Genomic Medicine Alliance

The recent advances in the genomic technology and deciphering of the human genome sequence have opened new paths in modern medicine but also posed ethical challenges and dilemmas. Coverage and reimbursement of genetic tests, genetic testing provided directly to the public (also known as DTC genetic testing), intellectual property of genomic information, genetic discrimination, informed consent, genome statutes and legislation, as well as personal genome access are some of the new challenges that genomic evolution have created.

Genethics aims to address these challenges and this working group is currently performing surveys in various target groups in several countries to address some of the above issues to allow a better assessment of the ethical legal, and social framework of genetic testing in several countries.

The Genomics and Pharmacogenomics Working Group aims to undertake and coordinate research projects that will facilitate the integration of genomics applications and pharmacogenomics into healthcare. This Working Group activities span into three different fields:

1. Pharmacogenomics

2. Rare Diseases,

3. Cancer Genomics.

1. Pharmacogenomics

This Working Group has undertaken a project to provide proof-of-principle of the use of whole-genome sequencing for pharmacogenomic testing, by resequencing with high coverage, of almost 500 human genomes, mostly from Caucasian populations. This project indicated that not only a vast number of novel potentially functional variants in a total of 231 pharmacogenes was identified but also demonstrated the value of whole-genome sequencing for pharmacogenomic testing by capturing over 18,000 variants per individual in these pharmacogenes. These efforts are expected to yield important results with very positive implications for public health as it can improve the quality of life, as well as help towards reducing healthcare costs.

Also, this Working Group has completed the first Pan-European study to determine the prevalence of PGx biomarkers in several European populations. Results of this study has shown that there is a significant inter-population variability, as far as pharmacogenomic biomarker allele frequency is concerned, which has a direct impact on the rationalization of drug use at a population level. This project is currently being replicated in Southeast Asia, in close cooperation with the SEAPharm Consortium and the Global Genomic Medicine Collaborative.

References:

Mizzi C, et al. (2014). Personalized pharmacogenomics profiling using whole genome sequencing. Pharmacogenomics, 15(9): 1223-1234. 

Mizzi C, et al. (2016). A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics. PLoS One. 11(9): e0162866. 

2. Rare Diseases

Rare diseases (RD) has been estimated to be more than 7.000; whilst individual conditions can be very infrequent. RD overall affect millions of citizens at global level and are considered a significant issue. RD are not a neglected topic anymore. In the last decade, several targeted actions at international, European and national level, have tackled both public health and research aspects.

However, a lot remain to be performed mainly at diagnostic and treatment level. In particular, about 30% of patients are still undiagnosed; moreover, only symptomatic therapy is still available for the majority of persons with RD. 

Work in this Working Group is conducted in close collaboration with other scientific bodies (IRDiRC, ICORD) and institutions (RD at NCATS, UDP at NIH, ISS) active in the field of Rare Diseases and focuses on:

a. Rare undiagnosed diseases

b. Rare phenotypes within rare conditions

c. Rare pharmacogenomic-related adverse drug reactions

Members of this Working Group aim to steer the development of research on RD in developing countries, by transferring and sharing scientific expertise, models and best practices as well as by seeking contacts with Universities, scientific associations, institutions and patient organizations.

Selected links:

http://www.irdirc.org 

http://icord.se 

http://www.iss.it/cnmr 

http://www.ncats.nih.gov 

http://rarediseases.info.nih.gov 

http://ec.europa.eu/health/rare_diseases/portal/index_en.htm 

http://www.rarediseases.info.nih.gov/research/pages/27/undiagnosed-diseases-program

3. Cancer Genomics

Over the past decade due to the deep-sequencing technologies, we have studied the characterization of nucleic acid alterations in a wide range of cancers generating a large body of information on how cancer develops and evolves. Likewise, genomic testing has moved from a limited research activity to specialized institutes, to a clinical test available in dozens of academic and commercial laboratories.

Members of this Working Group have undertaken a study to identify cancer predisposition (germline) variants in apparently healthy individuals with no cancer history in the family using a next-generation sequencing strategy.

Such an approach aimed to intentify genomic, particularly novel variants that might predispose to various types of cancer so that such information could help in the assessment of personalized cancer-susceptibility risk from genome sequence data.

References:

Karageorgos Ι, et al. (2015). Identification of cancer predisposition variants using a next generation sequencing-based family genomics approach. Hum Genomics. 9: 12.

The Public Health Genomics Working Group has been engaged in national and transnational studies to improve our understanding of the level of healthcare professionals and the public awareness of genetics and the various ethical, legal and societal issues that relate to the implementation of genomics into healthcare. In particular, activities of this Working Group focus on the following fields:

1. Applied Genomics and Public Health,

2. Ethics in Genomics 

1. Applied Genomics and Public Health

Members of this Working Group have performed surveys aiming to highlight both the extend of genetics education of healthcare professionals and genetic awareness and literacy of the general public.

These studies provide the basis for a critical assessment of the views of the general public and healthcare professionals on genomics and genetic testing services in several countries worldwide, while these surveys could be readily replicated in other countries with the ultimate aim of improving the public understanding of genetics and genetic testing, and facilitating the incorporation of genomic medicine into everyday clinical practice.

Furthermore, a detailed stakeholder analysis was undertaken aiming to the comprehension of attitudes and the mapping of the genomic medicine policy environment. The foundings contributed to the selection and implementation of policy measures by adopting the genomics into conventional medical interventions.

Similar studies are currently being replicated in Southeastern Asian and the Middle Eastern countries, under the umbrella of Genomic Medicine Alliance and are partly supported by the Golden Helix Foundation confirming initial findings and highlighting the need to harmonize genomics education aiming to the raise of genomics awareness to the general public.

Lastly, members of this Working Party have proposed an approach for expediting the integration of Genomic Medicine in resource-limited environments, based on the “Fast-Second winner” strategy.

References:

Pisanu C, et al. (2014). Assessment of the Pharmacogenomics Educational Environment in Southeast Europe. Public Health Genomics 17(5-6): 272-279.     

Mitropoulou C, et al. (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.   

Mitropoulos K, et al. (2015). Success stories in genomic medicine from resource-limited countries. Hum Genomics 9: 11.

Mitropoulos K, et al. (2017). Genomic Medicine Without Borders: Which Strategies Should Developing Countries Employ to Invest in Precision Medicine? A New "Fast-Second Winner" Strategy. OMICS 21(11): 647-657.  

Balasopoulou A, et al. (2017). Advancing Global Precision Medicine: An Overview of Genomic Testing and Counseling Services in Malaysia. OMICS 21(12): 733-740. 

2. Ethics in Genomics

The recent advances in the genomic technology and deciphering of the human genome sequence have opened new paths in modern medicine but also posed ethical challenges and dilemmas.

Several ethical issues confront those who are committed to the practice of Genomic Medicine, including the regulation of genetic testing, the governance of genetic research and genomic data sharing in an ethical and publicly accountable way.

This Working Group explores the landscape of direct-to-consumer, beyond the clinic and over-the-counter genetic tests in various countries worldwide, taking always into serious consideration the interethnic and cultural differences.

At the moment, regulation of safeguarding the general public by ensuring them that they become better informed from this type of testing, cost coverage and reimbursement of genetic tests, are lacking in many European countries as well as at a central level.

This Working Group also works closely with the National Genetic Societies and National Ethics Committees to establish guidelines covering ethical, legal and social issues to genetic testing.

References:

Patrinos GP, et al. (2013). Genetic tests obtainable through pharmacies: The good the bad and the ugly. Hum Genomics 7:17.   

Kechagia S, et al. (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. 

Balasopoulou A, et al. (2017). Advancing Global Precision Medicine: An Overview of Genomic Testing and Counseling Services in Malaysia. OMICS 21(12): 733-740. 

Members of the Genome Informatics Working Group have recognized the need to provide a comprehensive resource for pharmacogenomic biomarkers information for those drugs that are approved by regulatory authorities.

The process they have followed in order to gather the specific information was to extract from the published literature all pharmacogenomic biomarkers that relate to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved drugs with pharmacogenomic information in their label and make them available in a database that triangulates between drugs, genes and pharmacogenomics biomarkers.

This Database was developed jointly with the Global Genomic Medicine Collaborative Pharmacogenomics Working Group and it has been named DruGeVar.

All DruGeVar database records involve correlations between 91 drugs, 13 genomic loci and 98 genomic variants which has previously implicated in variable drug responses both in terms of efficacy and toxicity. The registered records depict drug/gene combinations have been approved by any or both of the two regulatory agencies and are available to the public for data querying.

Recently, the DruGeVar database was included as a plug-in module for the pharmacogenomic biomarkers module of FINDbase database, while new data visualization functionalities were added to facilitate data querying output. Overall, the DruGeVar database is expected to contribute towards bridging the gap between pharmacogenomics research findings and clinical practice.

Finally, the FINDbase worldwide database for clinically relevant genomic variation allele frequencies continues to be updated with new functionalities and content, thanks to the joint efforts of the Genome Informatics Working Group.

References

Dalabira E, et al. (2014). An online resource triangulating drugs with genes and biomarkers for clinical pharmacogenomics. Public Health Genomics 17(5-6): 265-271. 

Viennas E, et al. (2017). Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies. Nucleic Acids Res 45(D1): D846-D853. 

Sarris K, et al. (2017). Application of the DruGeVar Database in Cancer Genomics and Pharmacogenomics. Public Health Genomics 20(2): 142-147.