In the news

  • Newsletter Edition
The PHG Foundation monthly newsletter features news and views about genetics and genetics research, from a public health perspective. The newsletter is written by staff of the PHG Foundation.

In the news

News story   |   By Dr Philippa Brice   |   Published 27 July 2010

In a new review of health-related ‘arms-length bodies’ or ALBs, UK Health Secretary Andrew Lansley has announced that several major health agencies are to be scrapped in an attempt to save money and reduce bureaucracy (see press release). The affected bodies include the Human Fertilisation and Embryology Authority (HFEA), the Human Tissue Authority (HTA) and the Health Protection Agency (HPA).


It is not yet clear how all the functions currently served by these agencies will be fulfilled. A new research regulatory body is apparently to be established, incorporating some functions of the HFEA; other HFEA activities will be transferred to the Care Quality Commission, and the Health and Social Care Information Centre in the next few years. The HPA’s functions will fall within a new Public Health Service, whilst the HTA’s activities in licensing uses of human tissue will be divided between the MHRA and the Care Quality Commission.


With respect to the proposed new research regulatory body, functions are said to be subject to the outcome of the current Academy of Medical Sciences (AMS) review of medical and science research regulation (see previous news), but there is suggested to be a ‘significant advantage’ in consolidating related research regulation currently overseen by the HTA, HFEA and the research and ethics functions of the National Patient Safety Agency, which is also to be disbanded. Patient safety oversight will rest with the National Commissioning Board.

The Government review states that new and consolidated ALBs will, where appropriate, ‘be expected to exploit commercial opportunities and maximise commercial discipline across the sector’. This charge could potentially be at odds with the normal function of research ethics and regulation, which is typically to protect the interests and sensibilities of patients and the wider public where they may be at odds with the scientific research aims or practices; Maximizing commercial opportunities could conflict directly with this, so it will be important for the priorities and responsibilities of a new regulator to be very clearly delineated to maintain public trust, whilst supporting scientific and medical research. 

News story   |   By Dr Caroline Wright   |   Published 26 July 2010

It has been another tumultuous few weeks for the world of consumer genetics. Following recent their announcement that the US Food and Drug Administration (FDA) would seek to regulate direct-to-consumer (DTC) genetic testing services as medical devices, communicated through a series of letters to the most prominent DTC genomics companies (see previous news), it has now sent a further 14 device notification letters out to a select but growing group of genetic test providers (see Genomics Law Report). The move occurred during the FDA’s widely publicised meeting on the regulation of laboratory-developed-tests (LDTs, see previous news), during which the matter of DTC tests was extensively discussed.

Meanwhile, the US House of Representatives Committee on Energy and Commerce conducted their own hearing on “Direct-To-Consumer Genetic Testing and the Consequences to Public Health” (see Genomics Law Report for full analysis). As well as receiving briefings from various experts, including representatives of three of the major US DTC companies (23andme, Navigenics and Pathway Genomics), the Committee was also presented with a recent report on DTC genetic testing from the Government Accountability Office (GAO).


Comment: The conclusions from these meetings are currently unknown and the outcome is difficult to predict either within the US or internationally. The GAO’s Report of it’s undercover investigation of DTC genomics companies is undoubtedly damaging, but is also overly alarmist and gives no indication of how widespread the bad practice might be in this versus any other industry. While there is general agreement that some level of regulation is required in this fledgling industry - to ensure that the genotyping is accurate and that consumers are not misled by extravagant and unfounded health claims - it is unclear what form that regulation should take. As clinical geneticist Dr Jim Evans points out in his testimony to Congress, “The gap between claims and reality should be closed. It doesn’t even require new regulations, just enforcement of existing standards that are, at least in part, promulgated and promoted by the Federal Trade Commission”.


In the continuing absence of any evidence of harm caused by these tests, and the likely increasing availability of whole genome sequencing and open source analysis software, regulators should avoid creating restrictive legislation or exhibiting unnecessary genetic exceptionalism. Although there is similarly scant evidence of utility of personal genomics, this is not (and should not) be a requirement for a product simply to be available for a consumer to choose to purchase. We believe that it is inappropriate to use existing medical device legislation to regulate DTC genomics services (which are neither simple devices nor used for medical purposes) and they may also fall outside attempts to regulate all LDTs as the genotyping assays are frequently performed at contracted laboratories. Instead, the PHG Foundation advocates a fairly liberal approach to regulation of DTC genetic testing services, in which transparency of information is paramount, and have previously identified five specific points where formal regulation would be welcome:

  • INFORMATION: Appropriate information and a proportionate set of consent procedures should be in place prior to testing, such that the citizen is unambiguously informed about the nature of what he or she will receive by way of information and its possible implications
  • ANALYTICAL VALIDITY: Laboratories providing an assay service should undergo accreditation procedures and subject themselves to stringent QA requirements (e.g. CLIA certification in the US), so that citizens themselves can have confidence in the genotypes that are generated
  • SCIENTIFIC VALIDITY: Statutory regulations should be put in place to ensure that the scientific validity of the clinical claim is established, i.e. the link between the disorder and the genetic variant is established as a true and real relationship
  • ACCESS TO ADVICE: All providers should ensure that consumers have access to named and appropriately qualified professionals with the necessary competence to interpret the assay measurement and provide advice and support to consumers regarding the interpretation of the test result to consumers
  • CLAIMS: Guidelines and consumer protection regulations should either be strengthened to prevent misleading claims for the product or service, including unsubstantiated and overhyped assertions concerning clinical utility, or action should be taken to ensure that existing regulatory powers are enforced

  • News story   |   By Dr Philippa Brice   |   Published 15 July 2010

    The Office of Population Health Genomics of the West Australian Department of Health has this week released new Guidelines for human biobanks, genetic research databases and associated data. The Guidelines are intended for biobanks, human and population genetic research databases within the jurisdiction of the WA Department of Health, of which there are around 100, but may also be useful for other facilities and research ethics committees. They were built on the OECD recommended draft Guidelines for Human Biobanks and Genetic Research Databases (see previous news), with input from a range of local stakeholders and wider public consultation.


    The Guidelines cover general principles and recommended best practices for the establishment, governance, management, oversight and (if required) eventual closure of biobanking facilities. This includes consideration of access to and protection of samples and data, including privacy, benefit-sharing and intellectual property issues.

    Director of the Office of Population Health Genomics Dr Peter O'Leary said that the guidelines would ‘strengthen WA’s position as an innovative leader in genetic research and data linkage’ (see press release). 

    News story   |   By Dr Philippa Brice   |   Published 14 July 2010

    A major new study funded by Parkinson's UK will use induced pluripotent stem (IPS) cells to investigate Parkinson's disease. Parkinson’s is a progressive neurological disorder that affects motor functions, causing slowing of certain movements, postural instability and tremor (involuntary shaking). It affects around 120,000 people in the UK and is the second most common neurodegenerative disease (see BBC news).


    IPS cells are stem cells with the potential to develop into different sorts of cells that have been derived from adult cells – in this case, skin cells from more than1,000 patients with early stage Parkinson's, which will be used to recreate neurons (nerve cells) of they type affected by the disease. It is very difficult to obtain diseased nerve cells directly from patients, as samples of brain tissue are not easily removed in the way that some other tissues may be biopsied.


    The neurons will be produced by the Oxford Parkinson's Disease Centre and used for a range of investigations, including comparison with healthy neurons and testing of potential drugs. Details of the project were described at the UK National Stem Cell Network annual science meeting this week.

    A small proportion of Parkinson's disease patients have a rare, inherited form of the disease; the majority of cases are sporadic, having a complex (and as yet poorly understood) basis involving a range of interacting genetic and environmental causes. A large scale study into the genetics of Parkinson's disease is being run by genetic testing company 23andme (see previous news) with financial backing from both Google and its co-founder Sergey Brin, who has a family history of the disease and has reportedly invested around US$10 / £6 million of his own in addition to some US$6 / £4 million from the search engine company (see Telegraph article). 

    News story   |   By Dr Caroline Wright   |   Published 14 July 2010

    A new online community resource for personal genomics called Genomes Unzipped (GNZ) has been launched this week. The website is a collaborative venture between a group of researchers and genomics bloggers, including individuals from Genetic Future, Genomics Law Report and Genetic Inference, as well as the PHG Foundation.


    With a range of experience in the group, the aim of GNZ is to provide the basic knowledge and tools that individuals interested in personal genomics need to explore their own genetic information in a responsible, informed manner. GNZ will feature technical analyses of personal genomics developments and services, including detailed analysis of the scientific basis of tests offered direct-to-consumer by personal genomics companies. It will also include dissections of important new papers in the field and discussion of the ethical, legal and social issues presented by new developments in this rapidly evolving field.

    News story   |   By Dr Philippa Brice   |   Published 11 July 2010

    A report from the European Science Foundation (ESF) released last month examines key issues in human stem cell research and regenerative medicine, which it hails as having the promise to be ‘one of the most fascinating and controversial scientific developments of the 21st century’ (see press release). Regulation of stem cell research varies widely between different European countries: some prohibit human embryonic stem (HES) cell research; seven permit the production of human stem cells from spare in vitro fertilisation (IVF) embryos; three (the UK, Belgium and Sweden) allow the creation of embryos purely for research, albeit under strict regulation; and six have no legislative policies at all.

    The report highlights the complex situation for patenting HES cell technologies in Europe due to reported ambiguities in ethical guidelines within the European Patent Convention. For example, whether therapeutic applications of stem cells would be considered commercial; and whether inventions involving the destruction of a human embryo at the early blastocyst stage of development are prohibited as those involving the destruction of older embryos are.


    Another key major assertion of the report is that HES cell lines may not receive as much funding or scientific scrutiny as those derived from adult pluripotent stem cells, since the latter are easier to produce and do not involve ethical objections to the use of human embryos. The report calls for increased and equitable national and EU funding for human embryonic stem cell research, noting that the two types of cells are not identical and that HES cells may offer safety benefits if used for therapeutic applications.


    Interestingly, the opposing issue has arisen in the US, where the Court of Appeals in Washington DC has granted permission for two adult stem cell researchers to file a lawsuit against the National Institutes of Health on the basis that the new Federal government support for embryonic stem cell research (see previous news) is diverting funding away from their own parallel – and some would argue, ethically superior - field of research [Nature (2010) 466: 159; doi:10.1038/466159a].


    The ESF report is spot on with the assessment that this field is fascinating and controversial; whether more countries will move towards common ground on this issue, or adopt increasingly polarised approaches is interesting to contemplate. In purely scientific terms, it is certainly more appropriate to pursue both lines of research simultaneously – but what will the majority view be in terms of ethical acceptability?

    News story   |   By Dr Philippa Brice   |   Published 8 July 2010

    The UK Biobank has announced that it has exceeded the original recruitment target of 500,000 individuals aged 40-69. However, in many senses the work is just beginning as the project follows participants over time to follow their health outcomes and attempt to correlate this with genetic, clinical and environmental data already held. Chief scientist Dr Tim Sprosen it could be another decade or more before major research findings began to emerge, commenting: "In 10 or 20 years time, we will be able to analyse things in the samples that researchers haven't even thought about yet…We are custodians of this resource. The next generation of scientists, who might still be in primary school today, will use new tests and be able to unlock new secrets as to how we prevent disease" (see BBC news).


    Meanwhile, plans for a German biobank are proceeding; the German National Cohort will be smaller than the UK version, seeking to recruit 200,000 participants, but in addition to including a wider age range (healthy adults between 20 and 69), the project will also involve more detailed clinical analysis, to include repeat medical examinations after five years and magnetic resonance imaging (MRI) scanning of the major organs of 40,000 participants to look for early signs of disease. Feasibility and pilot studies are reportedly to be funded by the Helmholtz Association, whilst German governmental agencies are being asked to fund the main part of the initiative (see Financial Times article).


    Europe is currently enjoying rapid growth in both the number of national biobanks and efforts to build co-operative networks between biobanks, such as via the European Biobanking and Biomolecular Resources Research Infrastructure or EuroBiobank (see previous news). However, there are also concerns about the difficulty in securing appropriate, reliable funding for such long-term projects (see Science Business blog).

    A planned new facility at the Karolinska Institutet in Sweden hopes to create the world’s largest biobank by creating a national infrastructure to join individual Swedish biobank projects (see Swedish Research Council). 

    News story   |   By Dr Philippa Brice   |   Published 5 July 2010

    A new genetic technique to screen embryos produced by in vitro fertilisation (IVF) has been hailed as a potential advance. The test, called 24sure, analyses chromosome number using then polar body from the fertilised egg cell (ooctye); abnormal numbers of chromosomes (aneuploidy) is thought to be a leading cause of early miscarriage. This is a significant problem for IVF, especially as aneuploidy rates are higher in older women. The less severe forms of aneuploidy may not result in pregnancy loss, but nevertheless cause significant fetal abnormality.


    A small scale study by the European Society of Human Reproduction and Embryology (ESHRE) preimplantation genetic screening (PGS) task force found the test could identify aneuploidy (abnormal chromosome number) in 89% of fertilised eggs within 12 hours, fast enough to make normal implantation feasible (see press release).


    PGS Task Force coordinator Professor Geraedts commented: “With chromosome errors being the predominant cause of non-viability of the embryo, we hope this approach will in future effectively improve results in assisted reproduction”. However, there is not yet any evidence to show that such testing actually does improve pregnancy and birth rates among IVF patients, with more trials required (see BBC news).

    This form of pre-implantation chromosomal analysis should not be confused with preimplantation genetic diagnosis (testing of embryos to determine whether they will be affected by a specific serious genetic disorder, typically due to family history of that disease), nor with Counsyl’s ‘universal’ preconceptual genetic test, which screens prospective parents to see whether are carriers for a large number of different genetic disorders of varying severity (see previous news). 

    News story   |   By Dr Philippa Brice   |   Published 3 July 2010

    Kits to take saliva samples at home and send samples for DNA analysis, already used for selected commercial applications such as paternity testing and genetic disease risk prediction, is being put to new use. A UK charity, the Anthony Nolan Trust, has launched a new system to recruit members of the public to the donor stem cell register using saliva samples (see BBC news).


    Previously, registering as a potential stem cell donor necessitated a blood sample taken by a healthcare professional. The charity hopes to boost recruitment with this new and more convenient approach; donors will need to send the saliva sample along with a completed medical questionnaire. Their DNA samples will be analysed to determine basic tissue type. Should a possible match between a registered donor and a patient recipient arise, the donor will be contacted for further tests; if the donor agrees and is compatible with the patient, blood stem cells or bone marrow can be taken and used to treat leukaemia or other blood disorders in the recipient.

    Chief executive Henny Braund said, “We urgently need to increase the number of people on our register, and saliva testing will help us do that much more quickly and effectively” (see press release). It is also hoped that the kits will facilitate testing of family members to identify tissues matches for people who need transplants. 

    Research articles

    Research article   |   By Dr Sowmiya Moorthie   |   Published 30 July 2010

    Sudden cardiac death (SCD) can arise through multiple different molecular mechanisms, and enormous progress has recently been made in understanding genetics factors that increase SCD risk in those with inherited cardiovascular disease (see the PHG Foundation Heart to Heart Report). However, the identification of genetic factors that may determine individuals who are susceptible to SCD in the general population has been limited. As SCD may be the first clinical expression of heart disease in some of these individuals, a greater understanding of the genetic and molecular factors involved may help earlier identification and treatment.

    One possible mechanisms of SCD is when a myocardial infarction (MI) leads to ventricular fibrillation (uncoordinated contraction of ventricles). However, not all individuals who have an MI go onto to develop ventricular fibrillation. In order to identify factors that may underlie this difference, Bezzina et al. analysed the genes of 972 individuals with a first acute MI from the Arrhythmia Genetics in The Netherlands (AGNES) study [Bezzina et al. (2010) Nat. Genet. 42(8):688-91]. Of these, 515 individuals had experienced ventricular fibrillation and 457 had not.

    The genome-wide association study revealed a SNP (rs2824292) near chromosome 21q21 that reached genome-wide significance associated with ventricular fibrillation. The frequency of this SNP containing the minor allele was found in 53% of cases and 39% of controls, with an odds ratio of 1.78 (95% CI 1.47-2.13). This association was replicated in an independent MI case-control set from the Amsterdam Resuscitation Study- Myocardial Infarction (ARREST-MI) study, consisting of 146 out-of hospital individuals with MI complicated by ventricular fibrillation and 391 individuals who had survived an MI.

    The gene closest to this SNP is CXADR, which encodes a viral receptor that has been implicated in pathogenesis of viral myocarditis. The authors suggest that this is a novel candidate gene for arrhythmia susceptibility, and are aiming to conduct further studies into the influence of the genotype at rs2824292 on its expression.


    Research article   |   By Dr Philippa Brice   |   Published 29 July 2010

    Fragile X syndrome is the most common inherited form of learning disability. Caused by expansion of a section of the X-chromosome, it affects around one in 3,600 men (see BBC Health); women are less frequently affected and may have milder symptoms. Pre-mutation carriers with smaller expansion regions may not show symptoms but can develop related health problems later in life and may have children affected by Fragile X.

    Population screening for Fragile X has been considered in different countries for some years now (see previous news), but raises distinct issues compared with other inherited disorders, due to the variable risks to pre-mutation carriers and female mutation carriers; the latter show very variable clinical features ranging from unaffected to severe learning disability.


    A newsystematic review has examined published evidence relating to population-based screening for fragile X in women of reproductive age (ten studies) and newborn babies (one study) between 1991 and 2009 [Hill MK et al. (2010) Genet Med. 2010 Jul;12(7):396-410]. This review included analysis of papers examining psychosocial elements of screening: two forming part of the screening studies, and nine additional articles.


    The authors found a general lack of evidence; although published research showed population screening to be largely effective, all the studies were observational, as opposed to controlled (comparing screening with alternative screening or no screening). Uptake of testing was found to range from 7.9% to 92% in different prenatal screening studies, 79% for the newborn study. Women premutation carriers identified by screening largely took up the offer of fetal testing, with a variable proportion opting to terminate affected pregnancies.


    The challenges of providing effective genetic counselling to affected women and families who knew little or nothing about fragile X syndrome were noted; although he condition is common, it is not well recognised in the general population in the way that some other genetic disorders such as cystic fibrosis are. The main conclusions were that controlled studies should be conducted to examine both the technical and psychosocial elements of screening for Fragile X, and that specialised guidance for genetic counselling would be required.


    Newborn screening was found to have more limitations than adult carrier screening. As reiterated in an accompanying commentary, although prompt identification of full mutation carriers can allow improved care, it cannot predict which female carriers will show clinical symptoms, and also identifies premutation carriers at risk of adult-onset conditions and other forms of X-chromosomal abnormality [Coffee B. Genet Med. 2010 Jul;12(7):411-2 ].


    In addition to improved education and counselling, the timing of screening would appear to be crucial, with preconception screening preferable to prenatal screening among adult women, and the suggestion that optional infant screening would be a better option than newborn screening.

    Research article   |   By Dr Philippa Brice   |   Published 26 July 2010

    Gene therapy is the delivery of genetic material to correct a genetic defect associated with severe disease, replacing a non-functional gene with a functional version or inactivating a malfunctioning gene. It is in a sense the ‘holy grail’ of genetic medicine, offering the potential of a genuine cure for serious inherited diseases, and potentially also more common conditions such as cancer. However, it is difficult to achieve long-term therapeutic effects, and there is a risk of cancers caused by inappropriate insertion of the gene therapy vector in the cellular genome of the patient.

    One of the earliest gene therapy successes was for the X-linked form of severe combined immunodeficiency (SCID-X1); this is a rare disease where a mutation prevents the formation of a functional immune system. Affected children, if untreated, die very young from infections. Gene therapy trials produced very positive results (see previous news), but were dogged by cases of therapy-associated leukaemia (see previous news).


    A new paper in the New England Journal of Medicine revisits nine children who received gene therapy for SCID-X1 in infancy, 8-11 years on. The therapy produced long-term results in eight of the nine children, allowing them to live normally and produce broadly normal immune responses to common infections [Hacein-Bey-Abina S et al. (2010) N Engl J Med; 363:355-364].


    However, their immune systems were not perfect, being better able to generate T-cells than NK-cells, and some (but not all) needed additional therapy to provide antibodies, another crucial element of the immune system. More seriously, a total of four of the nine boys developed leukemia; they received chemotherapy, but one died. In the three survivors, normal immune functions returned once chemotherapy ended.


    Comment: Gene therapy was not completely effective in one of the nine boys, and caused leukaemia in four others, in one case fatal. However, it is important to note that without treatment, all of these boys would have died much earlier. Even where tissue-matched bone marrow transplants (the only alternative treatment) are available, survival rates are reportedly only around 70%.


    Clearly, gene therapy is a long way from being suitable for moderate conditions, or those where alternative treatments are possible, but for these most serious diseases, it can work. The ongoing challenge is to maximise efficacy whilst minimising the associated risks.

    Research article   |   By Dr Sowmiya Moorthie   |   Published 22 July 2010

    Beta thalassaemia is one of the most common autosomal recessive disorders worldwide and mainly affects individuals from Mediterranean, Middle Eastern and Asian populations. It is caused by mutations in the haemoglobin beta gene leading to either a reduction in β-globin production or the absence of β-globin synthesis, and consequently abnormal haemoglobin molecules. Individuals with a severe form of this disorder - β-thalassaemia major, suffer from life threatening anaemia and require regular blood transfusions and chelation therapy to prevent iron overload. Bone marrow transplantation is also an option for treatment, but its success is dependent on the availability of compatible donor cells and the condition of the patient.

    A recent study published in EMBO Molecular Medicine describes a pre-clinical trial in which gene transfer has been used to correct for the deficiency in β-globin in cells from patients with the disease [Roselli et al. (2010) EMBO Mol. Med. doi: 10.1002/emmm.201000083]. The researchers had previously developed a viral vector called GLOBE which contained the β-globin gene and could be transferred into haematopoietic stem cells (HSC), which give rise to different types of blood cells. They also showed that this resulted in the production of β–globin, and the transfer of these cells can correct β-thalassaemia in mouse models of the disease.

    Prior to clinical trials in humans, the researchers wanted to ensure that this method of therapy was efficient and safe. In order to do this, they obtained bone marrow stem cells from 44 patients with β-thalassaemia major and analysed the properties of particular cells (progenitor HSC and CD34 cells) before and after transfer of the GLOBE vector. Properties such as frequency and site of integration of the gene were analysed, as well as its impact on the production of haemoglobin and the subsequent development of the cell.

    Extensive analysis indicated that the vector was able to successfully be transferred into these cells and integrated into transcriptionally active regions, without bias for cancer-related genes. Inappropriate activation of such oncogenes by gene therapy vectors, causing cancer, has occurred before in such trials (see previous news).Integration of the vector restored synthesis of haemoglobin and did not appear to affect the subsequent development or the number of cells.

    Comment: These pre-clinical trials are an initial step in the development of gene therapy for this disease, and may also provide a model for the use of gene therapy to treat other diseases such as sickle cell disease, for which the need to develop an effective therapy is pressing [Orkin and Higgs (2010) Science 329 (5989):291-292].

    Research article   |   By Dr Susmita Chowdhury   |   Published 21 July 2010

    Pancreatic cancer is the 11th commonest cancer in the UK, with around 7,800 new diagnosed cases each year (see CRUK CancerStats). Risk factors include age, family history, mutations in the BRCA2 gene, smoking, fatty and sugary diet, obesity and lack of physical activity. It is one of the least treatable cancers, with a 5-year survival rate of around 3%, and its poor diagnosis is primarily attributable to late detection. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) currently offers screening to individuals with an inherited predisposition to pancreatic cancer, based on imaging and blood tests.


    Though active investigational screening protocols show positive outcomes for pancreatic cancer screening in high risk groups, the impact of pancreatic cancer screening on well-being is unknown. A new study has now been published investigating whether individuals participating in a pancreatic cancer screening programme experience disruptions in risk perception, cancer-related anxiety or emotional distress [Maheu et al. (2010) Fam Cancer doi:10.1007/s10689-010-9354-5].


    This prospective study included 131 participants with a history of familial pancreatic cancer (FPC) and another 67 participants who were BRCA2 carriers; BRCA2 carriers were told that they had an estimated 5% lifetime risk of developing pancreatic cancer, while the FPC group was informed that they are expected to have a ‘higher’ risk than normal. Genetic counselling was provided prior to testing, in addition to information about the disease and the risks and benefits of screening. All participants were assessed at baseline and at 3 months following screening for levels of risk perception, anxiety related to pancreatic cancer and general distress.


    The authors concluded that participation in a pancreatic cancer screening programme did not lead to a significant increase in risk perception, cancer worry or general distress, and that those with high baseline levels of risk perception and distress may benefit from comprehensive risk assessment and support.


    Comment: This study helps to give further insight to the question of whether genetic susceptibility testing of healthy individuals causes psychological and emotional distress (see previous news). Although the authors conclude that it does not, the generalisabilty of this conclusion is questionable. The study was relatively small and lacked normal (low risk) controls, and most of the participants were affluent, well-educated Caucasian females who were actively seeking participation in a pancreatic cancer screening protocol. Additionally, the level of detailed information conveyed to the participants might not be feasible in a larger population screening programme. However, the results add to the small but gradually increasing body of literature suggesting that genetic susceptibility testing and risk prediction is minimally harmful.

    Research article   |   By Dr Caroline Wright   |   Published 19 July 2010

    Vitamin D deficiency affects more than a billion people worldwide, and causes rickets, accelerated age-related bone loss, and may also contribute to numerous common diseases including diabetes, cancer and cardiovascular disease. Although social, cultural and environmental factors are known affect vitamin D status – most notably, exposure to sunlight and dietary supplementation – twin studies suggest that genetic factors are also important, with heritability estimates of around 50%.

    An international, multicentre consortium has now published the findings of a large genome-wide association study (GWAS) involving nearly 34,000 individuals from 15 cohorts of European descent, which aimed to find common genetic variants affecting vitamin D concentration and risk of insufficiency [Wang TJ et al. Lancet (2010 376: 180-7]. In addition to genotyping genome-wide common variants and a small selection of candidate genes, the concentration of circulating 25-hydroxyvitamin D and vitamin D binding protein were measured and analysed along with age, sex, season and body-mass index. Common variants (SNPs) at three genetic loci reached the genome-wide significance threshold, all located near genes involved in vitamin D transport and metabolism. After correcting for other factors, these variants were also found to increase the risk of vitamin D insufficiency.

    Comment: As an accompanying news article highlights, the study is published against a backdrop of continuing international debate over public health policy regarding exposure to sunlight, in order to balance risk of skin cancer against that of vitamin D deficiency [Lancet (2010) 376:142]. This study is unlikely to have an impact on that debate; while the GWAS is notable for its large study size and attention to technical detail, the usefulness of the findings are currently unclear. Further work is needed to understand whether this genetic predisposition modifies the response to sun exposure or dietary intake of vitamin D, and how it affects response to treatment. Nonetheless, these findings will improve our biological understanding of how the body processes vitamin D - for example, as the accompanying Editorial points out, it is somewhat surprising that none of the genes identified are linked with skin pigmentation, which is known to be a major factor in vitamin D status [Bouillon R, Lancet (2010) 376:148-9]. Ultimately, this new molecular level of biological understanding could lead to improved treatments. 

    Research article   |   By Dr Philippa Brice   |   Published 7 July 2010

    Mutations in the BRCA1 and BRCA2 genes cause hereditary breast-ovarian cancer syndrome, with a greatly increased risk of certain cancers (particularly breast cancer) in affected individuals. What is less commonly understood is that men who inherit mutations in these genes may also develop breast cancer, albeit to a lesser degree than female mutation carriers. Male breast cancer is much rarer than in women, but inherited mutations, particularly in the BRCA2 gene, are a significant cause.

    A new paper in the Journal of Medical Genetics reports findings from a study of more than 300 families from parts of the UK with BRCA2 mutations to determine the risk of breast cancer in male BRCA2 carriers.


    Over 900 men were identified as first degree relatives of known BRCA2 mutation carriers. The researchers identified previous cases of breast cancer among these men, and followed them over time to identify new cases. They calculated that breast cancer risk among such men was 7.1% by age 70 years and 8.4% by age 80 years, concluding that awareness of breast cancer (to boost early diagnosis) in men was important for affected families [Evans DGR et al. (2010)J Med Genet doi:10.1136/jmg.2009.075176].


    Comment: This study provides a useful estimate of the risk of breast cancer among male relatives of BRCA2 mutation carriers at 6-9%. This compares with a population risk of just 0.1% (see BBC news), underlining the importance of making risks known to men in affected families, as suggested by the authors. Although some assumptions are made in the calculations such as that all men from the study who developed breast cancer were necessarily mutation carriers, it is nevertheless the largest study of the kind to date.

    Research article   |   By Dr Caroline Wright   |   Published 2 July 2010

    The increasing availability of genetic tests available direct-to-consumer (DTC) has led to extensive international debate about the regulation of such services (see previous news). In particular, genomic profiles that offer individual risk prediction for a plethora of different common diseases have raised a number of ethical questions relating to the potential harms of giving this kind of probabilistic, and potentially misleading, information to individuals (see previous news) without formal genetic counselling or professional medical advice.

    These issues are further elaborated in a new paper in the Journal of Medical Ethics, specifically in relation to testing for genetic susceptibility to autism [Jordan BR & Tsai DFC, JME (2010) doi: 10.1136/jme.2009.031385]. Autism is an increasingly prevalent neurodevelopment disorder which manifests in childhood and is broadly characterised by impaired social interaction and repetitive behaviour. Although twin studies suggest that the disorder is highly heritable, genome-wide association studies for both SNPs (see previous news) and CNVs (see previous news) have thus far failed to explain much of the genetic basis of this multifactorial disease; diagnosis still involves numerous psychological tests combined with professional judgement, and risk prediction remains impossible. Nonetheless, a genetic susceptibility test is frequently conjectured in the media and is actively being developed commercially (though is not currently offered by any of the major DTC genomics companies).

    The authors question whether “a responsible test for autism could ever be commercially viable”, and suggest that this kind of genetic susceptibility test for multigenic diseases can only be useful if:

    (1)   the gene-disease association is robust (i.e. proven scientific validity);

    (2)   the relative risk conferred has a ‘significant’ clinical impact; and 

    (3)   there is an improved outcome as a result of testing (i.e. proven clinical utility).


    To date, none of these three criteria are adequately fulfilled for autism – or for many other common complex diseases. However, the authors argue that a putative autism genetic test is not like equivalent obesity or diabetes tests, because “a false positive result can be particularly damaging for early-age behavioural syndromes that are strongly influenced by the tone of parent-child interactions”.


    Comment: This thought-provoking article raises a number of interesting issues. Rather than arguing for genetic exceptionalism, whereby genetic information is given ‘special’ treatment (which is both practically and philosophically problematic), the authors are advocating a kind of ‘behavioural exceptionalism’, whereby DTC tests for specific psychological disorders should not be allowed. Laudable as this sentiment may appear, as with any kind of exceptionalism, it is difficult to see where to draw the line. Moreover, in practice, it will be increasingly difficult to achieve as we move towards an era in which genome profiling, or even whole genome sequencing, becomes more commonplace, and the internet abounds with genomic analysis services and open access bioinformatics software.


    There are also numerous issues relating to genetic testing of children, who are unable to give informed consent, and professional guidance generally recommends against testing except where there are immediate clinical benefits (see previous news). However, in the DTC setting, this could be difficult to achieve, and is potentially unnecessary for weakly predictive susceptibility tests. Before deciding what level of regulation is appropriate for these kinds of tests, evidence is needed that that the putative harms caused by testing really exist, and that they outweigh the potential benefits of allowing a free market approach.


    Finally, the list of three requirements for a genetic susceptibility test to be useful are certainly right, and should form the cornerstone of evidence-based medicine upon which publicly-funded national health services are based. But they are probably too stringent for a test to be available privately. Aside from regulating the analytical validity, through laboratory oversight and quality assurance, the best way to address the thorny issue of interpretation in consumer testing may be through transparency of information, to ensure consumers are not mislead by probabilistic test results. 

    New reviews and commentaries

    Selected new reviews and commentaries, 11 July 2010

    Reviews & commentaries : by Dr Philippa Brice

    The discovery of human genetic variations and their use as disease markers: past, present and future.

    Ku CS, Loy EY, Salim A, Pawitan Y, Chia KS. J Hum Genet. 2010 May 20. [Epub ahead of print]


    The Human Genome Project: 10 years later

    Lancet  375(9733): 2194.


    Patents in synthetic biology.

    Chan S, Sulston J. BMJ. 2010 Jun 14;340:c2984.


    A DNA education.

    Nature. 2010 Jun 17;465(7300):845-6. 


    Need for a wider view of autonomy in epidemiological research.

    Hansson MG. BMJ. 2010 May 5;340:c2335. doi: 10.1136/bmj.c2335


    Major heart disease genes prove elusive.

    Couzin-Frankel J. Science. 2010 Jun 4;328(5983):1220-1


    CISH and susceptibility to infectious diseases.

    Khor CC et al. N Engl J Med. 2010 Jun 3;362(22):2092-101. 


    Genes, the environment, and breast cancer.

    Narod SA. Lancet 375(9732): 2123-2124.


    Next-generation genomics: an integrative approach.

    Hawkins RD, Hon GC, Ren B. Nat Rev Genet. 2010 Jun 8;11(7):476-486. [Epub ahead of print]


    Another piece of the autism puzzle.

    State MW. Nat Genet. 2010 Jun;42(6):478-9.


    World view: Talking the talk

    Macilwain C. Nature. 2010 Jun 17;465(7300):867.


    Genomics and general practice: the next 10 years.

    Leung L. Aust Fam Physician. 2010 May;39(5):339-40.


    Likelihood ratios for genome medicine.

    Morgan AA, Chen R, Butte AJ. Genome Med. 2010 May 17;2(5):30. [Epub ahead of print]


    Coronary heart disease risk prediction in the era of genome-wide association studies: current status and what the future holds.

    Humphries SE, Drenos F, Ken-Dror G, Talmud PJ. Circulation. 2010 May 25;121(20):2235-48. 

    Family history: the neglected risk factor in disease prevention.

    Emery JD, Walter FM, Ravine D. Med J Aust. 2010 Jun 21;192(12):677-8.


    Genetics of Parkinson disease and essential tremor.

    Wider C, Ross OA, Wszolek ZK. Curr Opin Neurol. 2010 May 19. [Epub ahead of print]


    Genetic disorders of renal phosphate transport.

    Prié D, Friedlander G. N Engl J Med. 2010 Jun 24;362(25):2399-409.


    New approaches to population stratification in genome-wide association studies.

    Price AL, Zaitlen NA, Reich D, Patterson N. Nat Rev Genet. 2010 Jun 15;11(7):459-463. 

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