The European Society
of Human Genetics

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Press Releases

Please note that press releases will be published as soon as the embargoes have expired, starting with 00.01 hrs CEST, Saturday, June 12, 2010.


Direct-to-consumer genetic tests neither accurate in their predictions nor beneficial to individuals, European geneticists say

Embargo:  00.01 hrs CEST Tuesday 31 May 2011

Amsterdam, The Netherlands: Direct-to-consumer (DTC) genetic tests give inaccurate predictions of disease risks and many European geneticists believe that some of them should be banned, the annual conference of the European Society of Human Genetics will hear today (Tuesday).  In the first of two studies to be presented, Rachel Kalf, from the department of epidemiology at Erasmus University Medical Centre, Rotterdam, The Netherlands, will say that her research is the first to look at the real predictive ability of such tests, the results of which are available directly to an individual without having to go through a healthcare professional.

Working under the supervision of Associate Professor Cecile Janssens, together with researchers from Leiden, The Netherlands, and Boston, USA, Ms Kalf examined the risk predictions supplied by two large DTC companies, deCODEme (Iceland)  and 23andMe (USA).  They simulated genotype data for 100,000 individuals based on established genotype frequencies and then used the formulas and risk data provided by the companies to obtain predicted risks for eight common multi-factorial diseases - age-related macular degeneration (AMD), atrial fibrillation, celiac disease, Crohn's disease, heart attack, prostate cancer, and Type 1 and Type 2 diabetes (T2D).

Although the predictive ability of the DTC tests in the study was moderate for all diseases, both companies assigned an increased risk to a substantial part of the group.  Yet the risk of disease in this group was often not substantially higher than the risk in the rest of the population studied.  For AMD, the disease with the highest predictive ability, both companies assumed that the risk in the population was around 8%.  Of all subjects designated as having an increased risk, 16% using the 23andMe risk estimations and 19% using deCODEme's estimations would develop AMD, compared to the 4% found in the rest of the population studied.  

“So individuals in the increased risk group may have a four-fold increased risk of disease, but they are still far more likely not to develop the disease at all.  For T2D, where the companies calculated the average risk at around 25%, 32% of those assigned to the increased risk group would actually develop T2D compared to 22% in rest of the study population.  This difference in disease risk is too small to be of relevance”, said Professor Janssens.

“deCODEme predicted risks higher than 100% for five out of the eight diseases”,  Ms Kalf will say.    “This in itself should be enough to raise considerable concern about the accuracy of these predictions - a risk can never be higher than 100%.  In the case of AMD one in every 200 individuals in the group would have received a predicted risk of higher than 100%, suggesting that they would definitely develop the disease.”

The DTC companies have been criticised for giving an exaggerated and inaccurate message about the connection between genetic information and disease risk.   “They only take genetic factors into account when predicting risks for consumers, whereas in most multi-factorial diseases other modifiable risk factors, such as diet, environment, exercise and smoking have a much stronger impact on disease risk”, said Professor Janssens.  “We are all aware of the ethical problems surrounding DTC genetic testing, but this study also confirms that their predictions are inaccurate.   At a time when some governments are considering regulating such tests, we believe that we have made an important contribution to the debate”, she concluded.

In the second study, Dr. Heidi Howard from the University of Leuven, Belgium, and her colleague Professor Pascal Borry reported the results of a survey of a representative sample of clinical geneticists from 28 countries across Europe on their experience of and attitudes to DTC genetic testing.   “This is the first ever survey of European clinical geneticists on the subject”, Dr. Howard will say, “and the results were conclusive - 69% of respondents felt that prenatal gender tests should be legally banned, and 63% wanted to proscribe whole genome scans carried out by DTC companies.”

One of the problems with DTC tests is that the companies' tendency to overstate the potential of predictive information does not help to produce a public properly educated about the potential value and limitations of genetic information.  This is particularly true when it comes to whole genome scans, where a lot of results are given for many different conditions, the researchers say.

“Clinical geneticists' concerns with DTC genetic tests are mostly related to the fact that these tests usually lack clinical validity and utility. Moreover, these tests are usually carried out without the provision of genetic counselling. According to the experiences of clinical geneticists, patients often do not know how to interpret the results they receive and are often confused by them. However, almost all clinical geneticists feel that they have a duty to provide counselling if patients contact them after having purchased a DTC genetic test,” says Dr. Howard.

“A person who undergoes a genetic test has to be accompanied - explanations, physical aid, the right to choose whether to know or not - and this is not true in the case of direct access to such a test”, said one survey respondent.

“Genome-wide scans by companies are totally unacceptable, as they can derive sensitive information about medically relevant conditions and will also provide lots of information which is difficult to interpret, even for medical professionals”, said another respondent.   Presenting the results of such tests directly to individuals is unacceptable, the majority of those surveyed said.   

90% of respondents felt that a pre-symptomatic test - predicting if an asymptomatic person had a very high probability of developing a condition - should not be allowed without face-to-face medical supervision; 93% felt the same for a predictive test for a condition that has a penetrance (the proportion of individuals with the mutation who exhibit clinical symptoms) of 50 - 60%; 79% for a carrier test for homozygous monogenic disorders, such as sickle-cell anaemia; and 72% for a predictive test for a condition that increased or decreased a person's risk of developing it by 4% when compared to the general population.

At the moment, DTC genetic tests reach the market without having undergone any form of regulation.  “Better regulation is needed at the level of market introduction of these tests”, says Professor Borry.  As in the case of drugs, a procedure should be developed for genetic tests.”

Currently only a few European countries, for example France and Switzerland, have legislation that states that genetic tests can only be accessed via individual medical supervision.  “Although this model is sometimes criticised for being too paternalistic”, says Professor Borry, “in the absence of a good working pre-market control of genetic tests, it could be a useful way of responding to some of the concerns over DTC testing.”

The provision of genetic testing services outside the regular healthcare system can also lead to unnecessary visits to healthcare providers and hence an increased burden on healthcare resources, the researchers say.


Abstract nos :   C14.5 (Kalf) and C14.3 (Howard) Tuesday, May 31, 2011, 11:00 am

Note:   When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.

Notes for editors:  The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe.   It currently has about 1600 members from 66 countries.   About 2500 delegates are expected to attend this year's conference.

New gene makes the difference in Usher syndrome

New gene makes the difference: genetic modifier in Usher Syndrome explains variability in symptoms and will lead to better diagnosis

Usher syndrome (USH), an inherited condition involving both hearing and vision loss, is not simply a recessively inherited disease, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Saturday).  Dr.  Hanno Bolz, Associate Medical Director of the Bioscientia Centre for Human Genetics, Ingelheim, Germany, and active in teaching and research at the University Hospital of Cologne, will say that his team's research challenges the traditional view that USH was inherited as a single gene disorder, and shows that it may result from at least two different genetic mutations.    This could lead to more accurate diagnosis of this condition, which is responsible for up to 10% of all cases of childhood deafness and 50% of all deaf/blindness in adults.

Some USH patients have only one mutant copy of an Usher gene, which in itself is insufficient to explain a recessive disease, and there is often an unexplained variability of the visual characteristics of the condition, even between close family members.  Dr. Bolz's team, including scientists from Cologne University, Germany and zebrafish researchers from the University of Oregon, USA, decided to look for additional USH genes and genetic modifiers that could be involved in disease causation.

“We became interested in researching sensory diseases such as Usher syndrome because they can be very debilitating and affect people at a young age”, said Dr. Bolz.  “Despite extensive research into USH, there is currently no effective treatment for it.”

Apart from linkage studies of recessive disease, where a particular trait or disease characteristic is traced within a family, another way of identifying genes linked to disease is to analyse genes that encode proteins which are similar to the proteins involved in the disorder being studied.   Using a genome-wide database search, the team identified a gene, PDZD7, which encoded a protein with striking similarity to the proteins whirlin and harmonin, both known to be involved in USH.

“We found that some patients with only a single mutation of the gene responsible for the condition, GRP98, also had a mutant copy of PDZD7, and that this gene interacts with proteins involved in USH”, said Dr. Bolz.  “We were able to validate these findings in transgenic zebrafish, and to show that PDZD7 localises to cilia, thus providing further confirmation that USH is a retinal ciliopathy.”

Cilia are antenna-like protuberances that project from cells and are often involved in sensory activity such as vision, hearing or smell.   Genetic mutations can affect their proper functioning, and these defects in turn affect critical signalling pathways essential to cell development.   As a result, cilia defects are involved in many diseases which produce multiple symptoms.

Diagnosis of USH is complicated, the scientists say.  At present it is normally related to clinical symptoms, such as childhood hearing impairment and the vision disease retinitis pigmentosa in the first or second decade of life.  Retinitis pigmentosa affects the layer of light-sensitive tissue in the retina and vision loss occurs as the light-sensing cells gradually deteriorate, causing blind spots which eventually merge to produce tunnel vision and sometimes total blindness.

“When hearing and visual loss are both present, the most likely diagnosis is Usher syndrome”, said Dr. Bolz.  “More precise genetic diagnosis is essential, but the genes are large and not easily accessible to genetic testing.  However, by considering clinical data of the patient and the background of his/her family - ethnicity, for example - one can apply efficient testing strategies.  For the parents of a deaf child, it would be advantageous to be aware of the retinal degeneration that will occur later on.  

“Research on new Usher genes must therefore be translated quickly into genetic testing in order to aid parents to choose appropriate therapies to diminish the later consequences of the disease,” he said.  The decision to opt for a cochlear implant, for example, could be influenced by the knowledge as to whether the causative mutation is in a gene for isolated deafness or in a USH gene.

“We believe that our work may serve as a paradigm for the future”, said Dr. Bolz.  “In many recessive diseases, variability of disease characteristics is the rule rather than the exception, and in most cases this phenomenon is unexplained.   With advances in new sequencing techniques that permit simultaneous analysis of several genes, we will need to interpret variants in all Usher genes in a patient, not only in one.   Two hits in a single Usher gene may explain the disease in a patient, but not its variability.   Our research is a step on the road to understanding that variability and to being able to provide an accurate prognosis of disease progression.”

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Understanding genetic mixing through migration

Understanding genetic mixing through migration: a tool for clinicians as well as genealogists

Gothenburg, Sweden: Understanding the genetic ancestry of mixed populations, such as those found in North America, can not only help to detect their origins but also to understand the genetic basis of complex diseases, a scientist will tell the annual conference of the European Society of Human Genetics today (Saturday June 11).     It is the first time that the genomes of individuals of admixed ancestry have been sequenced in such detail, says Dr. Francisco De La Vega of Life Technologies, Foster City, California, USA.

Working with Professor Carlos Bustamante and his team in the Department of Genetics at Stanford University, the scientists analysed the genomes of two people - one of African-American and one of Hispanic-Latino origin.    The majority of the personal genomes sequenced to date come from individuals of either European, African, or Asian descent, because it is in these groups that most genetic disease association studies are being carried out.   However, populations where genetic mixing through migration has taken place relatively recently make up a sizable proportion of the world's population, and have been not been well studied to date because of the complexity of dealing with the contributions of genes from different ancestries in disease.

“We set out to provide a better understanding of the genome structure in admixed populations by sequencing one African-American and one Mexican sample”, said Dr. De La Vega.  “By analysing genetic variants in mixed people whose frequency differs in the ancestral populations, we can work out the ancestry of different chromosomal segments in an individual.   This has already been done in a number of different ways.   The difference with our work is that, by using whole genome sequencing using the SOLiDâ„¢ System, we can greatly increase the resolution of our analyses and achieve a very much clearer picture of the ancestry of genome sequences for the individuals studied.

“We already know that present-day African-Americans trace their ancestry to a rich mosaic of migrants from the mainly West African and Northern European populations who settled in North America and the Caribbean.  Mexicans, on the other hand, are descendants of Meso-American indigenous populations - themselves derived from population migrations from Asia (through the Bering straits) - and largely Southern European (mainly Spanish) settlers”, said Dr. De La Vega.  “But the added value of our research is that we can show the approximate number of generations at which the genetic mixing occurred, estimate the rate at which admixture occurred, and understand better the genetic diversity in the ancestral populations.”

To date there are few comprehensive studies of genetic diversity in native populations in the Americas, and by analysing them scientists can begin to piece together the population history of both the admixed and indigenous populations.   They can also begin to analyse the contribution of native American genetic variants to the disease burden in the Americas of today, something which at present is relatively unknown.

“We believe that our work will help move forward genetic disease association studies in these admixed populations”, said Dr. De La Vega. “This would not only provide valuable information on the genetic component of disease in these people, but would also help refine genetic association findings in other populations by replicating the findings in admixed samples.   And the high resolution admixture maps we can generate can help in studies to map variants of disease whose prevalence is very different in the ancestral populations of admixed groups.”

The scientists intend to follow up their work by sequencing many more genomes of different populations in the Americas in order to understand further differentiation within the continent and the frequency of the genetic variants. “The decreasing costs of sequencing genomes through new sequencing instruments such as those developed by Life Technologies, is making possible for the first time to compare at large scale genetic variants among and within populations” said Dr. De La Vega.

The scientists are also participants in the 1000 Genomes Project, an international research effort to sequence the genomes of at least 1000 subjects from a number of different ethic groups, and thus establish the most detailed catalogue of human genetic variation to date. 

“The Project will sequence the genomes of around 500 admixed individuals from diverse populations including African-Americans from the South West and South East US, Afro-Caribbeans from Barbados, Mexicans from Los Angeles, Peruvians from Lima, Colombians from Medellin, and Puerto Ricans from Puerto Rico.  We are incredibly excited about the inclusion of these populations in the Project, since we hope that the genomic resources developed by it will encourage the development of genetic studies in under-represented communities in the US and Latin America”, said Professor. Bustamante, co-director of the study.  “In the long run, the information obtained from such studies could become the basis of personalised genomic therapies for individuals of admixed origins.”

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Smell holds the key to early diagnosis of Parkinson's

Sense of smell holds the key to diagnosis and treatment in early-stage Parkinson's disease

Gothenburg, Sweden:  A fast, simple and non invasive test of the ability to smell may be an important tool to screen people who are likely to develop Parkinson's disease (PD), in which motor symptoms only become evident at a later stage of the disease, a German scientist will tell the annual conference of the European Society of Human Genetics today (Saturday).   Dr. Silke Nuber, from the Department of Medical Genetics, University of Tübingen, Germany, will say that her team's research could help in the development of treatments for the early stages of the disease.

Dr. Nuber and colleagues from Germany, Switzerland, and the UK, decided to study transgenic mice with high levels of human alpha-synuclein, a protein known to be crucial in the development of PD.   Alpha-synuclein can be turned off in these animals by administration of an antibiotic, allowing scientists to look at the reversibility of neuropathological alterations.    “The mice expressed alpha-synuclein primarily in neurons of the olfactory bulb”, said Dr. Nuber, “and we therefore expected to find alterations in smell-related behaviour in these animals.   Since one of the earliest symptoms in PD patients is a reduction in the sense of smell, we felt that these mice could mimic the early stages of the disease.”

Parkinson's disease is a degenerative disorder of the central nervous system that affects the control of motor skills, speech, mood and behavioural problems, and cognitive functions. It is characterized by muscle rigidity, tremor, and slowing or loss of physical movement.    It is a chronic, progressive condition and there is currently no cure.

The scientists tested the sense of smell of the transgenic mice by analysing their behaviour when exposed to a new scent, for example the male mice were exposed to the scent of female mice.   They then looked at neurotransmitter activity in different areas of the brain and found a malfunction of dopamine regulation.

When expression was blocked in middle-aged mice, the dopamine level was comparable to those of wild-type (normal) animals, implying both direct influence of transgenic expression on dopamine levels, and the reversibility of symptoms. Dopamine receptors are involved in a number of neurological processes, and abnormal dopamine receptor signalling is known to be implicated in PD.   “We believe that we have developed one of the first models to show this olfactorial dopamine deficit without additional abnormalities in the nigrostriatal pathway”, said Dr. Nuber.

The nigrostriatal pathway is one of the major dopamine pathways in the brain, and is particularly involved in the control of movements.   Loss of dopaminergic neurons in the substantia nigra, a structure located in the midbrain, is one of the main features of PD, but the motor symptoms of the disease do not show themselves until more than half of the dopamine function has been lost.  Being able to identify the early stages of dopaminergic dysfunction is therefore particular important both for diagnosis and treatment of PD.

The scientists also carried out a fear-related smell test, in which the animals would normally have been expected to remain motionless because they sensed the presence of a predator.   However, the mice showed reduced anxiety in this test.   “In animals with olfactory bulbectomy - a suppression of the sense of smell - hyperactivity and increased exploratory behaviour are strong markers of behavioural alterations”, said Dr. Nuber.    “These animals model depression and anti-depressive drugs can ameliorate their depressive symptoms.”
Increased exploratory behaviour may diminish the anxiety and depressive signs in new surroundings that would be normal for mice lacking any sense of smell.  The researchers therefore surmised that this behaviour might also exist in mice with a reduced dopamine transmission in the olfactory bulb.   “It would be interesting to study whether early treatment with anti-depressive drugs might increase odour sensitivity in PD patients”, said Dr. Nuber.  At present, diagnosis of PD is based entirely on the motor symptoms which appear at a later stage, and all drug treatments have been approved for use only at this stage. 
The researchers say that it would be worthwhile to develop some standardised tests for testing smell function.   “We don't know whether the existing drugs used at a later stage in PD would be effective in the earlier phases of the disease, but having an early biomarker would enable us to try to develop different treatment strategies”, said Dr. Nuber.   “Based on what we know now, the clinical definition for the diagnosis of PD should not rely solely on the diagnosis of motor symptoms.   It would be helpful to test the ability of olfactory detection and learning.   Even if we cannot preserve olfactory structures and functioning, it will enable us to diagnose the disease earlier on and also help with the development of treatment strategies to halt or even reverse the underlying disease process in PD.  

“We believe that detailed functional imaging analyses paralleled by behavioural studies in the mouse model could lead to the development of an efficient preclinical therapy that can be used to halt the massive dopaminergic neurodegeneration that takes place in human PD patients”, she concluded.

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Personalised therapy for Hepatitis C a step closer

Small genetic variant can predict response to hepatitis C treatment; may spare side effects to those in whom treatment would be ineffective

Gothenburg, Sweden: A small genetic change can predict how people infected with hepatitis C react to treatment, paving the way to personalised therapy for this difficult to treat disease, the annual conference of the European Society of Human Genetics will hear today (Sunday 13 June).  Dr.  Zoltan Kutalik, from the Department of Medical Genetics, University of Lausanne, Switzerland, will tell delegates that individuals with this change, in a gene encoding for the antiviral cytokine (cell-signalling molecule) interferon lamda, reacts less well to treatment.  This knowledge could spare them the unpleasant side effects of a therapy which most likely would have little benefit for them, he says.

Hepatitis C is a serious liver disease, normally contracted through drug use, blood transfusion or sexual transmission.  About 10% of all patients have no identifiable source of infection.  The virus produces chronic infection in around 80% of infected individuals, and half of these do not respond to existing therapies.   Current treatment involves a combination of an interferon and the antiviral medication ribavirin.   Side effects are common and can be serious to the extent that some people are unable to continue to work.

The fact that people respond so differently to the same treatment is usually because a genetic variation in the non-responders is, via complex genetic pathways, inhibiting the effects of therapy.    “The Lausanne University Hospital (CHUV) has a large cohort  of Hepatitis C patients seen at the hospital over many years”, said Dr. Kutalik, “so this provided the opportunity for us to do a genome-wide association study on 1362 of them to see if we could track down any differences relating to patients' failure to respond to therapy.”

Genome-wide association studies look at variations across the entire genome of individuals to look for genetic associations with well-defined traits, including why some people get a particular disease and condition as well as why they might react or not to therapy for it.   In this case, approximately half of the patients studied had responded successfully to therapy, giving the scientists the opportunity to compare their genomes with those from patients who had not responded.

“Using a gene-chip technology, a team of clinicians, geneticists and statisticians looked at over one million polymorphic nucleotides, the letters A, C, G and T of the DNA sequence”, said Dr. Kutalik.  “Our analysis revealed that a single nucleotide polymorphism, or SNP, was present in a gene called IL28B, which encodes for interferon lambda.   This was significantly associated with both natural and drug-induced clearance of the hepatitis C virus from the body. This polymorphism may exert its influence by modulating the expression level of the interferon lambda gene.”

Individuals who carry the protective allele (letter) at this genetic locus are twice as likely to clear the virus and, even if they do not, they will respond to therapy in a sustained manner; the scientists say.  “Individuals infected with the less malignant subtype of the virus and carrying no risk allele were five times more likely to respond than those who were infected with other subtypes and who carried at least one copy of the risk allele.  Based on our results we can speculate that the interferon lamda gene is key to increasing the success of therapy, as such therapy could, in theory, compensate for the effect of the polymorphism. Phase 1B trials of interferon lamda therapy in patients with hepatitis C have already shown promising results”, Dr. Kutalik said.

The scientists intend to follow up their work by focusing on a better understanding of the more complex characteristics of hepatitis C, including finding the genetic variants that are responsible for hepatitis C liver fibrosis.    “This disease affects up to 300 million people worldwide.   It is insidious, and often individuals are not aware that they are infected until serious liver damage has taken place”, said Dr. Kutalik. “Finding better treatments is vital.   As well as sparing those who would not react well to current treatment from side effects, we hope that our work may provide pointers to the development of effective therapies for the future.”

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Do study participants have the right to know?

Children born after assisted reproduction at greater risk of congenital malformations; doctors should be prepared to inform parents of these risks, scientists say

Gothenburg, Sweden:  Couples considering undergoing assisted reproductive technology (ART) treatment should be informed about the increased risk of congenital malformation posed by the use of ART, the annual conference of the European Society of Human Genetics will hear today (Monday).  Dr. Géraldine Viot, a clinical geneticist at the Maternité Port Royal hospital, Paris, France, will say that she believed that most doctors working in ART clinics in France only told couples about such risks if they were asked specific questions.

Dr. Viot and colleagues conducted a survey in 33 French centres registered for ART, around one third of the total number of clinics registered to perform ART procedures in France. All ART births from these clinics from 2003 to 2007 were included; 15 162 children in total.   The study was the largest to date on this subject.  Questionnaires were completed both by the parents and the paediatrician and the prevalence of malformations found compared with the data obtained from national registers and in published papers.

“We found a major congenital malformation in 4.24% of the children”, said Dr. Viot, “compared with the 2-3% that we had expected from previous published studies. This higher rate was due in part to an excess of heart diseases and malformations of the uro-genital system.   This was much more common in boys. Among the minor malformations, we found a five times higher rate of angioma, benign tumours made up of small blood vessels on or near the surface of the skin.   These occurred more than twice as frequently in girls than boys.”

However, the scientists say, their results are a long way from the 11% of major malformations that have been reported by some studies.  “Given that our study is the largest to date, we think that our data are more likely to be statistically representative of the true picture”, said Dr. Viot.

The average age of the parents of children born with malformations was not statistically different from the other parents in the ART group.  The origins of the malformations are probably multiple, says Dr. Viot.  “We need more research in order to understand the relationship between embryo culture media, timing of embryo transfer, the effects of ovarian stimulation, the use of ICSI, where sperm is injected directly into the egg, freezing of gametes and embryos and these disorders.   

“We estimate that in France some 200 000 children have been born after ART and therefore a malformation rate of this magnitude is a public health issue.   It is important that all doctors and also politicians are informed about this.   We also need to follow up all children born after ART and to put much more effort into trying to understand which of the procedures involved is implicated in this problem.”

Dr. Viot and colleagues intend to follow up their work analysing a further 4000 questionnaires, from children born in 2008, and to look at the motor development of children born in 2003, who are now aged 7.   “By following all these children we hope to understand more about not only what can go wrong after ART, but why it goes wrong”, she said.  “At a time when infertility is increasing and more and more couples need to use ART to conceive, it is vitally important that we find out as much as we can about what is causing malformations in these children, not only so that we can try to counteract the problem but also in order for health services to be able to plan for their future needs.”

The scientists are now trying to find out the origin of parental infertility for each child born after ART who has been affected by major malformation or epigenetic disorders.  “With this knowledge, we can better establish the origin of the malformation and whether it is more likely to be related to parental infertility or the ART procedure itself”, said Dr. Viot.  “We already know that imprinting disorders - where the mechanism in which gene expression depends on parental origin - are clearly more frequent in our cohort than in the general population.”

Imprinting disorders are all acquired because of either a maternal or paternal deletion on a chromosome, through inheritance of both chromosomes of a pair from only one parent, through mutations in some imprinted genes, or because of loss or gain of methylation (a process which is normally removed during zygote formation and re-established through successive cell divisions during development.  “The prevalence of the imprinting disorder Beckwith Wiedemann syndrome in our cohort is six times higher than we would expect in the general population, and for retinoblastoma the prevalence among ART children is 4.5 higher than in the general population”, said Dr. Viot.

“These results could be due to the effect of a number of different mechanisms. They could be due to the infertility itself, the ovarian stimulation for supernumerary oocyte production, the in vitro maturation of oocytes, the use of ICSI (direct injection of sperm), the culture media, the cryopreservation of gametes and embryos - we just don't know at present.  Finding this out will be a major step towards improving the health of children born after ART.”

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Doctors should tell couples about ART risks

Should the results of individual genetic studies be disclosed to participants?  Study queries the right to information in every case

Gothenburg, Sweden: Individual results of genetic research studies should not be disclosed to participants without careful consideration, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday).  Dr. Robin Hayeems, from the Department of Health Policy, Management and Evaluation at the University of Toronto, Canada, will say that she believes that the view held by many ethicists that individual genetic research findings should always be reported to participants involved in genetic research studies was perhaps misguided, and that to do so without careful consideration of evidentiary assumptions and clinical capacity could distort the responsibilities of researchers and lead to misunderstanding.

Dr. Hayeems leads the GE3LS (Genomics and its Ethical, Economic, Environmental, Legal and Social Aspects) component of a Genome Canada funded basic science project that is looking at identifying the genes that can modify the severity or clinical effects of cystic fibrosis (CF).   Together with the study co-lead Professor Fiona Miller, in charge of the GE3LS component of the Genome Canada funded autism genome project, her team surveyed researchers from around the world who were involved in genetics research related to CF and autism.   “We were interested in their perspectives about sharing genetic research results with individual study participants in order to be able to add their voices to the ongoing debate about whether and under what circumstances researchers are under an obligation to report these results to research participants”, she said.

The survey found that 80% of the researchers agreed that individuals in whom a genetic variation had been identified should be informed of this finding if it were judged to be clinically significant.   Yet it also revealed considerable variation among researchers in deciding when a result was clinically significant. Researchers felt less confident about the clinical significance of a result when the finding was related to autism research, was less scientifically robust, and was incidental to the condition being studied.  Further, researchers were 40% less likely to report it when they were unable to provide participants with the requisite medical advice related to the finding.  There were also differences between scientific disciplines, with clinical researchers being 1.8 times more likely to class a particular finding as clinically significant and 1.5 times more likely to report it to study participants than were molecular and statistical researchers.

“Our understanding of how genetic factors contribute to the heterogeneous collection of conditions that comprise the autism spectrum disorders is in its infancy.   By contrast, though much remains to be learned about the genetics of CF, the clinical consequences of classical CF and the basic genetic defect that causes it has been known for some time”, said Dr. Hayeems.  

“I think our discovery that an autism-relevant finding engenders less confidence with respect to clinical significance compared to a CF-relevant finding reflects researchers' implicit sense of the fundamental uncertainty that still prevails with respect to the genetics of autism.   What is interesting about the survey design is that we can say overall that confidence in an autism-related genetic finding was lacking compared to a CF-related finding, even when the autism-related finding they were asked to judge was, by design, quite robust.

 “Most, but not all, ethicists endorse an obligation to report genetic research results about individuals because they consider it to be clinically relevant information that individuals have a right to receive.  This argument presumes that these research results constitute such information, and that the judgment of clinical significance is relatively straightforward.  Our work suggests that this presumption may be misplaced. The results of the survey identify a set of factors that appear to influence researchers as they consider whether a result is clinically significant and whether it should indeed be reported. These factors go beyond scientific standards of robustness to include underlying uncertainties about the role of genetics in certain conditions, as well as researcher training and research team capacity”, she said.

The GE3LS team now intends to encourage institutional research bodies and the wider research ethics community to revisit their thinking about the obligation to report research results to include a broader set of factors so that the complexity of the issue is fully reflected.  “Our work highlights an important intersection between health research and health care”, said Professor Miller.  “This intersection raises important questions.  Are results being interpreted and reported in the context of a research relationship in which the norms of clinical care cannot be expected or, in the context of clinical care, in which case these norms are assumed?  What context is assumed, and who is responsible - researchers, or health care systems - for ensuring appropriate disclosure and follow up?” she concluded.

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