Opportunities for Future Biobanking in Europe

Leaders: Paolo Gasparini, Andres Metspalu

The use of isolated populations to reduce disease heterogeneity of complex disorders has already proven very useful in identifying DNA polymorphisms associated with complex diseases and quantitative traits (Peeltonen et al. 2000, Angius et al. 2002, Gianfrancesco et al 2003, Revsnidottir et 2003, Thorgeirsson et al 2003, Krjstiansson et al 2002, Peeltonen et al.2004). The study of complex traits in geographically and culturally isolated populations is particularly useful because the entire population can be analysed, the relative weight of environmental variation can be controlled and genetic factors can be more easily identified. In these genetically and culturally homogeneous populations, a large proportion of individuals presenting a given trait is likely to share the same trait-predisposing gene inherited from a common ancestor. Furthermore, inbreeding, typical of small communities, reduces genetic heterogeneity and increases homozygosity, providing greater power for detection of susceptibility genes.

Aims and objectives

a) to identify new opportunities for biobanking in Europe with a particular focus on genetic isolated populations.

A survey to identify completed, ongoing or planned European biobanking initiatives with a particular focus on studies of isolated populations will be carried out during the first 12 months of the CA. Currently, there are several initiatives in Italy, as well as in Croatia, Sweden, Iceland, Finland, The Netherlands and Scotland. Additional ones are planned in Romania, Greece, Israel, and Spain. This survey will be performed during the first year of the CA making use of literature review, web-searches, e-mail and telephone contact with known investigators as well as direct contact with representatives of each European country in Brussels. Final results, including a map showing the locations of key initiatives, will be made available as a report through the website for the CA. This activity will be carried out collaboratively with WP1 and WP3.

b) to establish common criteria for selection and collection of these populations.

We will aim to provide the international community with guidelines for the selection of genetically isolated populations for study. This work will sit nicely alongside the work programme of WP1 which is focusing on outbred populations. In addition, in collaboration with WP1 we will consider issues pertaining to harmonization of the assessment of phenotype and life-style exposure. Based on the collective experience within the CA consortium and of the larger expert group invited to contribute to the workpackage, we will explore standard criteria for selection of ideal populations for study which will include: availability of genealogical data; key parameters of population structure (e.g. number of founders, number of living inhabitants, endogamy rate, emigration/immigration rate); and the possibility of assessing and quantifying enviromental determinants. An expert group will be convened informally at the start of the CA with initial interaction taking place electronically or at face-to-face meetings that occur for other purposes. The group will meet formally at the Initial Conference for Population Biobanks for Health and will agree upon a refined strategy to take things forward (including interaction with other workpackages) and will identify any additional experts who should be coopted onto the group. They will subsequently meet electronically or informally, with the intention of producing a final report at 33 months which will then be presented and discussed at the Concluding Conference for Population Biobanks for Health. It will then be revised, as required, and posted on the CA web site.

c) to stimulate development of analytic tools. Many of the biostatistical tools that are used to describe genetic data, construct pedigrees or draw even simple statistical inferences are poorly configured for the study of genetically isolated populations. These populations have an abnormally strong latent structure, many idiosyncratic features, and a complexity which demands the development of specific tools. Thus, working closely with WP1, we aim to establish a network of statisticians, bioinformatics and software constructors with experience and expertise in working with genetic isolates to explore issues pertaining to database construction, statistical analysis (including statistical power), the construction and drawing of pedigrees and data mining. We will build upon strong pre-existing interactions with industry (including IBM and HP) and invite them to join the collaboration. Their involvement should help catalyse later attempts to produce final products such as new software and/or new algorithms.

d) to elucidate common ethical issues. Due to their unusual structure and setting, there are many social, ethical and legal issues that are particularly relevant to genetically isolated populations. In collaboration with WP5, we will explore the relevant issues. We will ensure that our expert group includes an ethicist with a special knowledge of genetic isolates and that there is cross-representation with the expert group on WP5. We will take into account the information about etical, legal, social and communication aspects in minorities that could araise from the Public Health project POSEIDON studies that address similar ethical issues in the context of campaign in minorities or specific populations for hematopoïetic stem cell donations.

Deliverables

D 1 Preliminary planning, strategy setting and identification of full expert groups for all

workpackages at Initial PHOEBE Conference.

Time: 6 months

D 2 Debriefing, presentation and discussion of final reports, and discussion of future strategy

for all workpackages at the Concluding PHOEBE Conference.

Time: 35 months

D 3 Final report to be posted on worldwide web.

Time: 36 months

D 16 Report on European population-based biobanks in genetic isolates
Time: 18 months

D 17 Final report to address issues specific to the study of genetic isolates pertaining to:

the selection of populations for study; statistical analysis, analytic tools and database

construction; and ethical-legal issues.

Time: 33 months

Milestones

The sole ”decision point” will occur at the Initial PHOEBE Conference when we identify the members of the expert group. Time: 6 months

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