People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population

Abstract

There is a great deal of interest in a fine-scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to have a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. In this study, we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK-control population that can be used as a resource by the research community, as well as providing a fine-scale genetic information on the British population. So far, some 4000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3 km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1057 samples demonstrates the value of these samples for investigating a fine-scale population structure within the UK, and shows how this can be enhanced by the use of surnames.

Figure 1

Graph of the log (MLQ) of the RD with the highest LQ for each surname (y-axis) against log (surname population size) in the 1881 census (x-axis). There are a number of surnames (circled) with a higher MLQ than might be expected for the surname sample size (Jones, Davies, Evans, Thomas, Hughes, James and Phillips), which are established Welsh surnames. The surnames from Supplementary Figure 1 are also marked.

Figure 2

Distribution of MGP of grandparental birthplaces of the 3646 volunteers for whom there was information for all four grandparents. Dots mark the MPG for individual volunteers. The populations from which samples were taken for the genotyping are marked on the inset map.

Figure 3

Percentage of volunteers with all four grandparents classed as rural according to their distance (2, 5 or 10 km) from an urban area (y axis) of a given population size (x-axis). Estimates are made for all the geocoded samples (all samples) and those genotyped (pilot samples).