The current study extends and complements other studies showing evidence of European substructure. Overall, the current results are consistent with a major north/south (or northwest/southeastern) gradient as the largest difference within European groups confirming both our previous studies and others using up to 10,000 markers and is generally consistent with much earlier studies using classic gene-frequency data [15,18]. The current results differ from previous studies in defining a northern European axis that was critically important in the case control analyses [23]. The relationship between the population groups was consistent when analysis was restricted to “northern” European population groups. As discussed further below, when more disparate populations are examined (including different “southern” populations) these relationships are not as clearly defined (see Figure 2). Thus, differences in these results compared to other studies can in part be attributed to both inclusion of different population groups and perhaps complex relationships reflecting different population origins that includes migration, admixture, and isolation. In addition, the much larger SNP set, 300K compared to maximum of 10K SNPs in previous studies, is also likely to have exposed
