Researchers at King’s College London have for the first time identified a gene linked to age-related degeneration of the intervertebral discs in the spine, a common cause of lower back pain.

Costing the UK an estimated £7billion a year due to sickness leave and treatment costs, the causes of back pain are not yet fully understood. Until now, the genetic cause of lower back pain associated with lumbar disc degeneration (LDD) was unknown, but the largest study to date, published this week in the journal Annals of Rheumatic Diseases, has revealed an association with the PARK2 gene.

The researchers, funded by the Wellcome Trust and Arthritis Research UK, say more research into this surprising association needs to be carried out in order to fully understand how it is triggered, but this new finding could ultimately pave the way towards developing new treatments in the future.

LDD is a common age-related trait, with over a third of middle-aged women having at least one degenerate disc in the spine. Discs become dehydrated, lose height and the vertebrae next to the discs develop bony growths called osteophytes. These changes can cause or contribute to lower back pain. LDD is inherited in between 65 – 80 per cent of people with the condition, suggesting that genes play a key role.

Scientists compared MRI images of the spine in 4,600 individuals with genome-wide association data, which mapped the genes of all the volunteers. They identified that the gene PARK2 was implicated in people with degenerate discs and could affect the speed at which they deteriorate.

The researchers say the results show that the gene may be switched off in people with LDD. Although it is still unclear how this might happen, it is thought that environmental factors, such as lifestyle and diet, could trigger this switch by making changes known as epigenetic modifications to the gene.

Dr Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s College London, said: ‘Back pain can have a serious impact on people’s lives and is one of the most common causes of sickness leave, costing both the NHS and UK economy billions each year.

‘We have performed, using data collected from around the world, the biggest genome-wide association analysis of lumbar disc degeneration (LDD). We know that people whose discs wear out are at increased risk of episodes of lower back pain, but normal human discs are hard to get hold of to study so until now our knowledge of normal human biology was incomplete.

‘We have identified a gene called PARK2 as associated with LDD. We have shown that the gene may be switched off in people with the condition.

‘Further work by disc researchers to define the role of this gene will, we hope, shed light on one of most important causes of lower back pain. It is feasible that if we can build on this finding and improve our knowledge of the condition, we may one day be able to develop new, more effective treatments for back pain caused by this common condition.’

Notes to editors

View the paper, ‘Novel genetic variants associated with lumbar disc degeneration in northern Europeans’.

For further information or to interview Dr Frances Williams, please contact Emma Reynolds, PR Manager (Health) at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk.

For further information about King’s visit our ‘King’s in Brief’ page.

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

Arthritis Research UK is the leading authority on arthritis in the UK, conducting scientific and medical research into all types of arthritis and musculoskeletal conditions. It is the UK’s fourth largest medical research charity and the only charity solely committed to funding high quality research into the cause, treatment and cure of arthritis.

Researchers identify key genes that switch off with ageing, highlighting them as potential targets for anti-ageing therapies.

Researchers at King’s College London, in collaboration with the Wellcome Trust Sanger Institute, have identified a group of ‘ageing’ genes that are switched on and off by natural mechanisms called epigenetic factors, influencing the rate of healthy ageing and potential longevity.

The study also suggests these epigenetic processes – that can be caused by external factors such as diet, lifestyle and environment – are likely to be initiated from an early age and continue through a person’s life. The researchers say that the epigenetic changes they have identified could be used as potential ‘markers’ of biological ageing and in the future could be possible targets for anti-ageing therapies.

Published today in PLoS Genetics, the study looked at 172 twins aged 32 to 80 from the TwinsUK cohort based at King’s College London and St Thomas’ Hospital, as part of King’s Health Partners Academic Health Sciences Centre.

The researchers looked for epigenetic changes in the twins’ DNA, and performed epigenome-wide association scans to analyse these changes in relation to chronological age. They identified 490 age related epigenetic changes. They also analysed DNA modifications in age related traits and found that epigenetic changes in four genes relate to cholesterol, lung function and maternal longevity.

To try to identify when these epigenetic changes may be triggered, the researchers replicated the study in 44 younger twins, aged 22 to 61, and found that many of the 490 age related epigenetic changes were also present in this younger group. The researchers say these results suggest that while many age related epigenetic changes happen naturally with age throughout a person’s life, a proportion of these changes may be initiated early in life.

Dr Jordana Bell from King’s College London, who co-led the study said: ‘We found that epigenetic changes associate with age related traits that have previously been used to define biological age. ‘We identified many age-related epigenetic changes, but four seemed to impact the rate of healthy ageing and potential longevity and we can use these findings as potential markers of ageing. These results can help understand the biological mechanisms underlying healthy ageing and age-related disease, and future work will explore how environmental effects can affect these epigenetic changes.’

Dr Panos Deloukas, co-leader of the study from the Wellcome Trust Sanger Institute, said: ‘Our study interrogated only a fraction of sites in the genome that carry such epigenetic changes; these initial findings support the need for a more comprehensive scan of epigenetic variation.’

Professor Tim Spector, senior author from King’s College London, said: ‘This study is the first glimpse of the potential that large twin studies have to find the key genes involved in ageing, how they can be modified by lifestyle and start to develop anti-ageing therapies. The future will be very exciting for age research.’

Further information Emma Reynolds, Press Officer King’s College London Email: emma.reynolds@kcl.ac.ukTel: 0207 848 4334

A copy of the PLoS Genetics paper can be accessed here.

For more information about King’s please click here.

A report by Professor Barbara Prainsack and Dr Alena Buyx reflects on how solidarity plays a role in our society and can facilitate policy making in areas affecting biobanks, pandemics and lifestyle diseases.

A team of researchers, led by King’s College London and the University of Oxford, have found that a gene linked to type 2 diabetes and cholesterol levels is in fact a ‘master regulator’ gene, which controls the behaviour of other genes found within fat in the body.

As fat plays a key role in susceptibility to metabolic diseases such as obesity, heart disease and diabetes, this study highlights the regulatory gene as a possible target for future treatments to fight these diseases.

Published today in Nature Genetics, the study was one part of a large multi-national collaboration funded by the Wellcome Trust, known as the MuTHER study. It involves researchers from King’s College London, University of Oxford, The Wellcome Trust Sanger Institute, and the University of Geneva. DeCODE Genetics also contributed to the results reported in this paper.

It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located further away on the genome was unknown.

The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects.

These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), cholesterol, insulin and glucose levels, highlighting the interconnectedness of metabolic traits.

The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents. But in this case, the copy of KLF14 from the father is switched off, meaning that the copy from the mother is the active gene – a process called imprinting. Moreover, the ability of KLF14 to control other genes was entirely dependent on the copy of KLF14 inherited from the mother – the copy inherited from the father had no effect.

Professor Tim Spector from the Department of Twin Research at King’s, who led the MuTHER project, said: ‘This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes. This has great therapeutic potential particularly as by studying large detailed populations such as the twins we hope to find more of these regulators.’

Professor Mark McCarthy from the University of Oxford, who co-led the study, said: ‘KLF14 seems to act as a master switch controlling processes that connect changes in the behaviour of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions. We are working hard right now to understand these processes and how we can use this information to improve treatment of these conditions.’

For further information please contact Emma Reynolds, Press Officer at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

A copy of the Nature Genetics paper is available on request.

Notes to editors

The MuTHER study stands for the Multiple Tissue Human Expression Resource study and is a five year program grant funded by the Wellcome Trust. The consortium involves over 30 scientists from the UK and Switzerland. The coordinator is Professor Spector at King’s and the other lead PIs are Professor McCarthy at Oxford, Dr Deloukas at the Wellcome Trust Sanger Institute in Hinxton and Professor Demitzakis at University of Geneva. 850 female twins have had skin, fat and blood cells collected as well as hundreds of clinical traits assessed. The overall aim of the study is to use the unique detailed genetic, genomic and phenotypic data generated from the TwinsUK study to understand the mechanisms of how genes influence common age-related and metabolic diseases. (http://www.muther.ac.uk/)

King’s College London

King’s College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times ‘University of the Year 2010/11′ and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org/.

Oxford University’s Medical Sciences Division

Oxford University’s Medical Sciences Division is recognised internationally for its outstanding research and teaching, attracting the brightest minds from all over the world.

It is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students, and brings in around two-thirds of Oxford University’s external research income. Listed by itself, that would make it the fifth largest university in the UK in terms of research grants and contracts.

Oxford is home to the UK’s top-ranked medical school, and partnerships with the local NHS Trusts enable patients to benefit from the close links between medical research and healthcare delivery.

14 winners of the Nobel Prize for Physiology or Medicine worked or were educated at Oxford, and the division is home to 29 Fellows of the Royal Society and 68 Fellows of the Academy of Medical Sciences.

Past successes include the development of penicillin, which ushered in the modern age of antibiotics, and the confirmation of the link between smoking and cancer, which has prevented many millions of deaths. Oxford continues to be at the forefront of medical research, whether it’s the genetic and molecular basis of disease, the latest advances in neuroscience, or clinical studies in cancer, diabetes, heart disease and stroke. Oxford has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic.

A major strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies into the causes and treatment of cancer, heart disease, diabetes and other common conditions.

The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. For more information, visit: http://www.wellcome.ac.uk/

Eight genes which control levels of the main steroid produced by the adrenal gland, believed to play a role in ageing and longevity, have been uncovered by an international consortium of scientists, co-led by King’s College London.

Crucially, some of these eight genetic regions are also associated with other important diseases of ageing, including type 2 diabetes and lymphoma. Researchers say that these findings, published in the journal PLoS Genetics today, provide the first genetic evidence for the ageing role of the steroid, and therefore highlights it as a marker of biological ageing.

It was already known that the concentration of the steroid dehydroepiandrosterone sulphate (DHEAS), declines rapidly with age – it diminishes by 95 per cent by the age of 85. This has led to speculation that a relative DHEAS deficiency may contribute to common age-related diseases or diminished longevity.

To explore the mechanisms behind declining levels of the steroid, the researchers carried out an analysis of DHEAS levels and 2.5 million genetic variants in 14,846 people from Europe and USA. They found eight common genes that control the blood concentration of DHEAS, and importantly some of these genes are associated with ageing and common age-related diseases such as type 2 diabetes and lymphoma.

Lead author, Dr Guangju Zhai from King’s College London, said: ‘This is the first large-scale study to unlock the mystery that has always surrounded DHEAS. We have identified specific genes that control its concentration levels, and shown that some of these are also involved in the ageing process and age-related diseases.

‘The findings provide us with the basis for future studies to look into potential mechanisms of exactly how the DHEAS is involved in ageing. The next important question to try and answer is whether sustained high levels of DHEAS can in fact delay the ageing process and prevent age-related diseases.’

‘Professor Tim Spector, senior co-author from King’s, said: ‘This study shows the power of collaborative genetic studies to uncover mechanisms of how the body works. For 50 years we have observed the most abundant circulating steroid in the body, DHEAS, with no clue as to its role. Now its genes have shown us its importance in many parts of the ageing process.’

Notes to editors

King’s College London

King’s College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times ‘University of the Year 2010/11′ and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:www.kingshealthpartners.org.

Further information
Emma Reynolds
Press Officer at King’s College London
Email: emma.reynolds@kcl.ac.uk
Tel: 0207 848 4334

Scientists have identified a gene that appears to play a role in regulating how much alcohol people drink, in a study of over 47,000 people published today in Proceedings of the National Academy of Sciences.

The researchers say that finding a common genetic variation influencing levels of alcohol consumption may lead to a better understanding of mechanisms underlying alcohol drinking behaviour in the general population.

The gene, called autism susceptibility candidate 2, or AUTS2, has previously been linked to autism and attention deficit hyperactivity disorder, but its function is not known.

Today’s study, by an international consortium led by scientists at King’s College London and Imperial College London, found that there are two versions of the AUTS2 gene, one three times more common than the other. People with the less common version drink on average five per cent less alcohol than people with the more common version.

The gene is most active in parts of the brain associated with neuropsychological reward mechanisms, suggesting that it might play a part in regulating the positive reinforcement that people feel when they drink alcohol.

Alcohol consumption is known to be partly determined by genes but until now the only gene known to make a notable contribution was the gene encoding alcohol dehydrogenase, an enzyme that breaks down alcohol in the liver.

Professor Günter Schumann, from the Institute of Psychiatry at King’s College London, said: ‘In this study we combine genetic studies with investigations of animal behaviour. Since people drink alcohol for very different reasons, understanding the particular behaviour influenced by the gene identified helps us better understand the biological basis of these reasons. This is an important first step towards the development of individually targeted prevention and treatments for alcohol abuse and addiction.’

The researchers analysed DNA samples from over 26,000 volunteers to search for genes that appeared to affect alcohol consumption, and then checked their findings in another 21,000 people. The volunteers reported how much alcohol they drank in questionnaires.

Once the researchers had identified AUTS2, they examined how much messenger RNA –a copy of the gene’s code that is used to make a protein – was present in samples of donated human brain tissue. They found that the people with the version of the gene associated with lower alcohol consumption produced more of the messenger RNA, meaning that the gene was more active.

The researchers also investigated strains of mice that had been selectively bred according to how much alcohol they drink voluntarily. They found that there were differences in the AUTS2 gene activity levels among different breeds of mice that drink more or less alcohol. In addition, the researchers found that blocking the effect of a related gene in fruit flies made the flies less sensitive to alcohol. These results indicate that AUTS2 seems to be involved in regulation of alcohol intake in a number of different species.

Professor Paul Elliott, from the School of Public Health at Imperial College London, said: ‘Of course there are a lot of factors that affect how much alcohol a person drinks, but we know from twin studies that genes play an important role. The difference that this particular gene makes is only small, but by finding it we’ve opened up a new area of research into the biological mechanisms that control drinking.’

The research was principally funded by the National Institute for Health Research Biomedical Research Centres at Imperial and the South London and Maudsley NHS Foundation Trust/King’s College London, as well as the European Commission and the Medical Research Council.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption by G. Schumann et al. is published in Proceedings of the National Academy of Sciences.

Notes to editors

King’s College London

King’s College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times ‘University of the Year 2010/11’ and the fourth oldest in England. A research-led university based in the heart of London, it has nearly 23,500 students (of whom nearly 9,000 are graduate students) from 140 countries and approximately 6,000 employees.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

Further information
Louise Pratt
King’s College London
Email: louise.a.pratt@kcl.ac.uk
Tel: 0207 848 5378

Researchers at King’s College London and the University of East Anglia have discovered that women who consume a diet high in allium vegetables, such as garlic, onions and leeks, have lower levels of hip osteoarthritis.

The findings, published in the BMC Musculoskeletal Disorders journal, not only highlight the possible effects of diet in protecting against osteoarthritis, but also show the potential for using compounds found in garlic to develop treatments for the condition.

A relationship between body weight and osteoarthritis was previously recognised, although it is not yet completely understood. This study is the first of its kind to delve deeper into the dietary patterns and influences that could impact on development and prevention of the condition.

Osteoarthritis is the most common form of arthritis in adults, affecting around 8 million people in the UK, and women are more likely to develop it than men. It causes pain and disability by affecting the hip, knees and spine in the middle-aged and elderly population. Currently there is no effective treatment other than pain relief and, ultimately, joint replacement.

The study, funded by Arthritis Research UK, the Wellcome Trust and Dunhill Medical Trust, looked at over 1,000 healthy female twins, many of whom had no symptoms of arthritis.

The team carried out a detailed assessment of the diet patterns of the twins and analysed these alongside x-ray images, which captured the extent of early osteoarthritis in the participants’ hips, knees and spine.

Healthy diet

They found that in those who consumed a healthy diet with a high intake of fruit and vegetables, particularly alliums such as garlic, there was less evidence of early osteoarthritis in the hip joint.

To investigate the potential protective effect of alliums further, researchers studied the compounds found in garlic. They found that that a compound called diallyl disulphide limits the amount of cartilage-damaging enzymes when introduced to a human cartilage cell-line in the laboratory.

Dr Frances Williams, lead author from the Department of Twin Research at King’s College London, says: ‘While we don’t yet know if eating garlic will lead to high levels of this component in the joint, these findings may point the way towards future treatments and prevention of hip osteoarthritis.

‘It has been known for a long time that there is a link between body weight and osteoarthritis. Many researchers have tried to find dietary components influencing the condition, but this is the first large scale study of diet in twins. If our results are confirmed by follow-up studies, this will point the way towards dietary intervention or targeted drug therapy for people with osteoarthritis.’

Professor Ian Clark of the University of East Anglia said: ‘Osteoarthritis is a major health issue and this exciting study shows the potential for diet to influence the course of the disease. With further work to confirm and extend these early findings, this may open up the possibility of using diet or dietary supplements in the future treatment osteoarthritis.’

Notes to editors

The paper, ‘Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action’ published in BMC Musculoskeletal Disorders can be found here: http://www.biomedcentral.com/1471-2474/11/280/abstract

King’s College London

King’s College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times ‘University of the Year 2010/11′ and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:www.kingshealthpartners.org.

The Dunhill Medical Trust

The Dunhill Medical Trust is a grant-making charitable trust established in 1986. The Trust originated from the Will Trust of Herbert Edward Dunhill who died in November 1950, leaving funds for the furtherance of medical knowledge and research. DMT welcomes high quality grant applications which fall within its charitable objects, particularly those within the following areas: care of older people, including rehabilitation and palliative care; and research into the causes and treatments of disease, disability and frailty related to ageing. For further information:www.dunhillmedical.org.uk. E-mail: admin@dunhillmedical.org.uk

Further information
Emma Reynolds
Press Officer at King’s College London
Email emma.reynolds@kcl.ac.uk
Tel: 0207 848 4334

Or

Simon Dunford
University of East Anglia
Email S.Dunford@uea.ac.uk
Tel: 01603 592203

One of the most ambitious large-scale projects in Human Genetics has been launched today: Epitwin will capture the subtle epigenetic signatures that mark the differences between 5,000 twins on a scale and depth never before attempted, providing key therapeutic targets for the development of drug treatments.

The project is a collaboration between TwinsUK, a leading twin research group based at King’s College London, and BGI, one of the world’s largest genomic organisations headquartered in Shenzhen, China. Epigenetics is the most cutting edge emerging field in Genetics, which explores how the actions of genes can be temporarily modified by chemical reactions that may occur either at random or by lifestyle or diet. This effect may last several generations.

The plan is to look at the methylation patterns of 20 million sites (called CpG islands) in the DNA of each twin and compare them with the patterns in the co-twin. Rather than looking at similarities as in previous studies, the team will be looking for differences that explain why many identical twins don’t develop the same diseases. Initially the team will focus on obesity, diabetes, allergies, heart disease, osteoporosis and longevity, but the method can be applied to every common trait or disease.

Finding key genetic ‘switches’

‘Finding the crucial differences between twins will lead us to the key genes that are being turned on and off, and so to the cause of disease, with great potential to find key targets for drug treatments,’ says Tim Spector, Director of TwinsUK and Professor of Genetic Epidemiology at King’s College London, who is the co-leader of the project.

‘The fact that twins are such a marvellous natural experiment, combined with the hundreds of disease details and traits on the twins that we have collected over 17 years, offer a unique study opportunity. So far this type of study has only been attempted on a handful of twins, so we want to scale it up – one thousand fold.’

The Executive Director of BGI and co-leader of the project is Professor Jun Wang, whose team completed the sequencing of many diverse species, including an Asian individual, the Giant Panda, the rice genome, the silkworm genome, and the genomes of the cucumber and ant. He is excited about the study: ‘Epigenetics is one of our major targets for the next five years – and this combination of our technology and resources with the unique twin resource will provide the world with an unprecedented dataset. We hope to unlock many secrets about human genetics that we don’t currently understand, and to accelerate research and applications in human healthcare.’

The project is expected to cost around £20 million ($30 million). These costs are being shared by the groups, and supported by a Senior Investigator award to Professor Spector for the Epitwin project by the European Research Council.

Notes to editors

The Department of Twin Research and Genetic Epidemiology

King’s College London’s Department of Twin Research and Genetic Epidemiology (DTR) encompasses the biggest UK adult twin registry of 11,000 twins used to study the genetic and environmental aetiology of age related complex traits and diseases. The DTR has been one of the major departments of King’s Division of Genetics and Molecular Medicine since 2006 with a team of over 40 staff.

The Department has a voluntary database of 10,000 identical and non-identical, mostly female, twins from across the UK between the ages of 16 and 85 years – with a mean age of 48. It is now the UK’s only adult twin registry and is the most detailed clinical adult register in the world.

DTR has an international track record of research into the genetics of complex diseases with a particular focus on age-related diseases. Its current main focus is the genetics of metabolic syndrome and cardiovascular disease, the musculoskeletal system and ageing as well as research into sight and miscellaneous areas such as skin disease, immunology, gastroenterology and behaviour.

For more information visit www.twinsUK.ac.uk.

BGI

BGI (formerly known as Beijing Genomics Institute) was founded in Beijing in 1999 with the mission of supporting the development of science and technology, building strong research teams, and promoting the development of scientific partnership in genomics field.

With a goal toward excellence, high efficiency, and accuracy, BGI has successfully completed a large number of projects. These include sequencing one per cent of the human genome for the International Human Genome Project, contributing 10 per cent to the International Human HapMap Project, carrying out research to combat SARS, being a key player in the Sino-British Chicken Genome Project, and completely sequencing the rice genome, the silkworm genome, and, most recently, the first Asian diploid genome.

In 2007, in accordance with BGI’s goal for developing projects and platforms that are on the cutting edge of research and technologies, the organization’s headquarters was relocated to Shenzhen as the first citizen-managed, non-profit research institution in China.

For more information visit www.genomics.cn.

King’s College London

King’s College London is one of the top 25 universities in the world (Times Higher Education 2009) and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:www.kingshealthpartners.org.

Further information
Melanie Haberstroh
International Public Relations Officer
Email: melanie.haberstroh@kcl.ac.uk
Tel: 020 7848 3076

A world-wide consortium of researchers, including scientists from the Twin Research Unit at King’s College London, has identified 59 novel regions of the human genome that are involved in lipid metabolism. The concentrations of lipids, such as cholesterols, in the blood are the most important risk factors for Coronary Artery Disease (CAD).

This study represents the most comprehensive analysis to identify the biological underpinnings of lipoprotein metabolism. It aimed to find new biomarkers for lipid concentrations in the blood that can serve as indicators for an increased risk of developing CAD. These findings could provide the foundations for developing targeted drugs that suppress these key genes involved in metabolising the lipids, thereby preventing heart disease.

Men and women after menopause are at equal risk for developing CAD, which is currently the leading cause of death in the world, significantly impacting health, quality of life, and longevity. CAD develops when the arteries that supply blood to the heart muscle narrow through a build-up of lipids such as cholesterol, allowing less blood to flow through the arteries. As a result, the heart muscle lacks the blood and oxygen it needs, which can lead to chest pain or a heart attack. An estimated 1.5 million men and 1.2 million women in the UK live with the disease.

The researchers analysed the genome-wide association results for serum lipids in more than 100,000 individuals of European ancestry. In total, they identified 95 regions of the human genome, which include regions previously identified in other studies and 59 novel regions, that play a role in lipid metabolism. The study also demonstrated that some of these genetic locations were shared by European and non-European populations, thereby making the findings relevant on a global scale.

Dr Massimo Mangino of the Department of Twin Research & Genetic Epidemiology says: ‘This study represents a significant piece in the complex genetic jigsaw to understand the risks of developing Coronary Artery Disease. As this is the largest such study ever undertaken, with a sample that ensured international significance of the results, we are hopeful that it will provide a basis for further research into CAD biomarkers, and to enable new drugs to fight this dangerous condition.’

Notes to editors

Tanya M. Teslovich et al.: ‘Biological, clinical and population relevance of 95 loci for blood lipids’, Nature Volume 466 Number 7307. A copy of the paper is available on:http://www.nature.com/nature/journal/v466/n7307/full/nature09270.html

Petersen S., Peto V. and Rayner M. Coronary heart disease statistics. British Heart Foundation: London; 2004; quoted from http://www.coronaryarterydisease.co.uk

King’s College London

King’s College London is one of the top 25 universities in the world (Times Higher Education 2009) and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:www.kingshealthpartners.org.

Further information
Public Relations Department
Email: pr@kcl.ac.uk
Tel: 020 7848 3202

New research shows that genetic factors affect the risk of a person having vitamin D insufficiency. The research, which was jointly led by the Twin Research Unit at King’s College London and Harvard University, has been published online today and will also appear in an upcoming edition of The Lancet.

Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating vitamin D concentrations include sun exposure and diet, but previous work showing clustering of low vitamin D concentrations within families and twins suggests that genetic factors also play a part. In this study, the authors aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.

The authors did a genome-wide association study of almost 34,000 white people of European descent from 15 studies. A range of conventional techniques, including radioimmunoassay and mass spectrometry, were used to determine serum vitamin D concentrations. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L.

Variants at three genetic sites or ‘loci’ were significantly associated with vitamin D concentrations. These loci were near genes involved in cholesterol synthesis, vitamin D metabolism, and vitamin D transport. Participants with a genotype score (combining the three confirmed variants) in the highest quartile (the 25 per cent at greatest risk) were at two-and-a-half times increased risk of having vitamin D concentrations lower than 75 nmol compared with those in the lowest quartile (the 25 per cent at lowest risk).

Preventing health risks

Professor Tim Spector, Director of the Twin Research Unit at King’s College London comments: ‘Previous research had suggested that genetic factors could play a part in vitamin D insufficiency, as vitamin D insufficiency showed a high heritability. Our study confirms this based on the finding of a genetic link to low vitamin D levels. The improved understanding of vitamin D regulation from our study could help to identify those within the white population who are most at risk of vitamin D insufficiency. Vitamin D plays an important role for our health, so knowing who is most at risk may help to prevent certain health risks through extra supplementation.’

In their article the authors point out that the study included only white individuals of European descent. Whether the genetic variants identified also affect vitamin D status in other racial or ethnic groups is unknown and requires further study.

Notes to editors

The article ‘Common genetic determinants of vitamin D insufficiency: a genome-wide association study’ by Professor Tim Spector, King’s College London; Dr Elina Hyppönen, UCL Institute of Child Health; and Dr Thomas J Wang, Massachusetts General Hospital can be found on The Lancet website (www.thelancet.com). The research was undertaken in collaboration with international colleagues from the SUNLIGHT (Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits) consortium. SUNLIGHT is the biggest genetic epidemiology consortium for vitamin D worldwide.

King’s College London

King’s College London is one of the top 25 universities in the world (Times Higher Education 2009) and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:www.kingshealthpartners.org.

Further information
Public Relations Department
Email: pr@kcl.ac.uk
Tel: 020 7848 3202