Building global networks for human diseases: genes and populations

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COM M E N TA RYThis years Days of Molecular Medicinemeeting, organized by the Institute ofMolecular Medicine of the University ofCalifornia, San Diego, in collaboration withNature Medicine and the Wellcome Trust, wasthe first meeting in this series to be held out-side the United States. The venue was theSanger Centre (Hinxton, UK) and the topic ofthe meeting was Integrative Physiology andHuman Disease: Neurohormonal andMetabolic Pathways. Embedded in the vari-ous scientific sessions was a forum onBuilding Global Networks for HumanDiseases: Genes and Populations. The aim ofthis forum was to look at different examplesof national networks for the genetic study ofhuman disease and at the potential for futurecollaborations between scientists in NorthAmerica and Europe with science communi-ties elsewhere, particularly in developing andrestructuring countries.One of the most important challenges offuture biomedical research will be to dissectthe interplay between genetic makeup andenvironmental influences on the pattern ofdiseases worldwide1,2. With the humangenome available, it will be essential to iden-tify disease genes as a prerequisite to design-ing adequate diagnostic tools, drugs andvaccines for therapeutic interventions. In thisprocess, biobanksdepositories of vast num-bers of DNA samples, together with data onthe health history of the donorshave a cru-cial role. But to be successful and provide use-ful information on the genetic factorsassociated with disease and their interactionwith environmental factors, an ideal biobankmust fulfill several requirements. It should berepresentative of the population and ideallyshould contain samples and data from at least500,000 subjects. There should be a goodintegration of clinical data over a long timeperiod and, preferably, linked multigenera-tional information. And the results thatemerge from its analysis must be susceptibleto validation, a process that requires access todata from other populations of differentgenetic background.Many countries either have already set upbiobanks or are about to do so. The UKBiobank (see Table 1 for a listing of biobanksand websites), a project jointly funded by theMedical Research Council (MRC), theWellcome Trust and the Department ofHealth, will include data on 500,000 peoplewhen fully established. In Canada, theCARTaGENE project will include informa-tion on 60,000 people. A European project,GenomEUtwin, will incorporate data on600,000 pairs of twins by coordinating exist-ing national twin registries, of which thelargest is the Swedish Twin Registry at theKarolinska Institutet, with data from 80,000pairs of twins.But in spite of their seemingly overwhelm-ing size, greater networking between thesenational initiatives could only further benefitour understanding of the most commoncauses of morbidity and mortality. Countriesof the developing and restructuring worldhave a great deal to offer in this context, as washighlighted by many examples presented atthe forum.George Chandy, director of the ChristianMedical College (Vellore, India), and QuasimMehdi, director general of the Biomedical andGenetic Engineering Laboratory (Islamabad,Pakistan), gave an overview of the researchportfolios of their institutions. In both coun-tries there are unique opportunities for col-laboration with research communitiesworldwide. Both nations have uniqueresources at their disposal. India and Pakistanare homes to a wide variety of ethnic groupswith specific patterns of disease. In addition,consanguineous marriages are very commonin both countries. This cultural feature has ledto a clustering of congenital diseases, whichcan be followed by establishing family trees.Good medical records going back many yearsare available, and in India they are often inEnglish. These assets could prove to be a goldmine when brought together with the latesttechnological platforms that are available tocountries with greater financial resources. Inboth India and Pakistan, research programsinvolving population-based studies arealready underway. Despite all these efforts,however, there is still a needwhich wasclearly expressed at the meetingto attractexternal funding and establish internationalcollaborations with scientists from developedcountries.There are other areas of research where col-laborations between the scientific communi-ties of the developing and the more developedworld would be mutually beneficial. Diseasepatterns in the western world have shiftedmarkedly over the past decades from infec-tious to noncommunicable diseases, and thisBuilding global networks for humandiseases: genes and populationsHans-E Hagen & Jan Carlstedt-DukeBiobanks will have a crucial role in the identification of genes associated with disease a prerequisite to designingadequate diagnostic and therapeutic tools. To maximize their impact and chances of success, collaboration at aglobal scale is highly desirable.Hans-E Hagen is at the International BiomedicalProgramme, The Wellcome Trust, London, UK, andJan Carlstedt-Duke is at the Karolinska Institutet,Stockholm, Sweden.e-mail: MEDICINE VOLUME 10 | NUMBER 7 | JULY 2004 6652004 Nature Publishing Group M E N TA RYphenomenon is increasingly observed inother parts of the world, including India andPakistan. This could offer a prime opportu-nity to investigate the mechanisms underly-ing the association of changes in life style withshifts in health patterns, such as the growingproblems with obesity, diabetes and atopicdiseases (for example, asthma), especially inchildren. Both India and Pakistan have goodscientific infrastructure, with excellentnational research centers that could becomeinvolved in research of this sort.Another biobank presented at the forumwas the Estonian Genome Project, a brain-child of Andres Metspalu of the University ofTartu. A pilot project, which has been wellreceived by the Estonian public, is collectingthousands of blood samples as well as themedical histories of the donors, aiming even-tually to collect the DNA samples and med-ical records from a million Estonians. Theproject is a massive undertaking, consideringthat the overall population of this new mem-ber of the European Union is only 1.4 mil-lion. The goals are (i) the identification ofdisease genes through comparison of geno-types within groups of patients with a givendisease and (ii) the creation of a health caredatabase (health history and genealogy)offering free access for Estonians to their ownrecords. The hope is that Estonians will beable to use their country profile to theiradvantage. Estonia has decided that, as asmall country, it will have to concentratestrategically on a few areas of scientificresearch that relate to its existing strengths;molecular biology and population geneticsare two of the selected areas. Estonia is asmall nation, with a good primary health caresystem, where such an ambitious project isprobably easier to manage that in a largercountry. Its scientific and technologicalinfrastructure are well developed, and laborand overhead costs should be considerablylower than in most western countries. Inaddition, tremendous efforts have been madeto restructure the scientific landscape duringthe period running up to full EU member-ship, which was formally achieved on 1 May2004. However, the Estonian research com-munity still needs more funding from exter-nal sources to develop its science basefurther. If the goals of the Estonian GenomeProject could be achieved successfully, itwould make Estonia an even more attractivepartner for other research communitiesworldwide in their hunt for genes associatedwith disease.A final example, albeit one at a ratheradvanced stage of completion, comes fromIceland. After purchasing the IcelandicGenealogic Database from its government,the Icelandic biotech company deCODEGenetics is now using this database, in con-junction with genotypes of some 100,000samples from volunteers, to identify thegenetic bases of common diseases. At theforum, deCODE chief executive KariSteffansson gave an overview of the areas inwhich the company has been particularly suc-cessful. Their genealogy database includesmore than 95% of all those who have lived inIceland since the first census in 1703 andstretches back to the ninth century. In all, thedatabase contains 680,000 entries. The strat-egy developed by deCODE is based on theintegration of genetic, clinical and genealogi-cal data. This enables the identification ofvery small genetic regions shared by relatedpatients and the isolation of key disease genesfrom these regions. Using this strategy,deCODE researchers have isolated 15 specificdisease genes and located genes involved inmore than 25 of the most common diseases.For instance, they identified the STRK1 locuson chromosome 5q12 (ref. 3) and showedthat genetic variation in the phosphodi-esterase gene PDE4D in this region is associ-ated with stroke4. This result wassubsequently replicated in a Scottish strokecohort. A second gene, ALOX5AP, which isinvolved in leukotriene metabolism, was alsoassociated with stroke5. The same gene hasbeen shown to be associated with myocardialinfarction in a British population. Both ofthese disease-specific genes are candidate tar-gets for the development of new pharmaceu-tical agents.Scandinavian populations have proven tobe very informative in clinical genetic andepidemiological studies, for several reasons.The countries have relatively small popula-tions, with regions that are relatively isolated,and well-documented family, social andhealth records going back many generations.The national health care systems are publiclyfunded and encompass the whole population.They are completely integrated within thesocial structure of the country and are basedon a unique personal identification number.In addition to the Icelandic example involvingdeCODE, other institutions that have madeuse of this system for long-term studies ofmajor interest include the Ume UniversityMedical Biobank, which contains data from85,000 people, and the national twin registriesof Sweden, Denmark, Norway and Finland,with data from 80,000, 65,000, 55,000 and45,000 pairs of twins, respectively. These largecollections of clinical data and registries inte-grated with clinical data make it possible tocarry out large case-control studies despitethe relatively small populations of thesecountries.However, one of the larger collections ofclinical material available today was createdby a commercial enterpriseGenomicsCollaborative, Inc., based in Cambridge,Massachusetts. Their collection encompassesdata from 120,000 patients and is used in col-laborative projects with key industry and aca-demic partners. Other large collections arenoncommercial and integrate multinationalcollections. Examples include the EuropeanProspective Investigation into Cancer andNutrition (EPIC) at the International Agencyfor Research on Cancer (IARC; Lyon), whichhas material from 520,000 individuals, andthe Medical Research Council (MRC)/CancerResearch UK/British Heart Foundation(BHF) Clinical Trial Service Unit at the666 VOLUME 10 | NUMBER 7 | JULY 2004 NATURE MEDICINETable 1 Selected biobanksInstitution WebsiteUK Biobank Twin Registry Genome Foundation Genetics University Medical Biobank Twin Registry Collaborative, Inc., Prospective Investigation Cancer and Nutrition (EPIC)MRC/Cancer Research UK/BHF Trial Service Unit & Epidemiological Studies Unit2004 Nature Publishing Group M E N TA RYUniversity of Oxford, with material from250,000 individuals.The establishment and maintenance ofthese collections and databases, both for case-control and population-based prospectivestudies, require considerable investment butcan potentially provide important opportuni-ties for diagnosing, treating and preventingmajor diseases. Public investment in theseprojects could potentially help reduce theever-expanding cost of health care in the longterm. Commercial interest, such as deCODEand Genomics Collaborative, can comple-ment the need for these large-scale publicinvestments. However, there are substantialrisks for conflicts of interest in this area, asillustrated by the conflict betweenUmanGenomics and the Ume UniversityMedical Biobank and by a developing contro-versy in Estonia concerning intellectual prop-erty rights6. These issues need to be addressedsoon to ensure the security of these resourcesin a manner that is of optimal benefit to pop-ulations on a broad scale.The aim of the forum was to highlight afew of the countries that could offer uniqueopportunities to the research communitiesworldwide. There will also be possibilitiesfor such collaborations in other parts of theworld, such China and Latin America. Theconcluding message was that, by bringingtogether those scientific communities ininternational collaborations and networksin an equitable fashion, a very powerfulalliance could be created to tackle diseases,which would be relevant both to the westernworld and to restructuring and developingcountries. It is essential that any suchalliance should include capacity buildingand maintenance in the partner countries ofthe developing and restructuring world, sothat both sides can profit mutually fromworking together on the health problems oftoday and tomorrow. In this realm, as inothers, science needs to transcend national,cultural, ideological and religious barriers,especially if there are potential global bene-fits from the outcomes of collaborativeresearch.1. Jimenez-Sanchez, G., Childs, B. & Valle, D. Humandisease genes. Nature 409, 853855 (2001).2. Peltonen, L. & McKusick, V.A. Dissecting humandisease in the postgenomic era. Science 291,12241229 (2001).3. Gretarsdottir, S. et al. Localization of a suscepti-bility gene for common forms of stroke to 5q12.Am. J. Hum. Genet. 70, 593603 (2002).4. Gretarsdottir, S. et al. The gene encoding phos-phodiesterase 4D confers risk of ischemic stroke.Nat. Genet. 35, 131138 (2003).5. Helgadottir, A. The gene encoding 5-lipoxygenaseactivating protein confers risk of myocardialinfarction and stroke. Nat. Genet. 36, 233239(2004).6. Rose, H. An ethical dilemma: the rise and fall ofUmanGenomicsthe model biotech company?Nature 425, 123124 (2003).NATURE MEDICINE VOLUME 10 | NUMBER 7 | JULY 2004 6672004 Nature Publishing Group


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