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 Susmita Chowdhury   |   Published 27 May 2010

Traditionally the Swedish government has spread its money to as many scientists as possible for research in the life sciences. The government has now decided to spend more than $75 million setting up a new building in Stockholm called the Science for Life Laboratory (SciLifeLab).


SciLifeLab Stockholm has been formed jointly by the Royal Institute of Technology (KTH), Karolinska Instituet (KI) and Stockholm University, creating one of Europe’s biggest genome centres, to house more than 200 researchers. This national resource centre,which will have an advanced technological infrastructure, will be dedicated to large scale bioscientific research with focus on biomedicine, including genome and proteome profiling, bioimaging and bioinformatics.


Though the SciLifeLab’s DNA sequencing output will be only 40% of that of the Wellcome Trust Sanger Institute in the UK, it will reportedly be unique in the degree to which it combines genomic and proteomic research, being also the only lab with antibodies to all human proteins and the ability to sequence human genomes. Multidisciplinary research will be carried out involving high throughput DNA sequencing, analysis of gene expression, protein profiling, cellular profiling, advanced bioinformatics, biostatistics and systems biology. These processes will enable comprehensive analyses of genes, transcripts, and proteins in humans and relevant microbes and to increase understanding of complex interplay between molecular component of living cells related to human diseases. Active collaboration and knowledge transfer is planned between academic researchers, the Swedish healthcare system, and the life science industry. 

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

 Delegates at the sixty-third World Health Assembly, a major international meeting between senior World Health Organization (WHO) officials and national Health Ministers held in Geneva last week, voted to adopt a range of resolutions relating to public health around the world. These included a resolution to address the problem of birth defects, especially in low- and middle-income countries, calling on Member States ‘to prevent birth defects wherever possible, to implement screening programmes, and to provide ongoing support and care to children with birth defects and their families’ (see press release).


The PHG Foundation is already engaged in a major project to tackle birth defects, also known as congenital anomalies or abnormalities – a wide range of conditions that are present from birth, ranging from genetic and chromosomal disorders through to physical malformations. The majority of birth defects are caused by genetic factors, though environmental factors can also cause or exacerbate them. The PHG Foundation has developed a special toolkit to help low and middle-income countries (where birth defects account for a significant proportion of child deaths and ongoing disability) assess their health needs and develop simple, effective services to prevent and care for this range of conditions. The toolkit is tpo be piloted in different international locations over the coming two years. The PHG Foundation is also working with external partners including the WHO on efforts to create and drive forward concerted global efforts to share expertise and resources in order to reduce the suffering associated with birth defects.

News story   |   By Dr Caroline Wright   |   Published 20 May 2010

Since the announcement last week that Pathway Genomics was intending to offer personal genome scans over-the-counter in the United States (US) (see previous news), the world of consumer genomics has been thrown into disarray. Until this announcement, regulatory bodies such as the US Food and Drug Administration (FDA) have done little more than keep a watchful eye on the area of direct-to-consumer (DTC) genetics tests. However, following the announcement that these tests might become available in high street stores, rather than just over the internet,  the FDA wasted no time in issuing a letter to the company the very next day asking for proof that the test had proper FDA approval or to explain why such approval is not necessary (see MSNBC news). A US official has since said that "selling a test over the counter without an FDA clearance, particularly for the type of claims they have, is not legal" (see the Economist). Within 48 hours of the original announcement, the retail stores involved reversed their decision to offer consumer genetic tests, pending a resolution by the FDA (see the Wall Street Journal).

The FDA has grappled with how to regulate the growing number of DTC genetic tests for several years, and it is still rather unclear how exactly these types of tests should be regulated (see the Genomics Law Report for an extensive summary of the current regulatory landscape). Nonetheless, at the end of a turbulent week, the US House of Representatives Committee on Energy and Commerce today launched an investigation into DTC genetic testing (see the official announcement). In a letter sent to three prominent American DTC companies (23andMe, Pathway Genomics and Navigenics) the Committee has requested information within the next few weeks on how individual risk of disease is determined and policies regarding the collection, storage, and processing of individual genetic samples.

Bizarrely, today’s announcement was accompanied by a rather contradictory revelation that students at University of California, Berkeley, will be offered free genome scans when they arrive (see New Scientist). This move is likely to draw both widespread excitement and condemnation in almost equal measures, due to the perceived usefulness of this information in future for individuals to improve their own health, and pertinent ethical concerns over data privacy and misinterpretation of the information (see coverage in the New York Times).

Comment: Given the lack of evidence of utility of these types of tests (see previous news), it seems a little premature to dismiss a number of very real concerns associated their increasing availability without good reason, and some level of regulation is certainly warranted. Before such tests can be offered legitimately with claims of improving health, evidence is needed that they are both scientifically valid and clinically useful.

That said, given the nature of the tests – most of which currently only analyse common variants and have very limited predictive power for individuals – regulators must be clear what ‘harm’ they are trying to prevent. Direct harms are unlikely to result from in vitro saliva-based tests, and the analytical accuracy of the genotyping assay itself is very high. Therefore, the possible indirect harms that could result from misinterpreting the information, such as psychological distress or false reassurance, are the main reason to regulate the tests. However, to date, there is very little evidence that these harms are actually occurring or causing a problem; moreover, regulating ‘interpretation’ is very difficult. Thus, there is a need to provide oversight of all DTC testing services, genetic or otherwise, to address these issues without taking an overly paternalistic approach that limits individual choice unnecessarily. Transparency of information, ensuring access to support from trained professionals, and preventing overhyped or misleading claims that are not backed up with robust evidence may be the best approach.

Perhaps the greatest harm of all is immeasurable – namely a possible loss of faith throughout society in the power of genetics. Once people realise that a genome scan is not a crystal ball, but a tool to investigate biology, there could be a backlash against the enormous worldwide investment in genomics research. Therefore companies, regulatory bodies, and professionals have a duty to diffuse the hype surrounding these tests and ensure that individuals are well informed enough to understand what they are buying.

News story   |   By Dr Philippa Brice   |   Published 18 May 2010

The potential role of genomics in medicine is changing rapidly as technological developments make quick, affordable genome sequencing increasingly feasible. Governments, health services, doctors, scientists and the wider public around the world are interested in how genomic medicine is likely to develop. In the UK, the House of Lords Science and Technology Committee led a consultation on this issue, resulting in the publication of the report Genomic Medicine in July 2009 (see previous news). This report looked at the implications of advances in genomics for UK health services. A subsequent Government response in December 2009 largely failed to engage with the urgency of recommendations in the original Report (see previous news), though it did make a commitment to establish a new cross-departmental Human Genomics Strategy Group (HGSG) charged with developing a strategic vision for genomics in the National Health Service (see GenomeWeb news).

Meanwhile, the PHG Foundation was leading an initiative to produce an independent expert response, in collaboration with the Centre for Science and Policy (CSaP) at the University of Cambridge. This new publication, Genomic Medicine: An Independent Response to the House of Lords Science and Technology Committee Report sets out the findings from a group of leading scientists, clinicians, policy makers and experts in ethics, law and social science, and their key recommendations for the strategic development and successful implementation of genomic medicine within the UK.


It finds that the original Government report overestimated the likely importance of genomics for the prediction and prevention of common complex diseases, whilst simultaneously failing to recommend action to realise the immediate potential of genomics to deliver improved diagnosis and care for individuals and families affected by single gene disorders and inherited subsets of complex disease, despite ample evidence of demonstrable health benefits.


In an attempt to redress the limitations of the original report and subsequent Government response, the new Report sets out twelve key recommendations for the prompt and effective development of genomic medicine within the NHS for the benefit of patient health. These include:

  • Urgently needed mechanisms for evaluating genetic tests and analyses
  • Creation and maintenance of new IT and informatics systems
  • Development of ethical codes for the storage, access and use of genomic tests and data
  • Investment in translational research
  • Public engagement

PHG Foundation Head of Science Caroline Wright commented: “We desperately need the equivalent of clinical trials for diagnostics. There’s an implicit assumption that testing is good, that knowledge is power, but the key question is does a test result helpfully change the management of a patient? If not, it is a waste of money. When public money is being spent, it must be spent sensibly to get better care outcomes. It’s really important that anything funded by health systems has evidence behind it” (see Times news report).


Launched today (see press release), the Independent Response will be presented to members of the HGSG later this month in advance of their inaugural meeting. Following on from this work, the PHG Foundation has initiated a major new programme to consider the implications of next generation high-throughput genome sequencing technologies for medicine and public health in greater detail, whilst the Centre for Science and Policy is launching a new Centre Interest Group on the $100 Genome, which will work in partnership with the PHG Foundation to bring together experts to explore the implications of low-cost full-genome sequencing in the near future.

News story   |   By Dr Sowmiya Moorthie   |   Published 17 May 2010

Technology assessment is a practice intended to enhance societal understanding of the implications of emerging scientific and technological developments, thereby ensuring their responsible implementation. Until 1995 the Office of Technology Assessment (OTA) provided US Congressional members and committees with objective and authoritative analysis of complex scientific and technical issues, and this model was widely copied around the world. Although there have been attempts to revive this agency, it has not been successful and alternatives have been proposed. Recently, the Woodrow Wilson International Center for Scholars has released a report defining the criteria for a new technology assessment model in the US (reported by Nature). 

The report, Reinventing Technology Assessment: A 21st Century Model, compares the congressional option, which mainly involves an expert panel, with an alternative model involving a wider group of stakeholders. It emphasises the importance of ‘participatory technology assessment’ (pTA), a practice employed in Europe to allow lay people to express their opinions and influence policy making. It proposes new national expert-and-participatory technology assessment institutional network (Expert & Citizen Assessment of Science & Technology (ECAST) network), which would be an independent network of government and non-partisan policy research institutions, universities and science museums across the United States. The authors state that although the ECAST model is more favourable at present, both models have their pros and cons and they “can potentially function sequentially or co-exist complementarily”. In addition, they emphasise that the time is now right to attempt new technology assessment practices.

Keywords : Public Involvementr

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

A US genetic testing company has announced that it is to sell kits in a national chain of pharmacies across the US from 14th May, with the exception of New York state where legal restrictions exist (see previous news). These types of shop already sell a range of over-the-counter testing kits, such as pregnancy and cholesterol tests. DNA-based paternity tests are reportedly already available over-the-counter in the US (see New York Times article).

Previous suggestion that over-the-counter genetic testing via high street shops is likely to become increasingly common is supported by this new move. The saliva collection kits will cost US$20-30, and include postage-paid envelope for sending to the provider for any or all of three types of genetic testing: drug responses, pre-pregnancy planning and ‘health conditions’ (see press release), for a cost of up to $249.

The health conditions test offers identification of genetic markers that indicate risk for adverse health conditions, including Type 1 & 2 Diabetes, breast cancer, obesity, Alzheimer's disease, prostate cancer and many more’, with the option to receive updates based on emerging science, although the website does note that ‘some markers have been researched more thoroughly than others’, a possible caveat that the actual health risk information provided by such testing can be highly limited. The pre-pregnancy planning test offers testing for carrier status for a range of rare inherited diseases, and is said to be suitable for people with a family history of genetic disorders or from ethnic groups at increased risk of specific diseases (for example, Tay Sachs disease among Ashkenazi Jews).

The inclusion of drug response testing in a direct-to-consumer kit is in line with recent recommendations (see previous news), although the number of drugs covered in this particular offering is limited, including predicted responses to warfarin (used to treat blood clots), tamoxifen (for selected breast cancers) and abacavir (for HIV infections).

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

The first, small-scale clinical trials of stem cells as a treatment for multiple sclerosis (MS) have reportedly shown promising results (see BBC news report). Six patients were injected with stem cells taken from their own bone marrow. Study leader Prof Neil Scolding of the University of Bristol said: "We didn't see patients throwing away their wheelchairs, throwing away their walking sticks” – but there were promising signs that the treatment increased nerve function and could have helped to stabilise the disease, preventing worsening of symptoms. The team hope to move on to larger clinical trials soon.


These results contrast markedly with news last month from the UK General Medical Council, which found Dutch doctor Robert Trossel guilty of exploiting vulnerable MS patients by sending them from his London practice to the Netherlands for unproven stem cell treatments. The GMC found that these were ‘unjustified by the scientific or clinical medical evidence’ and also that Trossel was not an expert either in neurology or stem cell therapeutics [Dyer C. BMJ. 2010 doi: 10.1136/bmj.c2009].


Comment: Unfortunately, premature, inappropriate (and in some cases, unscrupulous) application of novel biomedical treatments can result in disappointment and widespread scepticism about what may ultimately prove to be transformational new clinical tools. The balance between ethical research to develop and test innovations, and regulation to protect the public, is sometimes a delicate one. Here, however, both ends of the scale are shown in a good light - reporting of a promising trial without excessive claims of miracle cures or similar, and punitive action by a regulator against unprofessional behaviour.

Keywords : BioethicsHuman TissueStem Cellsruk

News story   |   By Dr Philippa Brice   |   Published 7 May 2010

A woman has filed a complaint with the US Equal Opportunity Commission and Connecticut Commission on Human Rights and Opportunities against her former employers, claiming genetic discrimination after losing her job following genetic testing. She was identified as a carrier of a mutation in the BRCA2 gene in 2004; her two sisters, who shared the same mutation, both had breast cancer. In 2009 the woman in question underwent preventative surgery to remove both breasts and reportedly told her employers MXenergy about the test and the surgery (see AP news).


Despite a good employment record over the previous three years, she claims that her MXenergy demoted her immediately following one absence for surgery, and made her redundant after the second. MXEnergy has not commented


This is the first publicised complaint involving genetic discrimination of this nature in the US. If the complaint is not resolved, the woman will be able to seek the right to sue her former employers under the Genetic Information Nondiscrimination Act (GINA), which came into force in 2009 (see previous news).

Research articles

Research article   |   By Dr Philippa Brice   |   Published 28 May 2010

The International Standard Cytogenomic Array (ISCA) Consortium has published a consensus statement in support of the use of chromosomal microarray (CMA) as a first line standard approach for the genetic evaluation of children with a range of disorders including developmental delay or intellectual disability (in the UK often termed learning disability), autism spectrum disorders, or multiple congenital anomalies (birth defects). These conditions account for a relatively large proportion of genetic testing as collectively they are relatively common.  CMA is a broad term encompassing ‘all types of array-based genomic copy number analyses, including array-based comparative genomic hybridization (aCGH)’.

The paper in the American Journal of Human Genetics presents the findings of a literature review of a total of 33 studies of CMA in nearly 22,000 people, comparing the technique with the current ‘gold-standard’ investigative approach of G-banded karyotyping [Miller DT et al. (2010) Am J Hum Genet. 86(5):749-64]. The study found that using microarray analysis increased diagnosis of chromosomal abnormalities underlying otherwise unexplained cases of learning disability, autism spectrum disorder or multiple congenital anomalies from around 3% for karyotyping to 15-20%. This is because the technique is able to detect small-scale (submicroscopic) chromosomal rearrangements that would not be visible from karyotyping, although the latter technique is better able to detect some rarer forms of abnormality (balanced rearrangements mosaicism than CMA.


The ISCA Consortium, which also held two international workshops on the subject as part of their investigation, concluded that CMA should therefore be used as a first-line approach for investigating such cases, although karyotyping should still be used for initial investigation of cases where there are strong medical reasons to suspect larger-scale chromosomal abnormalities – family history of chromosomal disorders or recurrent miscarriages (which often result from underlying chromosomal problems).


A second paper in the same journal reports a health economic analysis of the use of array genomic hybridization (aCGH or arrayCGH) compared with conventional karotyping for the detection of choromosmal causes of learning disability found that  despite the greater expense of aCGH, using the technique as a first line test was cost-effective, whereas using it only after karyotyping analysis was not [Regier DA, Friedman JM, Marra CA (2010). Am J Hum Genet. 86(5):765-72].

Comment: These conclusions are broadly in line with UK findings; the PHG Foundation originally worked with the UK Genetic Testing Network (UKGTN) to analyse the potential for using arrayCGH for the diagnosis of learning disability. The 2006 report, Evaluation of array-CGH for chromosomal abnormalities in clinical practice, was subsequently updated with systematic reviews of new evidence on this subject for the UKGTN; the latest review also suggested an increased diagnostic yield from the use of arrayCGH for patients with learning disability and congenital anomalies, but drew attention to the high rates of false positive diagnosis and the need for caution in clinical practice [Sagoo GS et al. (2009) Genet Med. 2009 Mar;11(3):139-46]. The ISCA is currently developing a public database of clinical CMA data over the nest two years to help develop clinical guidelines and software for interpretation of CMA tests (see Medical News Today).

Research article   |   By Dr Gurdeep Sagoo   |   Published 25 May 2010

Infectious diseases such as tuberculosis (TB), malaria, and invasive bacterial disease together account for more than 5 million deaths each year in the developing world, with one third of the world’s population currently infected with TB bacillus according to the World Health Organization (WHO). Although differences in disease susceptibility can be attributed in part to environmental factors such as malnutrition and poor hygiene as well as infection with human immunodeficiency virus (HIV), a large proportion of variation is still unexplained with studies suggesting that genetics also plays a role.


A new study published in The New England Journal of Medicine identifies genetic variants within a single gene as associated with increasing susceptibility to major infectious diseases [Khor et al. (2010) New Eng J Med 19 May; doi:10.1056/NEJMoa0905606]. The CISH gene encodes the cytokine-inducible SRC homology 2 domain protein, a regulator of cytokine signalling and a candidate gene for involvement in susceptibility to infectious diseases.


Khor et al. analysed susceptibility to TB, severe malaria or bacteraemia using case-control data from seven studies involving nearly 8,500 individuals from clinical sites in Kenya, the Gambia, Malawi, Hong Kong and Vietnam. Forty-eight individuals (24 cases and 24 controls) from the Kenyan Bacteraemia (KB) study had their CISH gene sequenced, identifying eight common SNPs. These SNPs were then genotyped in the remaining individuals from the KB study with four SNPs showing association (-639, -292, -163, 3415). Further genotyping in the other six case-control studies identified an additional SNP ( 1320). These five SNPs when pooled across all studies did not show any significant interaction but did show increased disease susceptibility relative to the number of risk alleles carried by an individual (0, 1, 2, 3, or ≥4) although one SNP (-292) accounted for most of the disease association observed.


A small gene expression study looking at three of these SNPs in a different population (healthy adult Han Chinese) indicated that one (-292) may affect expression of the CISH protein following stimulation with interleukin-2.


Comment: The authors identified five SNPs located within the CISH gene that show increased association with three major forms of infectious disease. Disease susceptibility also increased in relation to the number of risk alleles carried. The association with the -292 SNP, located in the promoter region, was also statistically significant in six of the seven individual contributing studies. This SNP was shown in a small number of individuals to reduce gene expression levels for a protein that is a member of the suppressor of cytokine signalling family. The inflammatory cytokine response is a key element of the host immune response to infection, and these results suggest that regulators of cytokine signalling, such as the CISH gene, may as postulated play an important role in resistance or susceptibility to several infectious diseases.

Research article   |   By Dr Philippa Brice   |   Published 24 May 2010

The human microbiome refers to the enormous collective community of different micro-organisms living in and on the human body, such as viruses, bacteria, and forms of fungi. The composition of the microbiome appears to vary between different individuals. The Human Microbiome Project was launched in 2008 (see previous news) in order to explore the function of these microbes in human health and disease, and one component of the project was attempts to produce reference genome sequences for at least 900 bacterial, viral and fungal species from different key sites within the human body: the gut (digestive tract), mouth, skin, nose and vagina.


Whilst most of the huge numbers of bacteria present in the human body at any one time are ‘commensal’ bacteria – that is, non-pathogenic – their role is nevertheless thought to be important for health, not least because they may be beneficial for normal processes such as digestion. Sequences from the human gut microbiome were described earlier this year (see previous news). Now a new paper in Science reports on 178 microbial genome sequences from a range of body sites, and analysis of their possible protein products and functions [The Human Microbiome Jumpstart Reference Strains Consortium. Science 2010 328(5981): 994-999]. This included construction of a ‘pan-genome’, being the ‘sum of the core genes shared among all sequenced members of the species and the dispensable genes, or those genes unique to one or more strains studied’ for a few bacterial species for which multiple sequences were available


The analysis identified nearly 31,000 unique peptides (short proteins) of which just under 30,000 were previously unknown. Comparative analysis of previously sequenced, publicly available microbial data allowed identification of fewer than half this number. The function of most of the novel bacterial genes and gene products has yet to be investigated, but the researchers reportedly found that some peptides produced by gut bacteria might be involved in the formation of gastric ulcers, whilst others could be linked to metabolic processing of food components (see press release).


Comment: Although the results presented in this paper do not reveal much about the role of the microbiome in health and disease, they represent important ground work (including the development of methods, standards and infrastructure) needed to allow the next stages of research, including into links between the presence or absence of specific microbial species in certain locations and particular states of health or disease. Samples will also be taken from additional locations within the body, the blood and male urethra. The growing collection of reference genomes from the human microbiome will allow researchers to compare microbial sequence data to identify genuinely novel microbial genes more easily than at present.


An even larger group, the International Human Microbiome Consortium (IHMC), which includes the US HMP centers as well as other efforts including the EU MetaHIT project, is collectively seeking to sequence a total of more than 1000 bacterial reference genomes from the human microbiome.

Research article   |   By Dr Sowmiya Moorthie   |   Published 21 May 2010

Synthetic biology refers to the artificial construction of novel biological systems or organisms building on genetic engineering techniques. Recently scientists at the J. Craig Venter Institute (JCVI) have demonstrated the possibility of creating a bacterial cell controlled by a synthetic genome (see BBC news). In a paper published in Science, the authors describe a proof of principle process for the synthesis, assembly, cloning and transplantation of a synthetic bacterial genome derived from the bacterium M.mycoides [Gibson et al. (2010) Science doi: 10.1126/science.1190719]. This builds on previous work in which they demonstrated the assembly of synthetic bacterial chromosomes in yeast and transplantation of a bacterial genome from one species to another (see previous news).

The initial step involved computer analysis of the genome of M. mycoides in order to design multiple segments of DNA that were then synthesised artificially and assembled to produce a synthetic chromosome. The synthetic M. mycoides genome was then transplanted into another bacterial species – M. capricolum, creating a hybrid cell. Cells that were controlled solely by the genome of M.mycoides were obtained following several rounds of bacterial replication during which the M. capricolum DNA was lost or destroyed. Analysis of these cells showed that they replicated normally and had similar properties to natural M.mycoides cells. The JCVI scientists envision that this technology will “lead to the development of many important applications and products including biofuels, vaccines, pharmaceuticals, clean water and food products” (see press release).

Synthetic biology is an area of simultaneous interest and concern for many countries; for example, a UK report examined the social and ethical challenges posed by such research (see previous news). Last year participants at an international symposium discussed opportunities and challenges posed by this field, with an aim to identify issues and areas for future study and help generate policy-level discussion. A report of the proceedings drafted by the OECD and the UK Royal Society has now been released. Participants recognised the need to invest in this emerging field as well developing policies for standardisation and international collaboration in regulation and governance. They also recognised the need for public engagement strategy and to discuss both the technical as well as ethical and social aspects of this technology.

Comment: Some applications of synthetic biology have obvious benefits, such as the production of drug-like molecules or biofuels, whilst others are highly contentious, for example the creation of new forms of life such as viruses (including as potential bioweapons). Media reports on the creation of a synthetic bacterial genome have raised many of these concerns, particularly in relation to the creation of new forms of life, although in fact the study by Gibson et al. did not actually create an entirely new synthetic life-form. In addition, many of the potential applications of synthetic biology that have provoked concern are already in use, albeit using alternative technologies. Genetic engineering techniques have been used in the production of modified organisms to derive genetically modified foods, inter-species embryos (see previous news) and more recently have led to a technique to combat mitochondrial diseases (see previous news). Hence, many issues are not unique to synthetic biology, having already been raised in the context of other scientific advances, and processes to ensure safe and appropriate development are already in use or development.

Research article   |   By Dr Susmita Chowdhury   |   Published 14 May 2010

One in three people in the UK die from Cardiovascular disease which is the leading cause of death in the UK, and about half of all these deaths are due to coronary heart disease or CHD (see Heartstats website). Established risk factors for coronary heart disease (CHD) include high levels of LDL (low-density lipoproteins) or cholesterol, or low levels of HDL (high-density lipoproteins) in the blood. There has been conflicting evidence about whether increased triglyceride concentration is also a risk factor for CHD; triglycerides are the most common type of fat in the blood plasma the key component of low-density lipoprotein (VLDL). In many epidemiological studies, an apparent association between triglycerides and CHD was lost after controlling for HDL and LDL levels. Moreover, previous genetic studies have shown that a polymorphism in the promoter region of the apolipoprotein A5 gene (APOA5) is associated with elevated triglyceride levels, but were not able to assess potential disease causality.

A new paper reports the use of a novel approach called Mendelian randomisation analysis (which uses genetic information to mimic aspects of a randomised drug trial - see previous news) on a large sample of 350000 people across 101 studies, which supports a causal association between high levels of triglyceride in the blood and CHD [Sarwar N et al. (2010) Lancet 375(9726):1634-9].

The investigators first measured the effect of a single–nucleotide polymorphism (SNP) in the APOA5 gene on triglyceride concentrations and other risk factors (levels of LDL, HDL, cholesterol etc.) using data from more than 73,000 individuals in 39 studies, and found it was strongly related to increased triglyceride concentration, but either moderately or unrelated to other risk factors. They then assessed the association of the same APOA5 SNP directly with the risk of CHD by meta-analysis of around 21,000 cases and 35,000 controls, and found there was an 18% increased risk of disease for each copy of the SNP present.

Finally, they estimated the risk of CHD conferred by an increase in triglyceride concentrations similar to that observed in the first analysis in over 300,000 individuals, among whom a total of nearly 13,000 CHD events occurred. The CHD risk was found to increase in line with rising levels of circulating blood triglycerides, and the APOA5 SNP linked to biological pathways through which triglyceride could affect CHD. The authors proposed that their findings were consistent with a causal relationship between increased levels circulating triglycerides and CHD.

Comment: Mendelian randomisation assumes a simple model of causality, which may not be borne out in reality, and other complicating factors may also have influenced the results. Another limitation of this study is that the data used was from mostly European subjects, and so the results may not be generalisable to other populations. Other concerns also exist; for example, the APOA5 polymorphism might have a direct effect on CHD risk and pathogenesis (besides the effect on triglyceride levels), which could have a confounding effect on the findings. Although further investigation of the ‘triglyceride risk’ is called for, with the authors recommending large randomised trials of triglyceride-lowering medications before a final conclusion on the potentially causal effect of triglyiceride levels on CHD, their report is nevertheless one of the largest and most comprehensive studies to date showing an association between triglycerides and CHD. 

Research article   |   By Dr Gurdeep Sagoo   |   Published 10 May 2010

Breast cancer is the most common cancer in women in the UK with around 45,700 women diagnosed in 2007 (according to the leading charity Cancer Research UK). A new study published online in the journal Nature Genetics has identified five novel breast cancer susceptibility loci taking the number of identified genetic variants associated with susceptibility up to 18 [Turnbull et al. (2010) Nature Genetics 9 May; doi:10.1038/ng.586].

Turnbull et al. conducted a genome-wide association study (GWAS) in which almost 600,000 SNPs were genotyped in more than 3,500 breast cancer cases with a positive family history and nearly 5,000 controls. In addition to finding associations with all 13 of the previously identified loci, a further 28 SNPs in 13 regions were also identified. Once linkage disequilibrium was accounted for, 15 SNPs were assessed in the replication sample of over 12,500 cases and over 12,000 controls. Five of these SNPs from five loci on chromosomes 9, 10, and 11 (three loci on chromosome 10) showed evidence of replication with statistically significant results (with P-values ranging from 4.6 x 10-7 to 3.2 x 10-15).

Four of the five SNPs showed stronger association for oestrogen receptor-positive breast cancer cases with little association with oestrogen receptor-negative cases, although this is a pattern observed with the majority of breast cancer loci identified thus far. The authors identified 13 plausible candidate genes across these loci with some genes also showing associations with other cancers (such as malignant melanoma or pancreatic cancer). These five loci when combined with the 13 other common disease susceptibility loci help explain approximately 8% of the familial risk of breast cancer (with a further 20% explained by the rarer mutations in BRCA1 and BRCA2).

Comment: This well conducted GWAS provides evidence for an additional five common breast cancer susceptibility loci in what is the largest breast cancer GWAS conducted to date. However, these novel loci are only estimated to account for an additional 1.2% of familial risk. When taken with the other known common and rare associated loci, around 30% of familial risk is explained with the authors emphasising that the remaining “familial risk is therefore likely to be due to a combination or a large number of common variants with smaller effects together with rarer variants not testable with current arrays” along with epigenetic and other shared environmental factors.

Although unlikely to improve the usefulness of predicting genetic risk at an individual level, the newly identified susceptibility variants could prove beneficial for stratifying the general female population for more effective targeting of screening programmes to those at greatest risk of breast cancer (see previous news). The PHG Foundation is a partner in a large European consortium, the Collaborative Oncological Gene-environment Study (COGS), a project that is developing the understanding of both genetic and environmental risk factors for breast, ovarian and prostate cancers, for use in individual risk prediction.

Research article   |   By Dr Sowmiya Moorthie   |   Published 5 May 2010

Paget’s disease of the bone (PDB) is a painful chronic disorder that typically results in enlarged and deformed bones. It is caused by the excessive breakdown and formation of bone tissue, which can also lead to weakened bones and arthritis. PDB is a late onset disease and is usually diagnosed in people over 40. Although the underlying cause is yet to be identified, it is thought to have a genetic component, as 15-20% of those affected have a first degree relative who is also affected.

Mutations in the SQSTM1 gene have been identified in some patients with PDB; however, linkage analysis has failed to identify other genes that may predispose to this condition. Identification of genes that predispose to PDB would be advantageous for early detection, allowing preventative treatment to be initiated before onset of bone damage. A recent study in Nature Genetics reports on identification of three new genes that may be associated with PDB and could offer hopes of a screening test (reported by BBC news).

In their study Albagha et al. identified three new genetic loci that may predispose to PDB through a genome-wide association study [Albagha et al (2010) Nat. Genet. Epub]. In order to identify genes other than SQSTM1 associated with disease, samples from 750 cases without mutations in the SQSTM1 gene and 1002 controls were genotyped. This led to the identification of three candidate loci strongly associated with disease,  findings that were replicated in an independent set of 500 cases and 535 controls.

The candidate loci associated with disease included the CSF1, OPTN and TNFRSF11A genes. The CSF1 and TNFRSF11A gene products are candidates for PDB susceptibility as they are both involved in bone tissue formation and survival. Studies in rodents have shown that mutations in these gene lead to osteopetrosis (thickening of the bones). The function of OPTN in bone metabolism is as yet unknown, and further studies will be needed to establish a possible role in PDB. The researchers are undertaking further studies to elucidate the mechanism by which these genes influence disease and identify other genes that contribute to disease risk.

Comment: This study has used a different approach to identify possible genes that could increase risk for PDB and added to our knowledge of this condition. However, hopes for a screening test remain somewhat premature, since development would require identification of specific causal variants that are associated with disease and their validation in the general population in order to demonstrate their ability to correctly identify those who may be at increased risk of developing PDB.

Research article   |   By Dr Susmita Chowdhury   |   Published 4 May 2010

Cancer is acknowledged to be a major public health problem for both industrialised and developing nations, with more than a quarter of deaths attributable to cancer in many countries. According to the World Health Organisation (WHO), cancer rates could increase to 12 million new cases by 2030.


The genomes of all cancer cells accumulate somatic mutations and epigenetic markers; each tumour has its own unique genetic make-up. In addition to studying genetic features that may be shared by classes and sub-classes of cancers, researchers are also investigating personalised approaches to care for individual patients. Now, cancer genome scientists from across the globe have launched a collaboration to decode the genomes from 25,000 different cancer cell samples, the results to be made freely available to researchers.


The recent publication in Nature [Nature 464, 993-998 (15 April 2010) | doi:10.1038/nature08987] by the International Cancer Genome Consortium (ICGC) outlines a set of strategies and policies needed to implement the goals of the ICGC (see previous news).The main goal is to generate comprehensive catalogues of genomic abnormalities in 50 different clinically and socially important cancer types or subtypes. Project aims include ensuring high quality, standardised data collection and accelerating dissemination of datasets and analytical methods. It is expected that the ICGC catalogues will grow exponentially and will have immediate relevance in the cancer research community.


The ICGC has taken care to address bioethical issues involved in the use of genomic data, recognising the delicate balance between protecting the interests and rights of the sample donors and their relatives, and sharing the data to accelerate cancer research and maximise public benefit. Data access policies and ethics have been outlined in detail and two levels of access: ‘open access’ and ‘controlled access’ data sets will be available (by mid-2010). Though the ICGC encourage the scientific community to use any data without any restriction, ICGC members will be allowed the opportunity to be the first to publish global analyses from the datasets they generate.


At present, two European consortia and 10 other countries including Australia, Canada, China, India, Japan, UK and USA have initiated cancer genome projects under the umbrella of the ICGC.  

Research article   |   By Dr Caroline Wright and Dr Gurdeep Sagoo   |   Published 2 May 2010

Twin studies have historically been used in order to help disentangle the role of genetic and environmental factors on disease, and discordant twins (where one twin has a particular disease but the other doesn’t, or develops it at a much later age) are particularly useful for this purpose. Monozygotic (identical) twins essentially share their entire genetic makeup, while dizygotic (non-identical) twins share approximately half their genetic makeup, with the assumption that both types of twin essentially share their in utero and environmental exposures.


A new study published in Nature, compared the genomes, epigenomes, and transcriptomes of three pairs of identical twins discordant for multiple sclerosis (MS) including the full sequencing of a one (female) pair [Baranzini et al. (2010) Nature 464:1351-6]. Multiple sclerosis (MS) is an autoimmune disease leading to disability and neurodegeneration in young adults, in which both environment factors (such as viral infection) and genetic susceptibility are known to play a key role, with both human leukocyte antigen system (HLA) and non-HLA loci showing previous associations. By analysing and comparing the twin’s HLA regions, genome-wide single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), white blood cell DNA methylation and gene expression profiles, and even whole genomes in one pair, the authors hoped to uncover important clues about the underlying aetiology of MS. Surprisingly, however, they were unable to find any variation in genomic or epigenomic factors, or even differences in gene expression, within each twin pair that could be used to explain their disease discordance.


Comment: This is the first in-depth comparison between the genomes of two identical twins. Somewhat disappointingly, the research essentially showed that the discordance in disease seemed to have no detectable causal genetic or epigenetic basis. This essentially negative result is nonetheless extremely important, and highlights the fact that comprehensive genetic analysis will not provide the panacea that many seem to believe, and won’t always yield clear answers about the underlying basis of complex conditions. While it may be relatively unsurprising that identical twin pairs do not have major genetic differences, despite recent research indicating differing CNV profiles [Bruder CE, et al. (2008) Am J Hum Genet 82:763-71], the lack of substantial epigenetic differences or varying levels of gene expression in the white blood cells tested is rather unexpected.


Nonetheless, “there has to be some trigger that catalysed one to develop [the disease] and the other not” said first author Sergio Barazani in an accompanying news article in Nature, adding that a possible explanation is that “one [twin] was exposed to the perfect combination of environment triggers”. Given the relatively late age of onset of the disease, there may actually have been quite large differences in environmental exposures between the twins. Like many diseases, a complex web of genetic and environmental factors and their interactions may be critical to the underlying cause of MS.

New reviews and commentaries

Selected new reviews and commentaries, 4 May 2010

Reviews & commentaries : by Dr Philippa Brice
Nature special edition: The Human Genome at Ten


Big Science: The cancer genome challenge

Ledford H. Nature. 2010 Apr 15;464(7291):972-4.


Confidentiality and sharing genetic information with relatives.

Lucassen A, Parker M. Lancet. 2010 May 1;375(9725):1507-9. 


The personal genome - the future of personalised medicine?

Samani NJ, Tomaszewski M, Schunkert H. Lancet. 2010 May 1;375(9725):1497-8.


Ethics. DNA returned to tribe, raising questions about consent.

Couzin-Frankel J. Science. 2010 Apr 30;328(5978):558


Screening disease away.

Couzin-Frankel J. Science. 2010 Apr 16;328(5976):300.


Chasing a disease to the vanishing point.

Couzin-Frankel J. Science. 2010 Apr 16;328(5976):298-300.


Putting patients before patents.

Evans JP. Genet Med. 2010 Apr;12(4 Suppl):S3-4.


Myriad Genetics: In the eye of the policy storm.

Gold ER, Carbone J. Genet Med. 2010 Apr;12(4 Suppl):S39-70.


Copy number variation and human genome maps.

McCarroll SA. Nat Genet. 2010 May;42(5):365-6.


Chipping away at the genetics of smoking behavior.

Amos CI, Spitz MR, Cinciripini P. Nat Genet. 2010 May;42(5):366-8


Let parents decide.

Handyside A. Nature. 2010 Apr 15;464(7291):978-9.


Synthetic biology: applications come of age.

Khalil AS, Collins JJ. Nat Rev Genet. 2010 May;11(5):367-79.


Genome-wide association studies in diverse populations.

Rosenberg NA et al. Nat Rev Genet. 2010 May;11(5):356-66.


Genetic kidney diseases.

Hildebrandt F. Lancet. 2010 Apr 10;375(9722):1287-95.


Genetic susceptibility to hepatic steatosis.

Diehl AM. N Engl J Med. 2010 Mar 25;362(12):1142-3

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