Pancreatic cancer has been added to the deCODEme Complete Scan. Pancreatic cancer is a particularly difficult form of cancer. It is virtually asymptomatic in its earliest stages. The cancer typically spreads rapidly and aggressively into surrounding tissue and organs, it is resistant to standard chemotherapy and has a strong tendency to recur. These characteristics make pancreatic cancer one of the most challenging cancers to treat unless caught early enough, and provide a grim prognosis for many diagnosed with the disease.

Currently there is no screening test available for this cancer, but genetic variants have been identified that are associated with increased risk of developing non-endocrine pancreatic cancer, the most common type of pancreatic cancer.  The deCODEme Complete Scan recently added non-endocrine pancreatic cancer to its genetic risk assessment profile.

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.”

We have just made some updates to the deCODEme ancestry service. Now you have more power and flexibility when you compare your genome with that of friends or individuals from different populations around the world.

Your genome can be viewed as a mosaic or tapestry made up of fragments of chromosomes from your ancestors. Fragments of chromosomes inherited from very recent ancestors, say grandparents, are expected to be large – typically tens of millions of nucleotides in size. As ancestors become more ancient, then the size of the chromosome fragments inherited from them become smaller – down to a few thousand or hundred nucleotides for ancestors born thousands of years ago.

Our new and improved genome comparison tool enables to you compare your genome with another individual in order to determine which chromosome fragments you share and to see how much of your genome is shared. The fascinating thing about this analysis is that each shared fragment represents a common ancestor. The number of shared fragments and their size reflects the number of common ancestors and how far back in time they are found. In other words, you can see how closely you are related.

When genomes are compared, your chromosomes are broken down into fragments of a particular size and sharing is evaluated for each fragment. Before the fragment size was fixed at 1 million nucleotides. Now you can change the size of fragments that are compared, from a minimum of 250 thousand nucleotides (250Kb) to a maximum of 20 million nucleotides (20Mb). The minimum fragment size will reveal shared chromosome fragments from common ancestors going back thousands of years. The maximum fragment size will reveal only shared chromosome fragments from very recent common ancestors – i.e. going back only a few generations. Setting the fragment size thus lets you select how far back in time you want to hunt for common ancestors.

This image shows results of a comparison between an Icelander and an Orkney Islander using a fragment size of 3Mb. The brown lines are shared fragments, inherited from common ancestors from more than 1000 years ago!

Scientists at deCODE genetics today report the discovery of seven novel and common single-letter variations in the sequence of the human genome (SNPs) that are involved in modulating the electrical impulses that govern the working of the heart. Two of these SNPs, which correlate with electrocardiogram (ECG or EKG) measurements that are used in the clinical evaluation of heart health and activity, were then shown to confer increased risk of atrial fibrillation (AF), one of the most common causes of irregular heartbeat and a leading cause of stroke. The paper, “Several common variants modulate heart rate, PR interval and QRS duration,” is published online in Nature Genetics and will appear in an upcoming print addition of the journal.

The deCODE team began by correlating ECG measurements with genome-wide SNP data from more than 40,000 Icelandic participants in its gene discovery program. This search identified one novel SNP influencing heart rate and four each linked to PR interval and QRS duration, measurements of how quickly the electrical impulses that cause the heart muscles to pump achieve their purpose. Intriguingly, SNPs on chromosome 3 linked to both longer PR interval and QRS duration are in the gene encoding SCN10A, a sodium channel that has never before been linked to heart activity. Individuals with the same variants were also more likely to have been fittted with a pacemaker. A follow-on analysis of all of the novel SNPs in Icelandic and Norwegian heart patients and controls demonstrated the association of two of the SNPs linked to PR interval to risk of AF, and another SNP to increased risk of advanced atrioventricular block. Two other papers published today in the same journal provide further validation of some of the deCODE findings.

“Over the past two years, we have discovered major genetic risk factors for heart disease and stroke and introduced tests for these risk factors into clinical practice. We are building the power of these tests through our ongoing discovery work, and today’s findings demonstrate again the fruitfulness of using intermediate risk factors and clinical measurements as entry points for finding risk factors for disease. Our population resources enable us to do so efficiently and with exciting results. These latest findings will be incorporated into our deCODE AF test and deCODEme scans,  and certain of these discoveries may also provide opportunities for out-licensing for therapeutic development,” said Kari Stefansson, CEO of deCODE.

Season’s Greetings And Best Wishes For The New Year from deCODE.

We at deCODEme just wanted to let you know that we have added a Forum where you can discuss genetics, ancestry and health. Our experts are looking forward to your questions and comments so we hope you take advantage of this new feature.

We are constantly working on making deCODEme more valuable and informative and we appreciate your continued interest.

We hope you have a pleasant and festive holiday.

The deCODEme Team

Hypertension genetic risk now a part of the deCODEme Complete Scan

Hypertension, commonly referred to as high blood pressure, has been added to the deCODEme Complete Scan. Hypertension is defined as blood pressure of 140/90 mmHg or above on three consecutive measurements at least six hours apart. Blood pressure this high is a risk factor for many diseases. Over time, the increased workload on the heart weakens it and contributes to atherosclerosis (the thickening of the arteries due to fat and cholesterol depositions), thereby increasing the risk of coronary heart disease and stroke, which are among the leading causes of death in the United States. High blood pressure can also lead to other conditions, such as heart failure, kidney disease, and blindness. High blood pressure is especially dangerous because it often has no obvious warning signs or symptoms and can therefore remain undiagnosed and untreated long enough to cause damage. High blood pressure is common, but too often goes undetected. An estimated 1 billion people worldwide have hypertension, and this number is expected to increase to 1.56 billion people by the year 2025. This translates to about 1 in 4 adults being afflicted with hypertension worldwide. Currently, about 1 in 3 Americans are thought to have hypertension, and a third of them probably do not know it.

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.

Systemic Lupus Erythematosus is a complex disease and often difficult to diagnose – knowing your genetic risk may help your doctor rule out or confirm Lupus.

Systemic Lupus Erythematosus has been added to the deCODEme Complete Scan. Lupus is an autoimmune disease characterized by intermittent flares of inflammation in various tissues of the body. Autoimmune diseases occur when the body’s tissues are attacked by its own immune system. Normally, people produce antibodies that attach themselves to infectious agents when they enter the body and mark them for destruction by the immune system. People who have Lupus produce abnormal antibodies that target tissues within their own body. Lupus can therefore cause inflammation and tissue damage in various organs such as the skin, heart, lungs, kidneys, joints, and even the nervous system. If you already have a deCODEme Complete Scan you can now log in to see your genetic risk for Systemic Lupus Erythematosus. If you want to purchase a genetic test visit the deCODEme store.

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.

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

Dr. Kari Stefansson receives Jahre Award - Photo by Francesco Saggio, University of Oslo

In a ceremony held this evening in Oslo, deCODE founder and CEO Kari Stefansson received the Anders Jahre Award for Medical Research. One of the most prestigious medical prizes in the Nordic countries, it was awarded in recognition of Dr. Stefansson’s leading contribution to increasing understanding of the genetic factors involved in common, complex diseases. The selection committee noted that this work has been driven by deCODE’s population approach, and by the participation of a large proportion of the Icelandic population in the company’s gene discovery programs.

Photo by Francesco Saggio, University of Oslo

Photo by Francesco Saggio, University of Oslo

Knowing your risk for Chronic Kidney Disease through a deCODEme DNA scan can increase your awareness and empower you to take preventive steps to protect your kidneys.

Chronic Kidney Disease has been added to the deCODEme Complete Scan. Chronic Kidney Disease involves the gradual loss of kidney function over time that can ultimately lead to kidney failure. It typically develops as a result of other common diseases, primarily diabetes, high blood pressure and obesity, but not everyone has the same risk of developing Chronic Kidney Disease. Research suggests that this disease has a strong familial component.

In the U.S., an estimated 26 million adults have Chronic Kidney Disease, but most of them do not know it. The kidneys have such a remarkable ability to compensate for problems in their function, that there may be no symptoms of Chronic Kidney Disease until it has progressed considerably.

Recently, scientists identified a common genetic variant (rs4293393-T), associated with increased risk of Chronic Kidney Disease. deCODEme has incorporated these results into the complete genetic scan, which analyzes your DNA and provides you with a personalized risk assessment for Chronic Kidney Disease and about many other diseases, including diabetes, obesity and kidney stones.

Chronic Kidney Disease is a growing problem in the U.S. and in other western parts of the world, Knowing your risk for Chronic Kidney Disease can increase your awareness and empower you to take preventive steps to protect your kidneys.

deCODEme Complete Scan now includes Testicular Cancer

At deCODEme, we believe that when it comes to planning your preventive health efforts, your genetic profile is the place to start. This month we have added two new diseases, both of which are highly curable if caught early.

If you are a deCODEme customer who has bought our Complete Scan, your account now includes a personalized genetic risk assessment for:

Testicular Cancer of males, and Ovarian Cancer of females.

Our scientists have also added more genetic details to the risk assessment for Prostate Cancer, which now includes a total of 25 genetic risk variants for customers of the Complete Scan.

deCODEme DNA test now includes Ovarian Cancer

Ovarian cancer is the eighth most common cancer in women. Based on ovarian cancer statistics in the U.S., it is expected that 1.4% of women born today will be diagnosed with cancer of the ovary at some point during their lifetime. This represents the lifetime risk of ovarian cancer and means that 1 out of every 71 women will be diagnosed with this disease during their lifetime. deCODEme Complete Scan now includes risk calculation for Ovarian Cancer.

Genetics is a major risk factor for ovarian cancer

Although many environmental and lifestyle factors affect the risk of ovarian cancer, the single greatest known risk factor is a family history of the disease. This indicates that genetics is a major risk factor. Scientists already know that variants in the BRCA1 and BRCA2 genes significantly increase a woman’s chances of developing ovarian cancer. However, these variants are rare and account for less than 5% of all ovarian cancers. Recently, scientists have discovered a common variant on chromosome 9 that can increase a woman’s risk of developing the most common type of ovarian cancer (epithelial cancer). This variant is found in approximately 70% of women of European descent.

deCODEme provides personalized access to some of the first genetic variants recently linked to the most common type of brain cancer - Glioma

There are various types of brain cancer. Brain cancer can be primary, when it starts from cells in the brain, or secondary, when the cancer starts in another part of the body (for example in the lung or breast) and spreads to the brain through the bloodstream (that is through metastasis). Brain tumors can also be either benign (non-cancerous) or malignant (with cancer cells that multiply uncontrollably).

A glioma is a malignant primary brain cancer that originates from so-called glial cells found within the brain. There are several different types of gliomas determined by the type of glial cell that gives rise to the tumor. Although gliomas are rare, they are the most common type of primary malignant brain tumor in adults. They account for up to 80% of all brain cancer cases, with around 21,000 individuals diagnosed every year in the USA.

You may have heard about glioma in the news recently as this was the type of malignant brain cancer that recently claimed Senator Edward M. Kennedy’s life at age 77. The causes of gliomas are largely unknown. However, scientists have long suspected that genes play a role, making some individuals more likely than others to develop brain cancer. Now some of these genes have been found. A study published in Nature Genetics in July, 2009, reports on the identification of the first common genetic variants known to contribute to an increased risk of developing this type of brain cancer. The deCODEme team has reviewed these findings and added them to the deCODEme Genetic Scan . On the basis of this newly published knowledge, we can now provide customers of European descent with a personalized interpretation of their genetic risk for developing a glioma-type brain cancer.

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.

It’s Not Just the Sun: deCODE Discovers Sequence Variants Affecting Susceptibility to Skin Cancer.

Scientists at deCODE genetics and academic colleagues from Europe and the United States today present in the journal Nature Genetics the discovery of common genetic risk factors for basal cell carcinoma (BCC) that affect people with fair and dark complexions alike. deCODE had previously discovered five common single-letter variants in the sequence of the human genome (SNPs) linked to risk of BCC, the most common cancer in people of European descent. However, most of these earlier findings were also correlated with fair skin, well known to accompany vulnerability to the damaging effects of ultraviolet radiation in sunlight. By contrast, three of the SNPs presented today do not correlate with light pigmentation…

and may thus provide new insight into the underlying biological perturbations that lead to BCC independent of environmental exposure. One of these, in the keratin 5 (KRT5) gene on chromosome 12, leads to a subtle but potentially damaging alteration to the KRT5 protein, which supports the structural integrity of the skin. Those with one copy of the variant are at more than 30% greater likelihood of developing BCC than those who do not carry the variant, while those who carry two copies are at more than 50% greater risk. Another of the SNPs is located on chromosome 9p21, the same region of the genome that deCODE has linked to increased risk of heart attack and others have linked to type 2 diabetes. deCODE used its population genetics resources in Iceland to demonstrate that a third risk variant, on chromosome 7q32, confers greater risk if inherited from the father than from the mother.

“It is important to find genetic causes of BCC that do not appear to be modulated directly by sensitivity to the sun. This may bring us closer to understanding the underlying biology of a very common form of cancer, and KRT5 in particular may point us to new pathways for developing new drugs or skin care products. We are also pleased to be able to fold these discoveries directly into our deCODEme™ scans. For sun exposure is still the most important risk factor for BCC, and while people with fair skin are already aware of the need to protect themselves when they go outdoors, others with darker complexions may also be at higher risk of BCC than they think. This is also one of the first reports of a sequence variant conferring risk of a disease that is dependent on the parent of origin. With all of our findings over the past year, we believe we have found variants that play a role in most cases of BCC,” said Kari Stefansson, CEO of deCODE.

The study also provided conclusive evidence that a previously identified SNP in the TERT-CLPTM1L region of chromosome 5 confers susceptibility to BCC but protects agains cutaneous melanoma. A previously known SNP in the SLC45A2 gene on chromosome 5 was confirmed to confer risk of squamous cell carcinoma as well as BCC. The study involved three stages. First, the SNPs with the best results from previous genome-wide scans of more than 300,000 SNPs were tested in large numbers of individuals with and without BCC. The first two phases included participants from Iceland, The Netherlands, Sweden, Germany, Italy, Hungary, Romania, and Slovakia. The SNPs on chromosomes 12, 9p21 and 7q32, as well as those on chromosome 5, were then tested and confirmed in participants from the United States and Spain.
In all, the study included genotypic data from some 45,000 people. deCODE and its collaborators would like to thank those who took part for making the work possible. Financial support for various portions of the work was provided by the US National Institutes of Health (grants T32E007155, R01CA082354, and R01CA57494), Radboud University Nijmegen Medical Center, the Netherlands, the National Bank of Austria, the Radiumhemmet Research Funds and the Swedish Cancer Society.

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.