Genetic differentiation in the UK

An ASHG 2008 poster abstract on the People of the British Isles project:
The need for a well characterised UK Control Population. B. Winney, A. Boumertit, R. Bowden, D. Davison, S. Day, E. Echeta, I. Evseeva, K. Nicodemus, S. Tonks, X. Yang, P. Donnelly, W. Bodmer Dept. Clinical Pharmacology, University of Oxford, Oxford, OX3 7DQ, UK.

Until the recent advent of Whole Genome Association studies (WGAs), there were problems replicating significant associations between gene variation and complex diseases in studies that were generally underpowered. Population structure was widely considered to be the most significant reason. A powerful approach to this problem may be to characterise genetically both the cases and controls. Individuals from the controls can then be chosen to match the cases so as to minimise the stochastic differences between the two populations. Such a well-characterised control population would complement the current generation of WGAs. Importantly, the samples would be a resource that could be key to the search for rare variants that can be associated with disease susceptibility. We are assembling a UK control population as a resource for future studies. It will comprise 3,500 samples (3,200 collected so far), which will have been carefully selected from throughout the UK. Rural regions are targeted to avoid the admixture observed in large urban environments and volunteers are sought who were born in the same place as their parents and grandparents to ensure historical integrity. The collection will be genotyped for around 3,000 markers, with the aim of identifying about 200 ancestrally informative markers, which will then be used to match controls to cases. DNA from the samples will then be made available as a resource for future studies. An initial pilot project on about 400-500 samples, using a variety of markers, indicates that this approach is valid. MC1R data suggest structure differentiating the Celtic Fringe from Eastern England, whilst NRY data show evidence of Norse incursions into Orkney. Preliminary analyses of a larger pilot project, comprising about 700 samples and 400 markers, including HLA, provide further signals of population structure when all the samples are combined. There is also evidence of differentiation between some pairs of populations and simple admixture analyses suggest that there is an east-west gradient of Anglo-Saxon ancestry across England.

Going by the website, the project is now up to 3453 samples collected (out of 3500 sought). Looking forward to further results. Should shut some people up.

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