Fine-scale human genetic structure in Western France

Abstract

The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.

Figure 1

Ancestry coefficients displayed using the RGB color model. To visualize the admixture coefficient, each individual is colored using a RGB (red–green–blue) coding scheme. The RGB coefficients are proportional to the ancestry coefficients obtained with admixture. Departments of the Pays de la Loire region (bottom left). Admixture coefficients for the different regions of WF. Following the same RGB coding scheme, this figures shows the variation of admixture coefficients in WF (bottom right).

Figure 2

PCA of the CavsGen-DESIR data set. The envelopes correspond to the areas that contain 75% of the individuals of a given subdivision. (a) The envelopes correspond to the different regions of WF. Individuals from Brittany and from the Vendée and Maine-et-Loire Departments are displayed with larger crosses than the other individuals. (b) The envelopes correspond to the different departments of the Pays de la Loire Region, the Region with the majority of sampled individuals. Large crosses correspond to the barycentric coordinates of the individuals grouped by regions.

Figure 3

Mean IBS statistics between individuals from the French regions of the CavsGen-DESIR data set and individuals of POPRES from the neighboring countries of France.

Figure 4

Spatial variation of local genetic differentiation (Fst at 30 km) and of LD (at 15 kb).