deCODE genetics ehf today emerged as a newly financed, private company focused on advancing the science of human genetics and its application to products and services that improve human health. The new company will be building on the scientific leadership in genetics it developed over more than a decade as a subsidiary of deCODE genetics, Inc. deCODE ehf was this week purchased from its former parent company by Saga Investments LLC, a consortium that includes Polaris Ventures and ARCH Venture Partners, two leading life science investors. deCODE will continue all of its operations and product lines in this field, including its deCODE diagnostics disease risk tests; deCODEme™ personal genome scans; and contract service offerings including genotyping, sequencing and data analysis. Going forward, deCODE  will concentrate on translating its science into medically and commercially important products and services.  The company will be led by a two-man executive committee comprised of Earl “Duke” Collier, previously an executive vice president at Genzyme Corp.,who will serve as CEO, and Kari Stefansson, who will serve as executive chairman and president of research.

deCODE operates the most productive human gene discovery engine in the world. It is driven by genetic and medical data from 500,000 participants from around the globe taking part in its gene discovery work; comprehensive genealogies linking the 140,000 Icelandic participants; a major CLIA- and CAP-certified genotyping and sequencing facility; and statistical and informatics tools for mining large datasets, for maximizing the information derived from genotyping and sequencing data, and for visualizing genetic and disease data in research, in the clinic, and for subscribers to its genome scans.

“deCODE has led the world in discovering variants in the sequence of the human genome that affect the risk of common diseases. Our resources and expertise have also enabled us to develop the leading analytical tools in the field, and we are putting all of this to work to provide unique value for patients, physicians and researchers. As we enter the era of sequencing entire genomes, we believe our ability to make sense of ever larger amounts of data will continue to keep us in the lead in discovery. And with our now solid financial backing and the splendid addition of Duke Collier to our management, we will be taking a lead in the translation of our science into powerful products and services.” said Kari Stefansson.

“I am pleased to be joining Kari and the outstanding scientific team at deCODE,” said Duke Collier. “deCODE combines world class science devoted to human genetics, unmatched access to genetic data, and a powerful set of tools for managing and analyzing this data. SNP genotyping, and now genomic sequencing, is taking human genetics into an ever expanding world of research, discovery and translation. With its scientific skill and industrial scale analytical capacity, deCODE will be an invaluable partner to investigators, labs and companies working at the highest levels of sophistication in this exciting field. I am thrilled by the challenge and the opportunity.”

deCODE scientists have discovered a single SNP that confers increased risk if inherited from the father, but is protective if inherited from the mother

Scientists at deCODE genetics, Inc. publish in the journal Nature the discovery of a version of a common single-letter variant in the sequence of the human genome (SNP) with a major impact on susceptibility to type 2 diabetes (T2D). The impact of the T2D variant is not only large, but unusual: if an individual inherits it from their father, the variant increases risk of T2D by more than 30% compared to those who inherit the non T2D-linked version; if inherited maternally, the variant  lowers risk by more than 10% compared to the non T2D-linked version. Nearly one quarter of those studied have the highest risk combination of the versions of this SNP, putting them at a roughly 50% greater lifetime risk of T2D than the quarter with the protective combination. This is the second largest effect of any genetic variant for T2D apart from SNPs in TCF7L2, discovered by deCODE in 2006.

“We could make this discovery beacause we are in the unique position of being able to distinguish what is inherited from the mother from what is inherited from the father. This we can do because of the large amount of data we have assembled on the Icelandic population. These data empower us in many ways. For example, using our ability to impute sequence data, we can multiply by 100 times the amount of information generated by sequencing one individual. We can use these tools to discover and integrate rarer variants into our tests and scans, identify drug targets for licensing, and put our know-how at the disposal of our service customers. We believe that this is an important advantage for conducting large-scale whole sequence studies over the next couple of years,” said Kari Stefansson, CEO of deCODE.

Because the risk is inherited and varies in this way, the SNP, located on chromsome 11, had never been linked to T2D even though it had been genotyped in large, traditional genome-wide association studies (GWAS). These do not distinguish between paternally and maternally inherited SNPs. But deCODE can track the parental origin of virtually any SNP in the genome of the tens of thousands of Icelandic participants in the company’s gene discovery work. In this study, deCODE used its population-wide genealogy database and proprietary statistical tools to determine the parent of origin of a number of SNPs in some 40,000 Icelandic participants in the company’s gene discovery programs. Some of these SNPs had previously been associated with different diseases and are located near “imprinted” genes – genes in which only the maternally or paternally inherited copy is “switched-on” to encode a protein. Five of these, one each in breast and skin cancer and three in T2D, showed that the parental origin of the variants affects the risk they confer.

The paper, “Parental origin of sequence variants associated with complex diseases,” is published online at www.nature.com, and will appear in the December 17 print edition.

As a follower of deCodeYou, we wanted to let you know about some important developments in the company and how we believe these will underpin our ability to continue to keep you in the forefront of understanding what the latest advances in genetics mean for you and your health.

For the past several months, deCODE has been working on restructuring its operations. As a result of these efforts, deCODE has entered into and filed concurrently with its Chapter 11 petition announced today an asset purchase agreement under which it would sell its Iceland-based human genetics operation to new owners. This is the subsidiary that conducts our human genetics research, manages our population genetics resources and provides our personal genome scans and DNA-based risk assessment tests. This agreement is subject to a number of contingencies, including a competitive bidding procedure and court approval in accordance with bankruptcy law. It also provides interim financing to enable us to continue operations during the Chapter 11 process, and we have asked the court for the customary authority to continue to provide products and services to our customers without interruption during the bankruptcy process.

Thus you should expect to continue to hear from here on all the latest in human genetics and its relevance to health and healthcare. You can read our press release here.

With best regards,

The deCODEyou team

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 Discovers Second Common Genetic Risk Factor for Atrial Fibrillation and Stroke. Will be integrated into deCODE AF™ DNA-based risk assessment test, and into the deCODEme™ and deCODEme Cardio™ scans.

Scientists at deCODE genetics and colleagues from Europe and the United States today report the discovery of a common single-letter variant in the sequence of the human genome (SNP) conferring increased risk of atrial fibrillation (AF) and stroke. The findings will be integrated directly into the deCODE AF™ reference laboratory test for gauging individual risk of AF and stroke and helping to identify stroke patients who may benefit from enhanced monitoring for AF. The study is published online today in Nature Genetics.

The new SNP is in the ZFHX3 gene on chromosome 16q22, and the more than one third of people of European descent who carry one copy are at approximately 20% greater risk of AF and cardioembolic stroke than are individuals who carry none. AF is the most common type of cardiac arrhythmia, and is a major risk factor for stroke. Because AF is often intermittent and difficult to detect, gauging genetic susceptibility can help doctors to decide which of their stroke patients might benefit from longer-term monitoring for AF following a stroke. Those with stroke due to AF may be given different therapy than they would otherwise. This is the purpose of deCODE AF™, at the heart of which is the major AF and stroke variant discovered by deCODE on 4q25. Indeed today’s findings are the result of deCODE’s program to build on this work and to find new risk variants. After expanding their genome-wide association study in Iceland, the deCODE team took the top SNPs outside the 4q25 region and typed them in case-control cohorts from Iceland, Norway and the United States. This confirmed the ZFHX3 SNP as a risk variant for AF. Analysis in stroke cohorts from Iceland, Germany, Sweden and the UK demonstrated that this SNP was associated with increased risk of stroke, particularly cardioembolic stroke.

“This is an important discovery and all the more gratifying because we can integrate it straight into a test that is already helping to improve patient care in the clinic.
As with our 4q25 variant, this latest discovery has been replicated in numerous populations by us and others, and the connection to cardioembolic stroke is yet further evidence that we are putting our finger on an important pathway involved in AF and stroke risk. The ability to routinely test for these risk factors means that we can understand whom we should screen intensively for AF and then prescribe the drugs most suited to the cause of a particular patient’s disease. This is the sort of personalized medicine that genetics is enabling – individualized care that may mean not only better outcomes but significant potential savings to the healthcare system. Discoveries like this are the foundation upon which this transformation is being made,” said Kari Stefansson, CEO of deCODE.

deCODE and the authors wish to thank the participants who took part in this study and made it possible. Financial support for this study was provided by US National Institutes of Health grants HL075266 and U01 HL65962 and American Heart Association grant 0940116N; by the German Federal Ministry of Education and Research (01GI9909/3), by the German Migraine & Headache Society (DMKG), and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster.

Click on the image to watch the 60 Minutes Australia segment on genetic testing

The Killer In You

60 Minutes Australia recently visited the deCODE genetics labs in Iceland and interviewed deCODE’s CEO Dr. Kari Stefansson. Among the people who did the deCODEme genetic test were journalist Liz Hayes, world surfing champion Layne Beachley and Australian television’s favorite builder, Scott Cam. To watch the 60 Minutes Australia segment click on the image above. To read the transcript of the webchat with Professor Bob Williamson click here. To learn more about deCODEme genetic tests and order your personal genome scan visit www.decodeme.com.

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.

Crown Prince Frederik of Denmark and Crown Princess Marie of Denmark along with deCODE scientist Unnur Thorsteinsdottir during an official visit to deCODE laboratories earlier this year.

Reykjavik, ICELAND, December 8, 2008 – deCODE genetics (Nasdaq:DCGN) today announced the discovery by an international consortium of scientists from deCODE and major European and US academic institutions of a single letter variation in the human genome (SNP) that is associated with increased fasting glucose levels and risk of type 2 diabetes (T2D). deCODE will employ its CLIA-registered genotyping laboratory and existing testing platform to swiftly integrate the finding into its deCODEme™ personal genome scan, and to assess the addition of this new variant to the company’s deCODE T2™ reference laboratory test for assessing individual risk of type 2 diabetes.

The multinational study analyzed a number of SNPs that had been suggestively linked with fasting glucose levels in several major studies involving some 36,000 individuals from Europe and the United States.The analysis identified a version of single SNP within the gene encoding melatonin receptor IB (MTNR1B) that was associated with notable increase in fasting glucose levels. The deCODE team then demonstrated in its Icelandic cohort that this SNP also associated with an increased risk of T2D, a finding that was then replicated in a meta-analysis of data from more than 80,000 cases and controls from Europe and the US. Approximately 10% of the participants in this study carry two copies of the at-risk version of this SNP, putting them at more than 15 percent greater risk of type 2 diabetes than individuals who carry no copies. The paper, entitled “Variants in MTNR1B influence fasting glucose levels,” is published today in the online edition of Nature Genetics, and will appear in an upcoming print edition of the journal.

“This finding is another step towards rounding out our understanding of the genetic factors that underpin glucose regulation and risk of type 2 diabetes. This variant does not confer sufficient risk to be of clinical utility on its own. But when measured in addition to our TCF7L2 variant that is the anchor of the deCODE T2™ test, it may, like other common variants conferring modest risk, enable the test to capture an even larger proportion of inherited risk. We are currently evaluating its integration into deCODE T2™, because understanding genetic risk of T2D enables individuals and their physicians to focus, personalize and improve prevention. In the meantime, we will be enabling our deCODEme subscribers to check their profiles for this new variant, keeping them at the cutting edge of human genetics” said Kari Stefansson, CEO of deCODE.

Type 2 diabetes: A major public health problem
T2D is a chronic condition that develops when the body either becomes resistant to or doesn’t secrete enough insulin. Diabetes affects nearly 200 million people worldwide and, according to the American Diabetes Association, some 21 million in the United States. The vast majority of these have T2D, and as many as one third of Americans with diabetes may not even be aware that they have the disease. More than 50 million Americans have pre-diabetes, a condition characterized by elevated blood glucose levels and which puts these individuals at high risk for developing T2D. T2D can be managed and – most importantly – prevented. If losing weight, eating better and getting adequate exercise aren’t enough, there are also medications that can help to manage blood sugar levels and insulin response to reduce the likelihood of developing diabetes. For more information on T2D and how to prevent it, you can go to the American Diabetes Association’s website.

deCODE customer rep Larus Jon Gudmundsson and genetic counselor Kris Kristjansson MD

Tapping the vast resources of deCODEme scientists

The users of deCODEme show great interest in their results and are not afraid to ask questions. deCODEme customer support welcomes all questions and inquiries and taps the vast knowledge base and resources of its research teams to respond to all emails as comprehensively and quickly as possible. Among the more general questions we receive is the following.

Question
“I’m seriously thinking about doing the DNA test. Now I only have to decide from which company. How does your test compare with tests from other companies?”

Response
There are a few key differences between the services of deCODEme and its competitors.
deCODEme is provided by a company called deCODE genetics. Scientists at deCODE genetics have been carrying out research on human genetics for over a decade and have already produced a very large portion of validated discoveries of variations in the human genome that confer risk for common diseases. Our mission at deCODE genetics is to use genetics to help people to improve their health, and one of the ways we do that is by offering the deCODEme service. The same scientists, statisticians and geneticists who actually discovered the genes engaged in making that information useful to the public. At the same time they are continue to publish the results in the best scientific journals and have been doing so many years. Now, additionally, they simultaneously make those articles available on the deCODEme customer’s profiles.

However, it is also important to note that not only do we use our own internal expertise to develop our products, process your sample and analyze the resulting data , but we also give you direct access to this expertise, should you have any clinical or scientific questions. Our clinical support team includes an MD medical geneticist and genetic counselors that you will have access to at no extra cost. In contrast, most other companies offering DNA analysis are only acting middle-men and have to outsource much of the sample processing.

Another key difference is that the deCODEme analysis consists of information on 1 million markers, while our can only offer less than two thirds of that total. This means that if you have a deCODEme profile we can provide you with higher coverage now and significantly higher quality analysis of future research findings as we make new discoveries.

Our strategy is to offer a product that is as good and as useful as possible, which is how we provide real and long-term value to deCODEme customers. We have posted an entry on this subject on our blog.

The results are presented in a simple and clear format.
deCODEme provides a report on your sample on the www.decodeme.com website that you can unlock with your password. The report will contain your actual genotypes for the SNPs in question. Additionally, you will be provided with the raw data of the complete scan, i.e. about 1 million SNP genotypes. Reference to published scientific findings relevant to your results are also a part of the report, and are individually linked to each marker that is analyzed.

The report contains a disclaimer that although a SNP is individually associated with disease risk in deCODE´s own population studies, deCODE cannot predict how that SNP will interact with variants at other SNPs in any particular person.

There is a Site Tour available now on the website under “What is deCODEme” on our website. In addition there is a FAQ (frequently asked questions) section on the website.

The deCODEme browser.
We have recently introduced the deCODEme Genome Browser, a highly sophisticated on-site tool that enables to explore your results in detail. The Genome Browser is accessible on on the deCODEme website.

Best regards,

deCODEme customer support.

deCODEme genetic test includes an identification of the male pattern baldness trait.

A team of scientists, led by Professor Tim Spector of King’s College, London, have been taking a closer look at the genetic coordinates for male pattern baldness or androgenic alopecia. Male pattern baldness is the most common form of hair loss in men and one that increases steadily with age. While it has been known for some time that men inherit a tendency for baldness via their x chromosomes from their maternal grandfather, this new research has identified a region on chromosome 20 (20p11) that suggests that a susceptibility for baldness is also inherited directly from one’s father. There is no preventative treatment as such–at least none that is guaranteed to work–but if you are among the 14% who are in the greatest risk group there’s more hope now the genetic causes of baldness are being identified. Frank Geller from deCODE genetics is among the geneticists who took part in the research. The genetic scan deCODEme already includes an identification of the male pattern baldness trait.

• Link: “Male-pattern baldness susceptibility locus at 20p11″ in Nature Genetics
• Link: “Genetic test can forecast bald facts about each man’s future” in The Times
• Link: “Hair loss now predictable with gene scan” in The National Business Review
• Link: “One-two gene punch raises odds of baldness in men” at CNN.com

On October 8th MSNBC published an article by Arthur Caplan, Ph.D. on genetic tests for breast cancer.
The following is a response by Jeff Gulcher, M.D., Ph.D, Chief Scientific Officer at deCODE Genetics.

Arthur Caplan stresses caution in the application of the new genetic risk tests for common diseases and I certainly agree that genetic testing should be applied with care. However, he goes too far when he says that the new deCODE BreastCancer genetic risk test is only useful for women who have two or more close relatives with breast cancer, is not based on large enough studies to be accurate, and is not regulated.

There are two major types of breast cancer: the rare, early onset form that occurs in certain families and for the detection (for which the Myriad Genetic test is well suited), and the common form which accounts for 95 percent of breast cancer. The vast majority of women who develop breast cancer do not have the conventional risk factors of family history, pregnancy history or breast density. Unfortunately, many of these women were likely considered to be of average risk before their cancer was found. Therefore, they were not even offered screening with breast MRI which detects two to three times more cancer at an earlier stage than mammography alone, or preventive measures such as tamoxifen treatment which can cut down cancer rates by 40 to 50%.
To date, the healthcare system has not been as good as it would like to be at predicting which women are at higher risk of the common forms of breast cancer: But we at deCODE and others have invested years of research and tens of millions of dollars to find other factors that can complement the conventional factors. Our efforts have paid off, because there are 7 genetic markers, easily and accurately measured from a cheek swab, that define most of the genetic risk for the common forms of breast cancer. The test defines risk from 0.4-fold to 4-fold compared to the general population risk (the average woman of European ancestry in the US has a lifetime risk of 12%). Based on this test alone, 10 percent of women have risks ranging from 1.4- to 4-fold, and would account for about 17 percent of breast cancer cases. Five percent of women are at more than 2-fold average risk, and the 1 percent are at 3-fold risk, so the risk is substantial for a significant portion of the population.

This risk is independent of family history and other conventional risk factors and therefore may identify some women as having higher risk even if breast cancer does not appear to be in their families. So Arthur Caplan is fundamentally incorrect in stating that only women with a family history of breast cancer would benefit from genetic testing. That may be true for traditional genetic diseases like Huntington’s disease and the rare highly familial form of early breast cancer addressed by the Myriad test, but the new tests for common diseases define risk beyond family history.

Each of the genetic markers in this risk test have been replicated in between 5 and 30 different populations in studies by deCODE genetics, the National Cancer Institute, and UK Cancer Research. These studies have been published in the most prestigious, peer-reviewed journals, including Nature Genetics and the New England Journal of Medicine. Altogether almost 100,000 patients and controls have been studied to define the marker risks. We made this test available for physicians to order for their patients through our reference laboratory which is regulated under CLIA by the US Federal government.

However, it is important to emphasize that the test does not diagnose breast cancer: it is simply a means of assessing personal risk of the disease, much more analogous to an LDL-cholesterol test for assessing heart disease risk than traditional genetic tests for purely genetic rare disorders like that for Huntington’s disease. That is, women at higher risk based on deCODE Breast Cancer are not destined to develop breast cancer. They may have a 20 to 36 percent lifetime risk for developing cancer (versus baseline risk of 12%). Women at lower risk are not immune from breast cancer and therefore would still be regularly screened with mammography. Women at higher risk above a certain threshold may benefit from more intensive screening using breast MRI on top of mammography, as recommended by the American Cancer Society. Also, certain medications such as tamoxifen which blocks the estrogen stimulation of breast cancer cells are approved by FDA to reduce breast cancer risk for women at higher risk.

In summary, this test may reclassify as higher risk some women who were previously considered to be of average risk, contributing to earlier detection and more focused prevention strategies. In fact, this test together with family history could define as higher risk the roughly 20% of women who may account for 35 to 40% of future breast cancers.

Looking at the big picture, about 5 percent of the health care budget is used for diagnostics and most of the rest is for therapeutics. Much money has been invested in the development and use of new expensive therapies for women with advanced cancer. But individual women and our healthcare system may both benefit from the increased use of risk diagnostics to help to focus on women at higher risk and thus diagnose cancers earlier rather than later, saving lives, suffering, and money.

Anyone who wants to hear some real stories from real people about how genetic tests like this may improve healthcare can find them on this blog.

Jeff Gulcher MD PhD
Chief Scientific Officer
deCODE Genetics

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.

Science journalist Boonsri Dickinson

Discover magazine reporter Boonsri Dickinson recently tried out deCODEme, as well as two other genetic scans offered by California-based websites. She discusses her results, and talks to several people who question whether genetic scans should be available to the public. Dickinson seems to be happy she had the chance to take a look at her genome, and went over her results with deCODE CEO Kari Stefansson. She notes that as “deCODE is known for discovering genetic risk factors…I decided to use deCODEme to validate the other two,” concluding that “deCODE genetics was authoritative.” Her article, ‘Inside Out: A DNA Diary,’ appeared on newsstands in August and can be found on the Discovermagazine.com website.

Link: Read abstract in Nature Genetics

In a recent interview Dr. Kari Stefansson, C.E.O. of deCODE genetics talked about the future for genetic tests such as deCODEme and how he believes that they will drive the shift from intervention to prevention in medicine

Lauralee Nygaard, a periodontist from Spokane, WA, says the deCODE tests are easy to take and highly cost effective but that we have to pay close attention to the results and be prepared to make some serious lifestyle changes.

Lauralee Nygaard is a dentist from Spokane, Washington. She is in her early forties and has two young children. Three years ago Lauralee had a stroke while she was performing surgery on a patient. It confirmed her suspicions about a predisposition to heart disease that she had nurtured since she was 18.

“When I was 18, I went to the doctor and said, ‘I know I’m at risk for a heart attack, my dad has hypercholesterolemia.’ The doctor laughed at me. He said, ‘you’re a skinny girl, you’re never going to have heart disease.”

A stroke at forty confirmed her worst fears: “It corroborated the fact that I knew I was at risk. I had pushed my family physician for years to be aggressively preventative with making sure I didn’t have heart disease. He always told me there was nothing they could do.”

As a dentist who had stressed the importance of preventative care for years, Lauralee was ready to practice what she had preached

Finding the right program

Lauralee had heard about the Heart Attack & Stroke Prevention Clinic in Spokane, Washington from some of her patients who had been through the program there and spoken very highly of it. She was impressed from the very start:

“For me it was one of the most unique health care experiences. My first appointment was three hours long—I had never spent three hours in a physician’s office! They spent a lot of time looking at my family history, asking questions about my uncles and my aunts and other people in the family, and going over my symptoms and educating me about heart disease and we did some follow-up tests.”

After taking the deCODE test she discovered, alarmingly, that her risk for heart attack and stroke was considerably higher than the average.

The program at Heart Attack & Stroke Prevention Clinic was quite unlike anything she had experienced before: “I had seen my physician annually for my entire life. I’d always had perfect blood pressure, always had perfect blood work. So, for them to say that ‘well, you had a stroke we’re not sure why’—I just thought, what did they miss? I mean there’s got to be something else. That was just really disturbing. Was I at risk because someone missed something?”

Lauralee expressed her disappointment and frustration with what she calls the ‘five-minute, drive-by doctor’s appointment’. She explains: “even if a physician wants to give you options, he’s not allowed to if he’s on certain insurance plans,” and that most physicians are restricted under the present system.

However, she insists that paying out of her own pocket at the Heart Attack & Stroke Prevention Clinic allowed nurse practitioner Amy Doneen “to have time with patients and be more preventative in terms of her approach to disease.” Lauralee adds that the costs of preventative treatment, as opposed to those incurred after an incident such as stroke or heart attack, are minimal.

The benefits of genetic testing
“To me, the benefit of doing the genetic test is that I can reduce my risk of having another stroke and permanent damage. It’s a short life, you know . . .”

deCODE offers genetic testing for a range of inheritable diseases. This, Lauralee believes, is part of a more efficient and more cost effective method of treatment.

“The motivation for me to follow through with the genetic test was the fact that my mother’s health had been failing rapidly and she had had four strokes in the last six months. She had just been diagnosed with diabetes and was not doing well. I had never really figured out why I had a stroke. Then Amy Doneen at Heart Attack Prevention Clinic suggested that atrial fibrillation (irregular heart rhythm) might have played a role. She explained to me that 30% of cryptogenic stroke diagnosis comes from atrial fibrillation and that this condition was ‘preventable’ with the right medication.”

To her surprise, Lauralee tested negative for the diabetes gene she believed she had inherited from her mother. But the test results affirmed that her stroke has not been a random catastrophe and she did indeed have a genetic disposition for atrial fibrillation. The next step was to take blood thinners that would reduce the risk of clotting after irregular heart rhythm and subsequently reduce the risk of having a stroke.

“The genetic test gave me information (that confirmed with my past stroke) that I am at risk for future strokes. Now, instead of saying, ‘Oh well, I had a stroke. I got lucky—no big deal,’ I can actually make some choices with my health care and avoid another stroke altogether.” Lauralee’s mother had suffered a series of strokes over a short period of time and she did not want to follow along the same path.

“My kids are little—I have kids that are 8 and 10 years old and I would like to be around to see them become productive adults. I think if I could gain some information, I’d be more proactive in my health—I think there’s a lot of benefit in that.”

By the same token, she believes that her children have “so many more preventative options” and could be tested at a much younger age and therefore hopefully avoid an incident altogether. She did not want them to have to wait till 40 or 50 and/or the occurrence of a massive event. Finding out early that they could be at risk would mean earlier intervention.

Modifying behavior for optimum health
Lauralee explains a healthy future is a matter of first getting as much information as possible and then modifying one’s behavior:

“I think things are changing. We’re learning more about how being aware impacts people. I think the more you can learn about your risks, the more you can modify your behavior and the more you can hopefully prevent something that’s going to harm or shorten your life.”

Of course, knowledge can be intimidating, but only if one is not willing to make lifestyle changes. Lauralee claims that the people who are frightened of what genetic testing can offer are mainly those who don’t want to change how they’re living. She admits she had to make some serious changes in her own life, changes that she frowned on several years before her stroke.

Cost effective
Lauralee says some people are naturally concerned about costs and the fact that their insurance might not pay for genetic testing. However, if you find out you are at risk before you damage anything, you can save a great deal. She believes that preventative medicine and genetic testing are highly cost effective!

“We know that a simple swab from the inside of your mouth can gauge your disease risk—that’s a very cost effective test to figure out what your disease predispositions are. Certainly, being more aggressive in prevention is going to lower health care costs over time. For example, it would have cost a lot less for me to know that I was at risk than to have 3 MRIs—in terms of health care expense. On the national scale, heart disease, diabetes, and stroke are some of the greatest issues facing health care in this country at the moment and they’re eating up a good chunk of our health care budget.

Better decisions, better health
After describing the test as “ridiculously easy,” Lauralee admitted that some fears were “a generational issue.” Younger people are much more comfortable with technology and knowledge and do not regard knowing what their genetic makeup is as threatening. People will soon learn that knowledge is power and that it allows us to take better care of our health and make better decisions. She admits, though, that any fears she might have had are allayed by a background in biology. She certainly did not shy away from being proactive: “I mean, I think that you can never ever regret what you invest in taking care of yourself. One body, one life, one chance.”

Does that mean she was glad to have an early warning?

“Yes, totally—it was a blessing. I was very fortunate I got a warning and could shape a path for myself. Not everyone does. 70% of all first heart attacks or strokes result in death for patients.”

She ends by telling us how the pharmacist reacted to her new medication regime:
“My pharmacist, who looks sixteen, said: ‘Can I ask you a personal question? Why are you taking all this medicine?’ (blood thinners, blood pressure and cholesterol medications) I said ‘you mean the medicine of an 80-year-old?—that’s because I want to live to be 80!’”

As the founder and CEO of deCODE, I want to welcome you to our blog, deCODEyou. This is a place where you can learn not just about deCODE’s discoveries and products but what others are saying about our work and about the application of human genetics to healthcare. We also hope that it will become a place where we can hear from you.

We are at a fascinating juncture in the application of genetics to the practice of healthcare. When we set out to try to search for the genetic causes of common diseases more than a decade ago, we took the approach that what we were doing was fundamentally a data mining challenge. We were trying to find correlations between two datasets: diseases or other phenotypes on the one hand, and variations in the sequence of the human genome on the other. This was a task for which computers were ideally suited. This fundamental insight has served us well, and as we assembled very large population-based datasets on disease, genotypes, and genealogy, advances in genotyping technology, computing power and our own data mining algorithms have enabled us to discovery major genetic risk factors for dozens of the biggest public health challenges of our time.

The purpose of understanding the genetics of disease was to use that information to create new means of diagnosing, treating and preventing disease.

As you know, one of the things we at deCODE are focused on now is turning our discoveries into tests for better assessing individual susceptibility to many common conditions, and, through our pioneering genome analysis service deCODEme™, enabling individuals to put themselves in the context of all that we are learning about human genetics.

And once again, the technology is helping us to bring understanding of genetics to people around the world. Unlike a large number of other companies hoping to follow on our heels, deCODEme is not just a website that happens to be about human genetics; it is your portal into the world’s largest and most successful effort to understand the inherited risk of the most common diseases in contemporary society. And the same technology that enables us to give deCODEme subscribers a secure, constantly updated profile of how you fit into what we are learning about the genome, also enables us to launch this blog and to engage you in a conversation about how we should use this information as individuals, healthcare systems and societies, to make our lives healthier and more productive.

As we make discoveries we are, by definition, opening up new possibilities and breaking new ground. We are very excited to be at the forefront of this work and hope that you will join us in this conversation.

Yours truly,

Kari Stefansson

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.