Investigation of the fine structure of European populations with applications to disease association studies") finds 11 of these 13 SNPs are also "involved in East–West and North–South gradients covering all of Europe".Thirteen genomic regions showing strong geographical variation are listed in Table 1, and Supplementary Fig. 7 shows the way in which their allele frequencies vary geographically. The predominant pattern is variation along a NW/SE axis. The most likely cause for these marked geographical differences is natural selection, most plausibly in populations ancestral to those now in the UK. Variation due to selection has previously been implicated at LCT (lactase) and major histocompatibility complex(MHC)7–9, and within-UK differentiation at 4p14 has been found independently10, but others seem to be new findings. All but three of the regions contain known genes. Aside from evolutionary interest, genes showing evidence of natural selection are particularly interesting for the biology of traits such as infectious diseases; possible targets for selection include NADSYN1 (NAD synthetase 1) at 11q13, which could have a role in prevention of pellagra, as well as TLR1 (toll-like receptor 1) at 4p14, for which a role in the biology of tuberculosis and leprosy has been suggested10.
There may be important population structure that is not well captured by current geographical region of residence. Present implementations of strongly model-based approaches such as STRUCTURE11,12 are impracticable for data sets of this size, and we reverted to the classical method of principal components13,14, using a subset of 197,175 SNPs chosen to reduce inter-locus linkage disequilibrium. Nevertheless, four of the first six principal components clearly picked up effects attributable to local linkage disequilibrium rather than genome-wide structure. The remaining two components show the same predominant geographical trend from NW to SE but, perhaps unsurprisingly, London is set somewhat apart (Supplementary Fig. 8).
[The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (7 June 2007) | doi:10.1038/nature05911]
Related: Genetic differentiation in the UK