The NIHR Cambridge BioResource A means of correlating disease susceptibility genotypes with phenotypes Bringing together local people and leading research

What is CBR? Volunteer Resource- Panel of 10,000 individuals aged 16 yrs and over living in and around Cambridgeshire who have donated DNA samples for genotyping. Established on a not-for-profit basis to assist local researchers with volunteer recruitment to a wide range of medical studies. It provides a sampling frame from which people can be selected on the basis of their genotype to be invited for observational studies or clinical trials looking to correlate genotype with phenotype.

CBR- 2 Staged Process Stage 1 –Establishing the panel-sourcing the participants –Sample and data collection –Organised as a collaborative activity (NIHR BRC, University, NHSBT, MRC) Stage 2 –Using the BioResource-recall of participants –Organised by individual groups in conjunction with CBR Management and Operations teams –Individual ethics applications MUST be submitted for each study

To aid rapid identification of large numbers of subjects meeting inclusion and exclusion criteria who can be approached for recruitment into a wide range of experimental medicine studies. To provide efficient access to homogenous subgroups of volunteers recalled by genotype and/or phenotype for proof of principle studies. To allow studies and trials to be targeted at subpopulations that are characterised by genotype and/or phenotype-improving our understanding of disease mechanisms, helping the identification of potential drug targets Why do we need CBR?

Applying to the CBR:

Responsibilities CBR Management Committee responsible for: –Establishment of BioResource and recruitment of participants into BioResource –Management of BioResource CBR SAB responsible for: -Access to the BioResource -Review of stage 2 study design- (allele frequencies and risk ratios (lower, neutral and higher risk genotypes studied and risk ratios less than 1.5, hence no labelling of selected subjects)) and required volunteer commitment in the study Individual researchers responsible for: –Ethical approval application for their own stage 2 study –All costs associated with individual study

Stage 2 studies Current Studies include: Cardiosome Project: Genes and mechanisms in cardiovascular disease (Dr Willem Ouwehand) Common copy number variants associated with obesity (Dr Sadaf Farooqi) Developmental origins of risk of type 2 diabetes: Tolerance of fasting and IGF-I levels (Prof David Dunger) GANDALF study: Genetic variation and altered leucocyte function in health and disease (Prof Ken Smith) Genes and mechanisms in type 1 diabetes (Prof John Todd) Genetic and cellular mechanisms protecting from tuberculosis (Dr Sergey Nejentsev) Investigation of the functional role of the IL23R gene variant in psoriasis pathogenesis (Prof Frank Nestle) Other Studies starting soon: An investigation of the functional consequences of the R77H polymorphism of human CD11b: a strong genetic susceptibility variant in systemic lupus erythematosus (Prof Tim Vyse) Approaches to early detection and intervention in lung disease (Prof Sir Bruce Ponder)

Recruitment of patients from clinics (thyroid, diabetes, Multiple Sclerosis, pain, asthma, pneumonia, lung cancer…) Recruitment of patients from GP surgeries-CBR Mobile Recruitment Unit (with thanks to Milly Apthorp Charitable Trust) Collaboration with industry (GSK, Pfizer…) Development of a National NIHR BioResource What’s next for CBR?