Health Genomics 17(5-6): 299-305.
7. Pisanu C, Tsermpini EE, Mavroidi E, Katsila T, Patrinos GP, Squassina A. (2014). Assessment of the Pharmacogenomics Educational Environment in Southeast Europe. Public Health Genomics 17(5-6): 272-279.
8. Mai Y, Mitropoulou C, Papadopoulou XE, Vozikis A, Cooper DN, van Schaik RH, Patrinos GP. (2014). Critical appraisal of the views of healthcare professionals with respect to pharmacogenomics and personalized medicine in Greece. Per Med, 11(1): 15-26.
9. Pavlidis C, Karamitri A, Barakou E, Cooper DN, Poulas K, Topouzis S, Patrinos GP. (2012). Analysis and critical assessment of the views of the general public and healthcare professionals on nutrigenomics in Greece. Per Med, 9(2): 201-210.
10. Mai Y, Koromila T, Sagia A, Cooper DN, Vlachopoulos G, Lagoumintzis G, Kollia P, Poulas K, Stathakopoulos V, Patrinos GP. (2011). A critical view of the general public’s awareness and physicians’ opinion of the trends and potential pitfalls of genetic testing in Greece. Per Med, 8(5): 551-561.
11. Sagia A, Cooper DN, Poulas K, Stathakopoulos V, Patrinos GP. (2011). A critical appraisal of the private genetic and pharmacogenomic testing environment in Greece. Per Med, 8(4): 413-420.