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.
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Acknowledgements
We thank Emmanuelle Bourcereau who was involved in patient recruitment of the CavsGen cohort. We also thank Professors Le Guerrier and Baufreton from University Hospitals of Rennes and Angers. We are grateful to the French Regional Council of Pays-de-la-Loire (Regional grant Biliv, grant VACARME - www.vacarme-project.org), the French Ministry of Health (PHRC/RNI-PROG/09/61: Génétique du rétrécissement aortique) and the French Ministry of Research (CavsGen project, ANR-13-BSV6-0011-01). We wish to thank the Fondation Genavie for its financial support. The POPRES data were obtained from dbGaP (accession no. phs000145.v3.p2). FS was funded by a Eurostars E!6490 Cardiomarks grant. MGBB is supported by the French National Research Agency (DATGEN project, ANR-2010-JCJC-1607-01). The D.E.S.I.R. study has been supported by INSERM contracts with CNAMTS, Lilly, Novartis Pharma and Sanofi-Aventis; by INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé), Cohortes Santé TGIR, the Association Diabète Risque Vasculaire, the Fédération Française de Cardiologie, La Fondation de France, ALFEDIAM, Société francophone du diabète, ONIVINS, Abbott, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche, Topcon.
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The D.E.S.I.R. Study Group INSERM U1018: B Balkau, P Ducimetière, E Eschwège; INSERM U367: F Alhenc-Gelas; CHU D’Angers: A Girault; Bichat Hospital: F Fumeron, M Marre, R Roussel; CHU de Rennes: F. Bonnet; CNRS UMR8090, Lille: S Cauchi, P Froguel; Centres d’Examens de Santé: Alençon, Angers, Blois, Caen, Chateauroux, Chartres, Cholet, Le Mans, Orléans, Tours; Institute de Recherche Médecine Générale: J Cogneau; General practitioners of the Region; Institute inter-Regional pour la Santé: C Born, E Caces, M Cailleau, O Lantieri, JG Moreau, F Rakotozafy, J Tichet, S Vol.
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Karakachoff, M., Duforet-Frebourg, N., Simonet, F. et al. Fine-scale human genetic structure in Western France. Eur J Hum Genet 23, 831–836 (2015). https://doi.org/10.1038/ejhg.2014.175
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DOI: https://doi.org/10.1038/ejhg.2014.175
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