We present, on behalf of EuroGentest and the European Society of Human Genetics, guidelines for the evaluation and validation of next-generation sequencing (NGS) applications for the diagnosis of genetic disorders. The work was performed by a group of laboratory geneticists and bioinformaticians, and discussed with clinical geneticists, industry and patients’ representatives, and other stakeholders in the field of human genetics. The statements that were written during the elaboration of the guidelines are presented here. The background document and full guidelines are available as supplementary material. They include many examples to assist the laboratories in the implementation of NGS and accreditation of this service. The work and ideas presented by others in guidelines that have emerged elsewhere in the course of the past few years were also considered and are acknowledged in the full text. Interestingly, a few new insights that have not been cited before have emerged during the preparation of the guidelines. The most important new feature is the presentation of a ‘rating system’ for NGS-based diagnostic tests. The guidelines and statements have been applauded by the genetic diagnostic community, and thus seem to be valuable for the harmonization and quality assurance of NGS diagnostics in Europe.
For immediate release
The proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) negotiations, currently at the stage of tripartite negotiations between the Council (representing Member State governments), the European Parliament, and the European Commission, still risks restricting the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (19 October 2015) in a statement issued by a range of organisations representing geneticists and patients.
Sequencing technologies generate data on the entire sequence of the human genome for a decreasing price at increasing speed. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. After a consultation of the ESHG membership (in Febr/March 2014) the Public and Professional Policy Committee of the European Society of Human Genetics in collaboration with the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform developed recommendations on NGS for NBS that were published online the 28th of January 2015. The main messages is that the primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood.
Access the EJHG Article
In a letter published in the journal Science on 30 August, Professor Martina Cornel, chair of the Professional and Public Policy Committee of ESHG and colleagues call for restraint in the use of diagnostic testing based on whole-genome sequencing. Wherever possible, such testing should be restricted to those genome regions linked to the patient's indications, they say, and wider testing needs to be justified in terms of necessity. Adding additional targets to a diagnostic test would be a violation of this, they say.
However, in the case of unsolicited findings, the patient's right not to know may sometimes have to be secondary to clinical geneticists' professional responsibilities, say the authors. The patient may not have foreseen a specific finding and in some cases the physician will have a moral duty to warn close relatives. Pending further debate, a cautious approach continues to be warranted, they say.
Letter in Science (for subscribers only)
The letter by Carla van El et al summarises the Recommendations of the ESHG concerning on Whole Genome Sequencing in Health Care (Recommendations and Background Document) published in the European Journal of Human Genetics
The Letter to the editor in reaction to Wolf SM, Annas GJ, Elias S. Patient Autonomy and Incidental Findings in Clinical Genomics. Science 340,1049-1050 (2013).
ESHG calls for prudent use of WGS-based testing
Van El CG1 & Dondorp WJ4, De Wert GMWR3,4, Cornel MC1,2,3 (on behalf of the ESHG Public and Professional Policy Committee)
(1) Section Community Genetics, Department of Clinical Genetics and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands
(2) Center for Medical Systems Biology, Leiden, the Netherlands
(3) Centre for Society and the Life Sciences, Nijmegen, the Netherlands
(4) Department of Health, Ethics and Society; Research Schools CAPHRI & GROW, Maastricht University, Maastricht, the Netherlands
In their Policy Forum contribution Patient autonomy and incidental findings in clinical genomics Susan Wolf et al. criticize the American College of Medical Genetics (ACMG) for giving up on well-established principles of patient autonomy and informed consent. The European Society of Human Genetics (ESHG) recently also called for more prudence. The ACMG presents WGS-based diagnostic testing as an opportunity for screening. The ESHG position is that whenever possible, such testing should be targeted to genome regions linked to the indication. Wider testing requires a justification in terms of necessity and proportionality. Adding screening targets to a diagnostic test violates the necessity criterion. Imposing this extra testing upon patients who need an answer to their clinical problem is at odds with respect for autonomy. As stated by Wolf et al., people have a right to decline testing on the basis of their own assessment of burdens and benefits. However, with regard to reporting unsolicited findings, the ESHG does acknowledge that the patient's ”˜right not to know' may sometimes have to give way to professional responsibilities with regard to the interests both of the patient himself (who may not have foreseen and considered a specific finding) and of his close relatives (”˜duty to warn'). Where testing of children is concerned, the child's best interest may override the parental ”˜right (not) to know'. Pending further debate, we urge a more cautious attitude specifically including the patients' and physicians' perspectives.
 S.M. Wolf, G.J. Annas, S. Elias. Patient Autonomy and Incidental Findings in Clinical Genomics. Science 340,1049 (2013).
 C.G. van El et al. Eur J Hum Genet., 21, 580 (2013).
 W. Dondorp, B. Sikkema-Raddatz, C. de Die-Smulders, G. de Wert, Hum Mutat., 33,916 (2012).
The decision by the US Supreme Court to rule that human genes cannot be patented has important implications for patients and for science. The patents held by Myriad Genetics on the BRCA 1 and 2 genes which predispose to breast and ovarian cancers has meant that the company was free to set a price for the diagnostic test. That price was often beyond the reach of many of those who needed to be tested. Now the field will be open, and other laboratories will be able to provide the genetic diagnosis. This should result in lower costs and greater access. Of course, the decision in the US does not affect the legal situation in Europe, where genes are still patentable. However, it is noticed that the arguments, that were used to convince the Supreme Court, were very similar to the ones put forward by the ESHG in its recommendations on patenting and licensing in genetic testing, issued in 2008.
“The Supreme Court has concluded that human genes can only be discovered, not invented”, said Gert Matthijs. “and discoveries cannot be patented, also according to European patent law. More importantly, in the decision, it is specifically stated that genes and the information they encode are not patent eligible. Thus, it is acknowledged that genes are not just chemical structures, but that they are recognized for their genetic content. That's exactly how geneticists deal with them.” By the same token, the Supreme Court held that cDNA - which is actually an artificial copy of a messenger RNA - can still be patented, because it does not exist in nature. That's a twist, which is useful to safeguard patent protection on possible therapeutic uses of gene products, but which will in practice not significantly interfere with DNA diagnostics.
See also: ESHG Recommendations on Patenting and Licensing in Genetic Testing
Download the ESHG Position Statement on the Inclusion of an Article on Genetic Testing in the Proposed Regulation on in-vitro Diagnostic Devices.
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. However, it can also pose major ethical problems if used incorrectly, say new recommendations from the European Society of Human Genetics (ESHG) published on line today (16 May 2013) in the European Journal of Human Genetics (http://www.nature.com/ejhg/journal/v21/n1s/index.html).
Many services based on whole genome and on exome* sequencing and analysis are now available to patients at an affordable price, and this raises the question of how to ensure that they are provided appropriately. “Such sequencing generates huge amounts of information that needs to be processed, analysed, and stored in a responsible manner”, said Professor Martina Cornel, chair of the Professional and Public Policy Committee of ESHG. “It is preferable to use sequencing or analysis specifically targeted at a particular health problem to avoid unsolicited findings, or those that cannot yet be interpreted, which can cause considerable anxiety to patients and their families. Clear guidance on how to deal with such findings is needed.
”Targeted analysis will limit such unsolicited findings, says the ESHG, and this is particularly important at present when there are only a limited number of clinicians properly trained to inform patients on the significance of the results of GWAs and exome sequencing. While the Society believes that the duty to inform patients may outweigh their right not to know in some circumstances, the new recommendations propose that analysis should be limited to genome regions linked to the clinical problem for which the analysis is being undertaken.
“We are opposed to the type of opportunistic screening that throws up large numbers of incidental results. If such results reveal a treatable or preventable condition, then clearly it is advantageous to patients to be informed about them. But in the majority of cases it is very difficult to interpret exactly what such incidental results mean for patients and their families. The evidence currently available often comes from families with affected persons, but it is lacking on the interpretation of results in other situations. Furthermore, in genetics healthcare, autonomy is considered very important: patients should be allowed consent on what would be screened for and reported to them. We believe that it is premature today to look for such results other than the clinical problem in circumstances where there are no prior clinical indications or family history ”, said Professor Cornel.
“A sustained effort to educate clinicians in genetics is needed in order to be able to cope with advances in analysis. We also believe that the Society has an important role to play in raising awareness of genetics among the general public. Only with the benefit of a general increase in genetic literacy can society become properly involved in the debate over who has the right to know what and in which circumstances,” she said.
Professor GertJan van Ommen, Editor in Chief of the European Journal of Human Genetics, said: “The importance of this issue has been underlined by the US Government's Bioethics Advisory Panel's plans to report on how incidental findings encountered in genomics research should be handled. I believe that ESHG has made an important contribution to the debate, which will be further discussed at their conference in Paris in June.”
*Exomes are the short sequences of DNA representing the regions in genes that are translated into protein
Wednesday, October 31, 2012
In response to the on-line publication by the European Journal of Human Genetics today (Wednesday) of an article by US researchers led by Dr. Robert Cook-Degan, a former member of the US Office of Technology Assessment, showing that Myriad Genetics, providers of the BRCA1/2 genetic test in the US, has amassed vast quantities of clinical data without sharing it, Professor Martina Cornel, chair of the European Society of Human Genetics' Professional and Public Policy committee, said:
“We are very concerned that such important data is being withheld from those who most need it. Interpreting the variants of unknown significance (VUS) that may be found on analysing the patient's genome plays an essential part in being able to provide proper counselling and if necessary, preventive or therapeutic guidance. By not sharing their data on the VUS obtained from individuals undergoing BRCA1/2 testing, where Myriad is the sole commercial provider of a test in the US, geneticists have been unable to develop the up-to-date algorithms that are necessary to best interpret the effects of genetic variants. While Myriad has access to public databases in order to help interpret their VUS results, this is currently not reciprocal.
“We know that, regrettably, medical geographic inequities are common, but what is particularly worrying about this situation is that it is the first time that such inequities have been based on a lack of access to clinical information, rather than lack of a product. Myriad's stated aim to enter the European market more vigorously may lead to unfair competition with academic institutions for predictive precision. It is vital that progress towards personalised medicine, which holds out so much promise, is not hindered by companies maintaining private genomic databases. Policymakers should take an urgent look at the regulatory and reimbursement issues involved in genomic testing in order for all the data that is essential to understanding the clinical significance of VUS to be made public, to the benefit of patients and healthcare providers alike.”
View the paper
Wednesday, June 13, 2012
The use of genetic testing to establish racial origins for political purposes is not only scientifically foolish, but also unethical and should be condemned, the European Society of Human Genetics (ESHG) said today (Thursday June 14). The society, which promotes research in basic and applied human and medical genetics and ensures high standards in clinical genetic practice, said that the use by a member of parliament from the Hungarian far-right Jobbik party of a genetic test to attempt to prove his ”˜ethnic purity' was ethically unacceptable.
The company Nagy GÃ©n scanned 18 positions in the MP's genome for variants that it said were characteristic of Roma and Jewish ethnic groups and concluded that Roma and Jewish ancestry could be ruled out.
Professor Joerg Schmidtke, President of ESHG, said on behalf of the Executive Board: “This is a gross distortion of the values of genetic testing, which is intended to be used to diagnose disease rather than to claim racial purity. In addition, the test proves nothing; it is impossible to deduce someone's origins from testing so few places in the genome. I am sure that clinical geneticists worldwide will join me in condemning this scandalous abuse of a technology that was developed to help the sick, rather than to promote hatred.”
Professor BÃ©la Melegh, President of the Hungarian Society of Human Genetics added: “We were shocked to hear that a laboratory authorised to carry out genetic analysis for diagnostic purposes carried out such a test. Not only does it not serve a diagnostic purpose, but it has been used to create tension between people of different ethnic origins. We are asking the Hungarian government to prosecute the company concerned under the 2008 law on genetics, and to take action to ensure that similar abuse of genetic testing cannot take place in our country in future.”
The 2012 European Genetics Conferences in Nuremberg, Germany (June 23-26) will provide a further opportunity for the ESHG to denounce such an unethical perversion of genetic science, and insist, at the same time, on the importance of genetic testing in the medical or scientific context of good practice.
NIPT - Background document including Recommendations:
Dondorp W, De Wert G, Bombard Y, Bianchi DW, Bergmann C, Borry P, Chitty LS, Fellmann F, Forzano F, Hall A, Henneman L, Howard HC, Lucassen A, Ormond K, et al, on behalf of the European Society of Human Genetics (ESHG) and the American Society of Human Genetics (ASHG). Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur J Hum Genet 2015;23:1438-1450.
NIPT - Summary and Recommendations:
Dondorp W, De Wert G, Bombard Y, Bianchi DW, Bergmann C, Borry P, Chitty LS, Fellmann F, Forzano F, Hall A, Henneman L, Howard HC, Lucassen A, Ormond K, et al, on behalf of the European Society of Human Genetics (ESHG) and the American Society of Human Genetics (ASHG). Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Summary and recommendations. Eur J Hum Genet advance online publication 1 April 2015; doi: 10.1038/ejhg.2015.56
Responsible implementation of expanded carrier screening – Background document including Recommendations of the European Society of Human Genetics
Henneman L, Borry P, Chokoshvili D, Cornel MC, van El CG, Forzano F, Hall A, Howard HC, Janssens S, Kayserili H, Lakeman P, Lucassen A, Metcalfe SA, Vidmar L, de Wert G, Dondorp WJ, Peterlin B, on behalf of the European Society of Human Genetics. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016;24:e1-e12.
Responsible implementation of expanded carrier screening - Summary and Recommendations:
Henneman L, Borry P, Chokoshvili D et al: Responsible implementation of expanded carrier screening: Summary and recommendations of the European Society of Human Genetics. Eur J Hum Genet 2016; 24: 781–783.
This leaflet gives patients information about genetic tests that target many different genes at once. The information may help you to decide whether or not to have the test and help you to understand the results.
The recommendations of the European Society of Human Genetics on Whole Genome Sequencing in the European Journal of Human Genetics (2013) 21, 580–584; doi:10.1038/ejhg.2013.46
The Background Document on ”Genetic testing and common disorders in a public health framework: how to assess relevance and possibilities" has been published in the European Journal of Human Genetics 2011;19:S6-S44. Click here
The Recommendations of the ESHG on ”Genetic testing and common disorders in a public health framework" have been published in the European Journal of Human Genetics 2011;19:377-81. Click here
Genetic testing in asymptomatic minors: Recommendations of the European Society of Human Genetics. (Cornel M as collaborator) Eur J Hum Genet. 2009 Jun;17(6):720-1. Click here
The European Society of Human Genetics published Background considerations towards ESHG Recommendations on genetic testing in asymptomatic minors in the European Journal of Human Genetics 2009; 17: 711 - 719. Click here
In addition the Recommendations on genetic testing in asymptomatic minors were published in the European Journal of Human Genetics 2009; 17:720-1. Click here
by Milan Macek Jr., president-elect of the ESHG
In 2002 ESHG set down an ad hoc committee on the recognition of clinical genetics as an European speciality. During this process a collaboration with the European Union of Medical Specialists (UEMS.net) led to the development of a document outlining the qualifications needed to obtain the speciality, and the establishment of a Multidisciplinary Joint Committee Clinical Genetics in UEMS with representatives of the ESHG ad hoc committee as members. The guidelines, which previously, after discussions with the chairs of the national societies at several meetings during ESHG meetings, had been endorsed by ESHG and, finally, this year by the Boards and Sections and the Council of UEMS.
The endorsed guidelines can be found here.
Please contact Dr Ulf Kristoffersson
- The European Society of Human Genetics (ESHG) wants to involve the genetics community in the analysis of, and the discussions on, the practical, political, societal, ethical and economical aspects of patenting and licensing of genes, sequences and genetic tests. More
- Eurogentest has prepared Recommendations for genetic counselling related to genetic testing. The recommendations were written by Eurogentest Unit 3 partners and experts, circulated for comments and endorsement among ESHG membership and European National Human Genetic Societies and finally sent to ESHG Board for endorsement.
The recommendations can also be found on the Eurogentest website.
Recommendations on the following topics are available in the European Journal of Human Genetics
- Patenting and licensing in genetic testing: ethical, legal and social issues - More
- Provision of genetic services in Europe: current practices and issues - More
- Population genetic screening programmes: technical, social and ethical issues - More
- Data storage and DNA banking for biomedical research: technical, social and ethical issues - More
- Genetic information and testing in insurance and employment: technical, social and ethical issues - More
- The need for interaction between assisted reproduction technology and genetics (Recommendations) - More
- The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues (Background Document) - More
- Polymorphic sequence variants in medicine: Technical, social, legal and ethical issues Pharmacogenetics as an example (Draft Background Document) - More
ESHG response to the European Parliament Report on the ethical, legal, economic and social implications of human genetics.