The National Human Genome Research Institute catalog can now be accessed through your deCODEme account

Through your deCODEme account (or the demo account if you are not yet a deCODEme customer) you can access a catalog of published Genome-Wide Association Studies (GWAS) that has been compiled by the National Human Genome Research Institute (NHGRI).

This feature allows you to gain a quick overview of where research on common traits has been showing associations with single nucleotide genetic variations (SNPs).  Users can easily select a disease or trait from a list and a feature track with the corresponding SNPs from the catalog will show up in our Genome Browser.

Many of the associations in the GWAS catalog compiled in August 2009 are included in our Health Watch feature. There are also numerous other associations that our scientists have not included, as they do not fulfill the criteria we set for inclusion in our Health Watch.

The GWAS catalog is presented (see here) simply as it appears on the NHGRI web site and has not been reviewed by deCODE’s scientists. The catalog is provided primarily for educational purposes – for the curious George who wants to look at genome-wide association study results in the context of other information that we provide in our Genome Browser.

deCODEme Prostate Cancer

Last night we announced our discovery of four more SNPs linked to increased risk of prostate cancer. At the same time, academic collagues in the US and UK have also found more SNPs. (See article in TIMES ONLINE) All of the well-validated new risk variants will be incorporated into your deCODEme profile in the days ahead.

In the same study we published yesterday, we also conducted an analysis of all well-validated genetic risk factors discovered to date to establish what percentage of men would be at a significantly higher risk than average using these markers. Based upon our ability to swiftly conduct a population-based analysis in Iceland, this analysis demonstrates that about 4% of men are at more than double average risk based upon these risk factors, while just over 1% are at more than 2.5-times average risk.
Average lifetime risk of prostate cancer in Iceland is very similar to that of other populations of European descent, at about 12%. In light of the above calculations, that means that about 4% of men are at more that 20% lifetime risk based upon currently known risk SNPs, while slightly more than 1% of men are at more than 30% lifetime risk. Other standard measures of risk, such as age, family history, and PSA score, are all independent of the risk measured by common genetic risk factors, and so complement this risk calculation.

All of this is important to bear in mind as you check your own risk profile and consider what this information might mean to your health. Those of us who are deCODEme subscribers may well have wondered what it means when new risk factors are found, incorporated into our risk calculations, and your risk score changes. The answer is that for the vast majority of us, our increased risk of these common diseases is either slightly above or slightly below average. The numbers may change slightly, but this may not have any immediate bearing on how you should try to protect your health. At the same time, because these diseases are common, average risk is rarely insignificant, so we are none of us off the hook.

Yet it is for those in the highest risk categories that your profile may provide information that you can take to your doctor, and with him or her consider other risk factors you may have and evaluate how best to lower that risk or undergo appropriate screening.

As ever, we are eager to hear how you use your profile and how it may be helping you to take more control over your health. For our part, we will continue to integrate the best in genetics into your profile.

With best regards,
Edward Farmer
The deCODEme Team

deCODE-led Megastudy Finds New Genetic Clues to Causes of Schizophrenia. Findings expand knowledge of the biology of the disease and provide potential new drug targets.

The largest study of the genetics of schizophrenia ever undertaken has revealed several new common single-letter variants in the sequence of the human genome (SNPs) linked to risk of the disease. The study, by a multinational consortium of scientists led by a team from deCODE genetics, analyzed the genomes of more than 50,000 patients and control participants from fourteen countries. It is published today in the online edition of Nature.

One of the SNPs is located near the neurogranin gene (NRGN) on chromosome 11. NRGN may be a candidate drug target, as it appears to play an important role in regulating both memory and cognition, processes that are often perturbed in schizophrenics. Another SNP is in the transcription factor 4 (TCF4) gene on chromosome 18, which is involved in brain development. Five of the SNPs are located very closely together in the Major Histocompatibility Complex, a region on chromosome 6 densely packed with genes regulating immune response. This lends support to previous research suggesting a possible environmental link between schizophrenia immune response. It has long been known, for example, that a disproportionately large number of schizophrenics are born in the winter and spring, when influenza rates are usually highest. All of the variants found in this study are very common and each is associated with a modest increase in risk.

“Genetics offers a unique window for better understanding diseases like schizophrenia because the brain and cognition are so little understood and so difficult to study. Discoveries such as these are crucial for teasing out the biology of the disease and making it possible for us to begin to develop drugs targeting the underlying causes and not just the symptoms of the disease. One of the reasons this study was so successful is its unprecendented size. Pooling our resources has yielded spectacular results, which is what the participants from three continents hoped for. At the same time, this study underscores the fact that rare variants may well carry a significant part of the genetic risk of schizophrenia, so our next task is to use the ever more affordable sequencing technologies to find more of them,” said Kari Stefansson, CEO of deCODE and corresponding author on the paper.

In the first phase of the study, the deCODE-led SGENE consortium conducted a genome-wide scan of more than 300,000 SNPs in a total of 17,000 patients and controls from England, Finland, Germany, Iceland, Italy and Scotland. The 1500 SNPs with the best signal were then analysed in 11,000 patients and controls from the International Schizophrenia Consortium (ISC) and the European-American portion of the Molecular Genetics of Schizophrenia studies (MGS). Twenty-five SNPs with strong suggestive correlation were then followed up in more than 20,000 patients and controls from the Netherlands, Denmark, Germany, Hungary, Norway, Russia, Finland and Spain. Bringing together the results of different consortia established he association between the total of seven markers on chromosomes 6, 11, and 18 with increased risk of schizophrenia.

deCODE and all of the authors would like to thank the participants who took part in this study and made it possible. The SGENE consortium and its affiliated groups include deCODE genetics, the National-University Hospital in Reykjavik, the University of Aberdeen, the Ravenscraig Hospital in Greenock, the Institute of Psychiatry at King’s College London, the National Public Health Institute in Helsinki, the Ludwig Maximilians University and GlaxoSmithKline’s Genetic Research Center in Munich, the University of Copenhagen, the University of Oslo, the University of Heidelberg, the University of Bonn, the University Medical Center of Utrecht, Nijmegen Medical Center, the University of Verona, the Duke University Center for Population Genomics and Pharmacogenetics and the University of Sichuan, China. Follow up cohorts included those from Aarhus  University, the National Serum Institute, and Bispebjerg and Glostrup hospitals, Denmark; Semmelweis University, Budapest; the Mental Health Research Center of the Russian Academy of  Sciences; the Universities of Valencia and Santiago de Compostela, and the Hospital General Universitario Gregorio Marañón, Madrid, Spain; The Northern Finland Birth Cohort; Karolinska Institutet, Stockholm; Universities of Amsterdam, Utrecht and Maastricht, the Netherlands. The institutions comprising the ISC and MGS can be found in papers published concurrently with the present study in the online edition of Nature.

deCODE Discovers a Gene Linked to Risk of Kidney Stones and Osteoporosis. Findings offer promising target for drugs to better regulate calcium metabolism, are integrated into deCODEme™.

A discovery by scientists at deCODE genetics and academic colleagues from Iceland, the Netherlands and Denmark has pointed to a common biological mechanism contributing to both kidney stones and decreased bone mineral density (BMD). About 60% of the population carry two copies of a single-letter variation in the human genome (SNP) on chromosome 21, putting them at roughly 65% greater likelihood of developing kidney stones than those who carry no copies. This single variant may thus account for more than a quarter of the incidence of kidney stones, and in women carriers it is also associated with decreased BMD at the hip and spine.

The study, which involved the analysis of the genomes of some 50,000 patients and controls, is published in the online edition of Nature Genetics and will appear in upcoming print edition of the journal.

The SNP is in the gene encoding claudin 14 (CLDN14), a protein expressed in the kidney and one of a family of membrane proteins that regulate the passage of ions and small solutes between cells. As calcium is a key component both of most kidney stones and of bone, the deCODE team examined the relationship between CLDN14 and the metabolism of calcium. The results suggest that the SNP may be contributing to increased calcium excretion in urine, a major risk factor for kidney stones and also a sign of bone loss.

“This is an exciting finding because it uncovers a highly plausible common biological mechanism leading to two diseases. This offers a potentially attractive new pathway for drug discovery, and the next task is to build on our undertanding of how this SNP increases risk of these diseases and how this pathway could be targeted therapeutically to address this risk. As ever, deCODEme subscribers will see this new variant in their profiles, and we look forward building on this discovery,” said Kari Stefansson, CEO of deCODE.

About kidney stones
Kidney stones are small crystals formed of dissolved minerals, mainly calcium, that form in the kideys. Smaller stones can simply be passed through urination, though larger ones can block the urinary tract, causing considerable pain and bleeding. Kidney stones affect some 5% of women and 10% of men in the industrialized world. Larger stones can be detected with ultrasound screening and broken up to facilitate passage, though the recurrence rate is high.

deCODE would like to thank all those who participated in this study, as well as the collaborating clinicians and scientists from the Landspitali University Hospital in Reykjavik, Iceland, Radboud University Nijmegen Medical Centre in Nijmegen, Netherlands, Nordic Bioscience A/S in Herlev, Denmark and the Center for Clinical and Basic Research A/S in Ballerup, Denmark.

As a deCODEyou reader, you have an active interest in how genetics can help to improve personal health and healthcare. If you are a deCODEme subscriber or have taken one of our DNA-based diagnostic tests, you have already followed up on that interest.

Then again, you may not have had your genome analyzed yet. You may simply be interested in taking part in research, having a scan, or simply in keeping up with the latest discoveries.

But whoever you are, your genome is information about you. And at deCODE, we believe that your genome belongs to you. Over the past decade we have worked with hundreds of thousands individuals who have decided to use their genome to advance our gene discovery work, to understand their risk of a certain disease, or who want to have a broad and constantly updated look at their genome through deCODEme. In every case, we think it is the individual who has the right to decide to use their genome and learn about it as they wish.

Our job is to find the variations in the sequence of the genome that have an impact on risk of disease, and to report to those who use our tests and scans what those findings mean to them. We have done a lot of this – more than anyone else. And because we take your genome as seriously as you do, our tests and scans only detect genetic risk factors that have been validated in multiple populations and to very strict criteria. Many of the risk factors we have found and test for in diseases like heart attack, type 2 diabetes and breast cancer account for a large proportion of the occurrence of these diseases. Some have as big an impact on risk as do some of the major lifestyle and environmental risk factors that are already a standard part of risk screening.

So when we hear august voices argue that you shouldn’t have the right to look at your genome if you want to, or that we shouldn’t test for genetic risk factors until we know everything there is to know about the human genome, we feel obliged to disagree. In this week’s New England Journal of Medicine, we have heard again that it is “too early” to measure genetic risk factors for common diseases. Why? In essence because in the coming years we are likely to discover many more genetic risk factors that will help to round out our understanding of all of the risk factors that exist. To be sure, we will discover more risk variants in a great many diseases. Many will be common but with little effect on risk. Others will be rare but will confer a high likelihood of disease and thus likely be useful components in genetic tests.

But since we already know risk factors that can nearly double the risk of heart attack, diabetes or breast cancer, in a substantial portion of the population, we take the much clearer view that there is an ethical responsibility to make tests for these risk factors available as widely as possible. As our CEO, Kari Stefansson, was cited as noting in the New York Times yesterday, our tests can identify people who are at several times average risk of major diseases, and there is nothing trivial about that sort of increased risk.

After all, we believe that testing for cholesterol is a good thing, even though our understanding of just how LDL impacts risk of heart disease in incomplete. Similarly, we are only now learning how to optimize the use of statins (and that our heart attack risk factor on chromosome 9p21 has been shown to be helpful for finding the best dose for individuals). How many lives would have been lost if we had taken statins off the market until that elusive day when we thought we understood everything about them?

In our view the challenge is rather to try to bring genetic risk factors into clinical practice as swiftly as possible. As an article this week in The Times points out, a deCODEme scan has a lot of actionable risk information in it. But one of the things we need to do is educate doctors about how to use such results  and how to integrate genetic risk into everyday screening. Our own experience with doctors is that most are very eager to learn. Moreover, genetic information complements what they already do and helps them to deliver better and more personalized medicine to their patients.

In the past few years we have made rapid strides in identifying the key genetic risk factors for some of the most common diseases in our society. Very large independent studies have established that detecting these risk factors can help individuals to act to protect their health and to get the treatments that are best suited to them. This is precisely the sort of information that is going to make it possible to transform our healthcare system into one that is both more effective and efficient – focused on preventing disease and treating it early, rather than spending vast sums of money once people are already seriously ill.

You and your genome are already at the heart of this transformation. If someone tells you that you need to wait, or that they will decide whether and what you can learn about yourself, you need to set them straight. We’ll be there with you.

Dr Edward M Farmer
Chief Communications Officer
deCODE genetics Inc.

Iceland was mainly settled by Scandinavian men and women from Irealand and Scotland

In a paper published today scientists at deCODE genetics present the results of the largest study of ancient DNA from a single population ever undertaken. Analyzing mitochondrial DNA, which is passed from mother to offspring, from 68 skeletal remains from approximately 1000 years ago, the study provides the most detailed look to date at how a contemporary population differs from that of its ancestors. The results confirm previous deCODE work that used genetics to test the history of Iceland as recorded in the sagas.

Audio link:  Dr. Kari Stefansson interviewed on BBC WORLD. BBC

These studies demonstrated that the country seems indeed to have been settled by men from Scandinavia – the vikings – but that the majority of the original female inhabitants were from the coastal regions of Scotland and Ireland, areas that regularly suffered raids by vikings in the years around the settlement of Iceland 1100 years ago.

Perhaps the most remarkable finding of the study published today is that the gene pool of contemporary Icelanders appears to have evolved rapidly over the intervening thousand years. As a result, the original female settlers are genetically more closely related to the present day populations of Scotland, Ireland and Scandinavia, as well as those of northwestern Europe and even southwestern Europe, than they are to present day Icelanders. This is an important demonstration of a phenomenon known as ‘genetic drift.’ In essence, in any population certain individuals will have more offspring and, by chance and in this case over the course of 35 generations, many more descendants than others. And as a result, particularly in a small population, the genetic variety of the original population can decrease and change over time. In this study only mitochondrial DNA was studied, but the same phenomenon applies to the Y chromosome, which is passed from fathers to sons, and to any other part of the genome. The paper, ‘Sequences from first settlers reveal rapid evolution in Icelandic mtDNA pool,’ is published today in the open-access journal PLOS Genetics.

“This study is a major contribution to the use of ancient DNA studies in tracing the history not just of single populations, but of our species and how we spread from Africa to every corner of the globe. It is the first such study to be large enough to permit meaningful statistical methods to be applied to ancient DNA. We very much hope this will aid and encourage others to follow with large studies in other parts of the world. In this field, as in the genetics of common diseases, we are pleased and proud to be able to put the knowledge we gain in Iceland to work for the benefit of people everywhere,” said Kari Stefansson, CEO of deCODE.

deCODE scientists have discovered new genetic variants influencing BMI, weight and risk of obesity

As we all know to well, for decades the scales have been tipping in favor of obesity. The epidemic of obesity in many industrialized countries has been driven by many factors, including easy access to fast food, an increasingly sedentary lifestyle, insufficient daily physical activity. All of this while our genomes have evolved on a background of scarcity, often putting a premium on the ability of the body to turn food into fat and store energy for leaner times. A paper published today by deCODE scientists and academic colleagues from the US and Europe provide a significant advance in our knowledge of the underlying genetics and biology of obesity, providing new information for understanding and addressing obesity and perhaps nudging the scales the other way.
In a major study published today, the deCODE-led team reports the discovery of a large number of single-letter variations in the sequence of the human genome (SNPs) influencing body weight, body mass index (BMI) and risk of obesity. (BMI>30kg/m2). The discoveries were made be scanning over 300,000 SNPs in more than  30,000 individuals from Iceland, The Netherlands, and the United States, and then confirming the findings in individuals from Denmark and the multinational GIANT consortium, totaling close to 40,000 individuals. Interestingly, many of the variants discovered are located near genes related to energy sensing or food intake regulation in the brain, suggesting its importance in the development of obesity.   Although these variants only explain a small fraction of the variation in BMI, they provide new insght into the basic mechanisms underlying obesity and a first step towards identifying drug targets that can be used to address the global public health challenge of obesity.

A new genetic test assessing a woman's risk of developing the most common forms of breast cancer has arrived. Can the test, developed by the biopharmaceutical company deCODE, improve the way doctors screen for breast cancer?

Breast cancer kills 40,000 people a year in the U.S. This is about the population of Atlantic City, New Jersey. Imagine, each year an entire city wiped out by breast cancer.

To help fight breast cancer, a new test assessing individual risk has just become available. For women without a clear family history of the disease, the deCODE BreastCancer^TM test assesses their personal risk of developing the most common forms of breast cancer. The DNA test, launched by the biopharmaceutical company deCODE, makes it possible to identify those women at significantly higher than average risk, helping doctors use new screening technologies and treatments in a more targeted, personalized and effective manner.

The key to fighting breast cancer, like all cancers, is early detection, which is why the medical field is buzzing over deCODE’s new breast cancer test.

“This test helps define individual prevention which is what so many of my patients want,” says Owen Winsett, MD, founder and director of the Breast Center of Austin.

Dr. Winsett, who has already ordered the test for 25 of his patients, can’t hide his enthusiasm over how the decode breast cancer test is changing the way he screens for the disease.

“I’m excited to be able to extend my screening and prevention practice. I plan to make this test a standard tool for helping me decide which of my patients may benefit from screening at an earlier age, or benefit from more intensive screening, including breast MRI’s. And then if my patients don’t have breast cancer, to motivate them to begin healthy preventive strategies.”

The test is not offered directly to individual women, but rather ordered by doctors on the request of their patients. deCODE advises that the test-which scans a woman’s genome for seven widely replicated single-letter variations (SNPs) in the human genome that are linked to increased risk of breast cancer-is a way to better connect doctor and patient.

Dr. Winsett agrees. He recommends that before taking this test women should consult their general practitioner, and if their doctor is uncertain about how to use the results of the test, to seek out a breast cancer specialist.

Like all new technologies – particularly those that may change accepted clinical practice – this type of risk screening has raised concerns in some quarters. Some critics have argued that the test is not accurate enough because it’s not based on a large enough sample of women to predict risk of breast cancer. However, the evidence tells a different story. According to Dr. Winsett, epidemiological studies on breast cancer present a fairly straightforward argument that deCODE’s genetic test does indeed give a picture of a patient’s baseline risk. The evidence shows that the seven SNPs in the human genome that the decode test scans for are linked to an estimated 60 percent of all breast cancer cases. These findings are derived from integrated data from discovery and replication studies published in major peer-reviewed journals and involving nearly 100,000 breast cancer patients.

“I remind patients this test is one peice of the puzzle,” says Dr. Winsett. “The test won’t tell patients if they will get breast cancer or if they won’t. It shows the average risk, and then says where a woman stands in relation to that average and then what her absolute risk is. As a doctor, deCODE’s breast cancer test helps me evaluate a patient and make a future plan for prevention and testing.”

Still, some non-clinicians feel genetic testing only benefits women who have a strong family history of breast cancer. One bioethicist recently wrote on an MSNBC blog that “the tests Decode and other companies are offering are more likely to empty family pocketbooks and leave women with a false sense of security than they are to prevent breast cancer.”

Dr. Winsett finds this argument muddled. There are already tests to pick up genetic risk factors for highly familial forms of the disease, and neither those tests nor deCODE’s for measuring risk will cure or prevent breast cancer. Dr. Winsett notes that mammograms, ultrasounds and breast MRIs don’t prevent women from getting breast cancer either, but doctors still use them because they are tools to help detect breast cancer.

“Sometimes a patient will say, ‘I’ve had a mammogram regularly, so how can I get breast cancer?’ It’s easy to think that. But neither mammograms nor the deCODE test can on their own prevent breast cancer. It’s how you use the information from the genetic test to shape a patient’s care that leads to prevention or early detection.”

Genetic risk screening for breast cancer might sound like cutting-edge medicine, but doctors have been using genetics to assess risk of developing breast cancer for years. There are genetic tests that look for mutations of the BRCA 1 and BRCA 2 genes. Variations in these genes are linked to the rare and essentially purely genetic forms of breast cancer.

While detecting the BRCA variants is considered very valuable information to women with a family history of the disease, doctors and researchers knew genetics would one day play a bigger role in the remaining 95 percent of breast cancers. The deCODE BreastCancer^TM test is aimed squarely at filling this gap, and to broadening the use of genetics in fight against breast cancer.

When a woman’s genome is scanned with deCODE BreastCancer, deCODE’s CLIA-registered laboratory checks for certain versions of seven single-letter variations in the genome, called SNPs. According to which versions are detected, that woman’s risk is then tallied, adding together the risk of each of the seven SNPs, to yield a score in relation to average risk, which is about 12% for American women of European origin. By multiplying the relative risk by the average, the results also provide a score of a woman’s absolute risk of developing breast cancer in her lifetime.

Depending upon a woman’s assessed risk, her doctor may suggest that she receive regular mammograms earlier than age 40, the standard starting age in the United States. If the test reveals a high risk, clinicians like Dr. Winsett might order a more advanced breast MRI or an ultrasound test for his patient. In some cases, high-risk patients with other contributing risk factors might start on a course of treatment to reduce the risk of tumors.

Decode’s breast cancer test is not a silver bullet. It won’t cure cancer. It measures risk and will be used in conjunction with other diagnostic tools and treatments to reduce the impact of the disease. But by using deCODE’s genetic test to find out which patients have a higher risk for the disease, says Dr. Winsett, earlier detection of breast cancer is possible.

“With the advent of deCODE’s breast cancer test we can intervene before the cancer happens. My hope is that we’ll see fewer breast cancers. I’m in business of dealing with breast lumps. I’m hoping this test can help reduce the breast lumps that I see.”

Scientists at deCODE genetics Genetic Service Facility lab in Iceland

The number of companies offering genetic tests to the public is large and growing. But there are vast and very real differences in the quality, purpose and price of testing services out there. So how do you tell the difference between them? And how do you decide which to use?

Knowing what you want

First and foremost, you need to think about what sort of information you hope to gain from your genome and how accurate you want the results to be. Are you taking the test only for fun, perhaps hoping to talk about your results on Facebook? Or are you interested in using it to protect or improve your health, perhaps working with a doctor? And do you want your information to be kept strictly private so that you are in full control of those with whom you share it, or are you comfortable with others being able to access it and use it?

At deCODE, we have studied the genomes of hundreds of thousands of people over the past twelve years. Our goal has been to discover what variations in the human genome give some people higher or lower than average likelihood of developing many of the most common diseases in our society. We use that information to develop products like genetic tests that can help people to stay as healthy as possible for as long as possible. From day one that’s been our bread and butter – it’s not an idea that occurred to us last week or even last year.

And with that experience, and having worked with so many people, there are a few basic things that we think you should look for in any genetic testing service. These are fundamental characteristics that we demand of ourselves in all of our discovery work, and we think you should settle for nothing less.

Buyer’s checklist

In any field, in order to offer services to the public you have to be able to stand behind the quality of your product. In genetic testing, the basis of any test worth paying for is good science: large-scale studies that establish and then replicate in independent groups links between specific markers in the genome and specific traits, such as diseases. Making those links requires gathering large sets of very high quality, consistent data. It requires teams of doctors, geneticists and other scientists, as well as certified DNA analysis laboratories, statistical tools and computing power and software to accurately analyze the datasets. If you can do all this under the strictest data and privacy protection protocols in the world, you will reward the participation of your research subjects with peace of mind they deserve.

That’s just for starters. In order to offer a test, you need to be give your customers the same certified quality of DNA analysis, as well as the ability to accurately interpret what the findings of large studies mean for disease risk. In short, you need all the same capabilities and expertise as for research, but focused on accurately and securely delivering results to individuals.

The gold standard

These are the standards that lie behind deCODEme and all our diagnostic tests. We offer the best science, usually our own, as our scientists lead the world in finding genetic risk factors for common diseases. Where we do use discoveries made by others, our scientists have validated the findings according to our own rigorous criteria. We have our own CLIA-certified DNA analysis laboratory, one of the largest of its kind in the world, and do our own quality control. We share your results with no one but those you specifically request. We offer our customers the ability to check whether they carry validated risk factors for dozens of diseases, and update their profiles rapidly and regularly as new discoveries are made. This isn’t trivial stuff, and our prices reflect the quality of the products we offer.

Don’t just take our word for it: the value of deCODE tests is reflected most clearly in the stories of customers like you. On this blog you can read about what they have to say about how they are using their results to better look after their own health.

Your genome, your choice

This is a high bar, and one that few others will pass. Can you find cheaper services out there? Yes. Are there dot-com storefronts that outsource the science and the analysis of your genome? Yes. That are focused less on quality and more on website bells-and-whistles for using your genome for social networking? Yes again.

But your genome is yours, and we think you have a right to choose the best for yourself if that’s what you want. At deCODE we are not offering cut-rate services, outsourcing the analysis of your genome, or cutting corners on privacy protection. We give you a portal into the best and latest in genetics, offering the highest quality services available for those who want to know how the latest breakthroughs in human genetics can be used to improve their health and healthcare. If that’s you, we encourage you to check how other services stack up to deCODE – and we look forward to hearing from you!

Urinary bladder cancer is something many people have never heard of. But it is the sixth most common form of cancer in the United States, and its environmental risk factors include exposure to toxic chemicals, including some used in industrial processing as well as cigarette smoke. Genetic factors also play a role and may help to elucidate how bladder cancer starts and develops.

Today, deCODE’s cancer group and colleagues at Radboud University in the Netherlands report the discovery of two single letter variants (commonly referred to as SNPs) in the human genome that confer increased risk of bladder cancer. Both are common, and 20 percent of people of European descent carry two copies of the highest impact SNP, located on chromosome 8q24. That puts them at about 50 percent higher likelihood of developing bladder cancer than people who do not carry the variant.

Since risk screening for bladder cancer has been largely confined to those with known exposure to carcinogenic substances, the ability to test for these variants may useful particularly for those know to have other risk factors. As with all our discoveries, we have worked hard to publish them and to secure intellectual property rights to enable us to put these findings straight to use. deCODE has integrated these findings into deCODEme, so that individuals and their doctors can utilize these findings if it is warranted.

Another intriguing aspect of the paper published today in Nature Genetics is that over the past year deCODE and others have linked SNPs on the same stretch of chromosome 8 to risk of prostate, breast and colorectal cancer. We are looking into what common processes may be triggered or affected by these variants, since a common mechanism might be able to tell us something about the underlying molecular causes of cancer in general.

Official deCODE Genetics Press Release:

Contacts:
Edward Farmer Gisli Arnason
+1 646 417 4555 +354 570 1825
edward.farmer@decode.is gisli.arnason@decode.is

deCODE and Radboud University Discover Common Variants in the Human Genome Conferring Risk of Bladder Cancer

Detection may be used to complement and target screening for the disease; findings will be integrated into the deCODEme™ personal genome scan.

Reykjavik, ICELAND, September 14, 2008 – Scientists at deCODE genetics (Nasdaq:DCGN) and colleagues at Radboud University Medical Center in the Netherlands today report the discovery of two common single-letter variants in the human genome (SNPs) that confer increased risk of urinary bladder cancer. Approximately 20% of people of European descent carry two copies of the first variant, a version of a SNP on chromosome 8q24, putting them at a 50% higher risk of developing bladder cancer than those without the variant. Individuals who carry two copies of a common version of another SNP on chromosome 3 were found to be at a 40% higher risk of the disease than non-carriers. These are the best-replicated genetic variants ever linked to bladder cancer risk, and the study analysed genotypic data from more than 40,000 patients and controls from Iceland, the Netherlands and eight other European countries. The paper, entitled ‘Sequence variant on 8q24 confers susceptibility to urinary bladder cancer,’ will appear today in the online edition of Nature Genetics at www.nature.com/ng.

“In all cancers, the ability to identify individuals at high risk, screening them intensively and intervening early, is the key to improving prevention and outcomes. We expect that the detection of these and other risk variants will soon be employed to complement the assessment of standard risk factors for bladder cancer. As with all of our discovery work, we seek to publish our findings and establish a solid intellectual property position in order to bring these swiftly into the healthcare arena, and have already folded today’s findings into our deCODEme™ personal genome analysis service. At the same time, we are working to identify the common thread of variants we and others have discovered on chromosome 8q24 that confer risk of several forms of cancer, including prostate, breast, colorectal and now bladder. If a common molecular mechanism exists, it could provide an important insight into oncogenesis more broadly,” said Kari Stefansson, CEO of deCODE.

For a more detailed discussion of today’s findings you can watch a video discussion between Dr. Stefansson and Dr. Simon Stacey on our blog, at www.decodeyou.com.

Urinary bladder cancer is the sixth most common type of cancer in the United States. It is estimated that 68,810 individuals will be diagnosed with bladder cancer in the United States during 2008 and that 14,100 people will die of the disease. Bladder cancer has been linked to exposure to various types of toxic substances such as cigarette smoke and industrial chemicals. Although it has been known for some time that genetic factors also play a significant role, identifying validated genetic risk variants had been problematic. Incidence of bladder cancer varies considerably between ethnicities, and as the risk factors reported here were discovered by analysing DNA from groups of European descent, it is our hope that the publication of these findings will contribute to the swift analysis of the impact of these variants in cohorts of other continental ancestries.

The authors wish to thank the thousands of patients and control subjects who participated in this study, and acknowledge the assistance of national cancer registries that worked to identify potential participants. Data and sample collection in Iceland and the Netherlands was funded in part by European commission grants LSHC-CT-2005-018827 and LSHM-CT-2004-005166.

About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of diagnostics and drugs for common diseases. deCODE is a global leader in gene discovery — our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. Through its CLIA-registered laboratory, deCODE is offering a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProCa™ for prostate cancer; and deCODE Glaucoma™ for a major type of glaucoma. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com; on our diagnostics site at www.decodediagnostics.com; for our pioneering personal genome analysis service, at www.decodeme.com; and on our blog at www.decodeyou.com.

Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results, and the timing of events, to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, those relating to our ability to obtain financing and to form collaborative relationships, uncertainty regarding potential future deterioration in the market for auction rate securities which could result in additional permanent impairment charges, our ability to develop and market diagnostic products, the level of third party reimbursement for our products, risks related to preclinical and clinical development of pharmaceutical products, including the identification of compounds and the completion of clinical trials, the effect of government regulation and the regulatory approval processes, market acceptance, our ability to obtain and protect intellectual property rights for our products, dependence on collaborative relationships, the effect of competitive products, industry trends and other risks identified in deCODE’s filings with the Securities and Exchange Commission, including, without limitation, the risk factors identified in our most recent Annual Report on Form 10-K and any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.

Here are a few thoughts on Nic Fleming’s piece on personal genome scans, of which one was our own, deCODEme:

Our genomes are all remarkably similar. And so it is the differences that are most interesting and important, and that make us who we are.

The same can be said of genetic testing services. We at deCODE were not at all surprised that Mr. Fleming found that he got some varying results from the three genome scans that he tried. Indeed we would be surprised (and more than a little dismayed) if he hadn’t. Analyzing the genome – accurately detecting which genetic markers individuals have at specific points in the genome, and correlating these variations with risk of a range of common diseases – has been our bread and butter for well over a decade. With the analysis of hundreds of thousands of genomes under our belt, we can say with some authority that it is not a trivial business. We would never ourselves rely on consultants to tell us what variants to look for, what they mean, or to oversee the genotypic analysis itself. And we certainly would not offer such treatment to doctors or members of the public.

That said, it would be a strange logic that therefore suggests that the whole field, or the very well validated science that now exists linking specific markers to risk of common diseases, should be lumped in together as though all are nothing but dot-com storefronts selling DNA analysis today where they might have been selling sofas last year. deCODEme or our diagnostic tests, for example, only detect risk variants that meet exacting criteria: they must have been published in peer-reviewed scientific journals and replicated in large cohorts from several populations. Many genetic risk factors for common diseases have passed this high bar, and have thus been as well validated, as most non-genetic risk factors were when they were first brought into clinical use. As Mr. Fleming notes, there are physicians who are incorporating genetic risk factors into their clinical practice and with some important successes that individuals have been willing to share with the world. (We are posting some of these stories on this blog and on the personal stories page of deCODEme).

So, as suggested by Mr. Fleming’s piece and by Lord Taverne and others he interviewed, it is of pressing importance to establish high scientific and technical standards and regulations for such tests. We therefore hope that the Human Genetics Commission, and other oversight bodies in Europe, the US, and elsewhere will continue to scrutinize how best to provide an effective sheriff for this new territory. Doing so will enable individuals and the healthcare system to take full benefit from the potential of this new technology, while protecting the public from unscrupulous cowboys. At the least – since some people like cavorting with fun-loving bandit types – everyone would know who was who.

Edward Farmer
Chief Communications Officer
deCODE genetics

deCODE and SGENE Consortium Discover Deletions in the Human Genome Linked to Risk of Schizophrenia

Findings may provide the foundation for a test to complement standard clinical diagnosis, potentially enabling earlier intervention and treatment

A team of scientists led by deCODE genetics has discovered evidence of three rare deletions in the human genome that confer a greater risk of schizophrenia. This discovery shows that individuals who have one of these deletions may be up to 15 times more likely to develop schizophrenia than the population at large. See “Large recurrent microdeletions associated with schizophrenia” which appeared this afternoon in Nature (www.nature.com)

“Schizophrenia is a disorder affecting thoughts and emotions. It is therefore a quintessentially human disease, but one that is little understood biologically and which is difficult to diagnose. These findings are important because they shed light on its causes and provide a first component to a molecular test to aid in clinical diagnosis and intervention. These discoveries also demonstrate one way in which we can use SNP-chips to find rarer genetic factors conferring risk of disease. In many disease areas we have had great success of late in identifying what these chips are best suited to find: common variants conferring relatively modest increases in risk. But we know that individuals with certain mental disorders such as schizophrenia tend to have few children, and thus that we may have to identify a larger number of rare but high risk variants to understand the genetic contribution to susceptibility. It is encouraging that our efforts to use SNP chips to detect rarer variations such as spontaneous deletions and duplications is now bearing fruit,” said Kari Stefansson, CEO of deCODE.

In the recent wave of discoveries of risk variants for common diseases, those associated with mental disorders such as schizophrenia, autism and others have been conspicuously absent. This phenomenon, and the fact that people with these disorders tend to have few children, suggest that rarer and perhaps spontaneously generated variants may account for a greater proportion of the disease burden in these conditions than in others. SNP-chips are not well suited to finding rare SNPs but can, with sufficiently large sample sizes, be used to identify deletions and duplications – known as copy number variations, or CNVs – which can also be carried by healthy individuals in one generation and contribute to risk of disease in the next.

In its work on the inherited components of dozens of common diseases, deCODE has discovered gene variants that significantly affect individual susceptibility or protection against disease. In the common forms of these conditions – such as obesity, type 2 diabetes and cardiovascular diseases – deCODE has previously shown that genetic variants confer increased or decreased risk by up-regulating or down-regulating the activity of major biological pathways.

In today’s paper, the deCODE team and collaborators from Merck demonstrate one of the principal ways in which the activity of biological pathways is functionally perturbed in a quintessentially complex condition: obesity.

Kari Stefansson, CEO of deCODE, put the study into context: “One of the observations we have made in our work on the isolation of disease genes is that the genetic risk of common diseases is often conferred by variations in the sequence of the genome that affect expression of genes. Hence, one of the ways to approach the study of common diseases is through the analysis of gene expression. This paper provides a substantial contribution towards the understanding of gene expression in man and one example of how it can be used to expand our knowledge of one disease, namely obesity.”