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One of the SNPs is located near the neurogranin gene (NRGN) on chromosome11. NRGN may be a candidate drug target, as it appears to play an importantrole in regulating both memory and cognition, processes that are oftenperturbed in schizophrenics. Another SNP is in the transcription factor 4(TCF4) gene on chromosome 18, which is involved in brain development. Five ofthe SNPs are located very closely together in the Major HistocompatibilityComplex, a region on chromosome 6 densely packed with genes regulating immuneresponse. This lends support to previous research suggesting a possibleenvironmental link between schizophrenia immune response. It has long beenknown, for example, that a disproportionately large number of schizophrenicsare 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 isassociated with a modest increase in risk.
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"Genetics offers a unique window for better understanding diseases likeschizophrenia because the brain and cognition are so little understood and sodifficult to study. Discoveries such as these are crucial for teasing out thebiology of the disease and making it possible for us to begin to developdrugs targeting the underlying causes and not just the symptoms of thedisease. One of the reasons this study was so successful is itsunprecendented size. Pooling our resources has yielded spectacular results,which is what the participants from three continents hoped for. At the sametime, this study underscores the fact that rare variants may well carry asignificant part of the genetic risk of schizophrenia, so our next task is touse 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 consortiumconducted a genome-wide scan of more than 300,000 SNPs in a total of 17,000patients and controls from England, Finland, Germany, Iceland, Italy andScotland. The 1500 SNPs with the best signal were then analyzed in 11,000patients and controls from the International Schizophrenia Consortium (ISC)and the European-American portion of the Molecular Genetics of Schizophreniastudies (MGS). Twenty-five SNPs with strong suggestive correlation were thenfollowed up in more than 20,000 patients and controls from the Netherlands,Denmark, Germany, Hungary, Norway, Russia, Finland and Spain. Bringingtogether the results of different consortia established he associationbetween the the total of seven markers on chromosomes 6, 11, and 18 withincreased risk of schizophrenia.
Acknowledgments
deCODE and all of the authors would like to thank the participants whotook part in this study and made it possible. The SGENE consortium and itsaffiliated groups include deCODE genetics, the National-University Hospitalin Reykjavik, the University of Aberdeen, the Ravenscraig Hospital inGreenock, the Institute of Psychiatry at King's College London, the NationalPublic Health Institute in Helsinki, the Ludwig Maximilians University andGlaxoSmithKline's Genetic Research Center in Munich, the University ofCopenhagen, the University of Oslo, the University of Heidelberg, theUniversity of Bonn, the University Medical Center of Utrecht, NijmegenMedical Center, the University of Verona, the Duke University Center forPopulation Genomics and Pharmacogenetics and the University of Sichuan,China. Follow up cohorts included those from Aarhus University, the NationalSerum Institute, and Bispebjerg and Glostrup hospitals, Denmark; SemmelweisUniversity, Budapest; the Mental Health Research Center of the RussianAcademy of Sciences; the Universities of Valencia and Santiago de Compostela,and the Hospital General Universitario Gregorio Maranon, Madrid, Spain; TheNorthern Finland Birth Cohort; Karolinska Institutet, Stockholm; Universitiesof Amsterdam, Utrecht and Maastricht, the Netherlands. The institutionscomprising the ISC and MGS can be found in papers published concurrently withthe present study in the online edition of Nature.
Funding for the work included in this study was provided by the EuropeanUnion through the SGENE consortium (www.SGENE.eu), by grantsLSHM-CT-2006-037761, PIAP-GA-2008-218251, and HEALTH-F2-2009-223423; The U.S.National Institutes of Health; and the National Genomic Network of Germany.
About deCODE
deCODE is a bio-pharmaceutical company developing drugs and DNA-basedtests to improve the treatment, diagnosis and prevention of common diseases.Its lead therapeutic programs, which leverage the company's expertise inchemistry and structural biology, include DG041, an antiplatelet compoundbeing developed for the prevention of arterial thrombosis; DG051 and DG031,compounds targeting the leukotriene pathway for the prevention of heartattack; and DG071 and a platform for other PDE4 modulators with therapeuticapplications in Alzheimer's disease and other conditions. deCODE is a globalleader in human genetics, and has identified key variations in the genome(SNPs) conferring increased risk of major public health challenges fromcardiovascular disease to cancer. Based upon these discoveries deCODE hasbrought to market a growing range of DNA-based tests for gauging risk andempowering prevention of common diseases. Through its CLIA-registeredlaboratory, deCODE offers deCODE T2(TM) for type 2 diabetes; deCODE AF(TM)for atrial fibrillation and stroke; deCODE MI(TM) for heart attack; deCODEProstateCancer(TM) for prostate cancer; deCODE Glaucoma(TM) for a major typeof glaucoma; and deCODE BreastCancer, for the common forms of breast cancer.deCODE is delivering on the promise of the new genetics.SM Visit us on theweb at http://www.decode.com; on our diagnostics site athttp://www.decodediagnostics.com; for our pioneering personal genome analysisservice and new focused disease scans, integrating the genetic variantsincluded in these tests and those linked to another twenty common diseases,as well as for our new deCODEme Cardio(TM) and deCODEme Cancer(TM) scans, athttp://www.decodeme.com; and on our blog at http://www.decodeyou.com.
Any statements contained in this presentation that relate to futureplans, events or performance are forward-looking statements within themeaning of the Private Securities Litigation Reform Act of 1995. Theseforward-looking statements are subject to a number of risks and uncertaintiesthat could cause actual results, and the timing of events, to differmaterially from those described in the forward-looking statements. Theserisks and uncertainties include, among others, those relating to our abilityto obtain sufficient financing to continue as a going concern, our ability todevelop and market diagnostic products, the level of third partyreimbursement for our products, risks related to preclinical and clinicaldevelopment of pharmaceutical products, including the identification ofcompounds and the completion of clinical trials, our ability to formcollaborative relationships, the effect of government regulation and theregulatory approval processes, market acceptance, our ability to obtain andprotect intellectual property rights for our products, dependence oncollaborative relationships, the effect of competitive products, industrytrends and other risks identified in deCODE's filings with the Securities andExchange Commission, including, without limitation, the risk factorsidentified in our most recent Annual Report on Form 10-K and any updates tothose risk factors filed from time to time in our Quarterly Reports on Form10-Q or Current Reports on Form 8-K. deCODE undertakes no obligation toupdate or alter these forward-looking statements as a result of newinformation, future events or otherwise.Contacts: deCODE genetics Edward Farmer +44-7796-010107 [email protected] Gisli Arnason +354-570-1900 [email protected] Joy Bessenger +1-212-481-3891 [email protected]
SOURCE DeCODE Genetics Inc
