Significant intra-European differences at some functional alleles

From an analysis of data from a large Wisconsin medical study:

There is mounting evidence that further population stratifications may be necessary as even within a racial group there can be significant differences among people of different ancestral origin. To investigate this, we stratified our Caucasian population by self reported region of origin to determine if there were differences in allele frequencies between individuals. 11,205 (57%) individuals could be categorized by a region of origin. Using this population, there were 19 [out of 51] polymorphisms that were significantly different (p=0.05) between individuals of different origins (Table 3). Of these 5 (rs231775, rs6280, rs351855, rs601338, and rs429358) were significantly different with a p value of 0.0001 or less. Interestingly, the allele frequencies of some of the ethnic groups fell outside the 95% confidence interval of the total Caucasian MAF particularly the Eastern European ethnicity (Figure 3, Table 3). [. . .]

Because of the low number of minority racial groups in our population we chose to investigate potential substructure within only our Caucasian population. Using self reported region of ancestry, we found that 37% of the tested polymorphisms were significantly different between individuals reporting different regions of ancestry. Recent substructure analysis of Icelandic [23], Swedish[24, 36], and Ashkenazi Jewish populations [22, 37] determined that substructure was present even in these seemingly homogenous populations and that the substructure has implications for disease risk [2-5, 22-24, 36]. This study is one of the largest US studies to stratify a population by region of origin and demonstrates the large heterogeneity of the population even within a single racial group. These differences in allele frequencies may need to be considered when designing association studies in the future. One weakness of our analysis is the inability to categorize almost half (43%) of our Caucasian population into a single region of origin, because of our inability to determine the admixture given the self reported nature of the questionnaire and our limited genotyping. We are currently examining the more than 4000 individuals with whole genome scans completed to determine the ethnicities and regions of origin with greater accuracy.

[Deanna S Cross et al. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project. BMC Genetics 2010, 11:51doi:10.1186/1471-2156-11-51 17 June 2010]

And that's looking at only the following four broad, self-reported ancestries. I would expect even larger differences with the inclusion of more distant European populations.