title: 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.
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] Institute of Clinical Physiology, CNR, Pisa, Italy [3] CNRS, UMR 6291 institut du thorax, Nantes, France [4] Université de Nantes, Nantes, France.
authors.forename: Matilde
authors.initials: M
authors.lastname: Karakachoff
authors.affiliation: Laboratoire TIMC-IMAG UMR 5525, Centre National de la Recherche Scientifique, Université Joseph Fourier, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duforet-Frebourg
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Simonet
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: Solena
authors.initials: S
authors.lastname: Le Scouarnec
authors.affiliation: Université de Bretagne Occidentale, Brest, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Pellen
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Lecointe
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Charpentier
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gros
authors.affiliation: 1] European Genomic Institute for Diabetes (EGID), Lille, France [2] CNRS UMR8199, Pasteur Institute of Lille, Lille, France [3] Lille Nord de France University, Lille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cauchi
authors.affiliation: 1] European Genomic Institute for Diabetes (EGID), Lille, France [2] CNRS UMR8199, Pasteur Institute of Lille, Lille, France [3] Lille Nord de France University, Lille, France [4] Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: IRSA, Institut inter-Regional pour la Santé, La Riche, France.
authors.forename: Nane
authors.initials: N
authors.lastname: Copin
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Tourneau
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Probst
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Marec
authors.affiliation: Institute of Clinical Physiology, CNR, Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Molinaro
authors.affiliation: 1] INSERM, CESP Center for Research in Epidemiology and Population Health, U1018, Villejuif, France [2] Epidemiology of diabetes, obesity and chronic kidney disease over the lifecourse, University Paris Sud 11, UMRS 1018, Villejuif, France.
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Schott
authors.affiliation: Laboratoire TIMC-IMAG UMR 5525, Centre National de la Recherche Scientifique, Université Joseph Fourier, Grenoble, France.
authors.forename: Michael Gb
authors.initials: MG
authors.lastname: Blum
authors.affiliation: 1] INSERM UMR 1087, Nantes, France [2] CNRS, UMR 6291 institut du thorax, Nantes, France [3] Université de Nantes, Nantes, France [4] CHU Nantes, l'institut du thorax, Service de Cardiologie, Nantes, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
mesh_terms: D005602:France; D015894:Genome, Human; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D043322:Lactase / Q000235:genetics; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D043322:Lactase