1. ¹Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France
2. ²International Agency for Research on Cancer (IARC), Lyon, France
3. ³First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic
4. ⁴Specialized Institute of Hygiene and Epidemiology, Banska Bystrica, Slovakia
5. ⁵Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
6. ⁶Unit of Animal Genomics, Faculty of Veterinary Medicine, GIGA-Research and Department of Animal Sciences, University of Liège, Liège, Belgium
7. ⁷Department of Preventive Medicine, Palacky University, Olomouc, Czech Republic
8. ⁸University Children's Hospital, Ludwig Maximilian's University Munich, Munich, Germany
9. ⁹Faculty of Medicine, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
10. ¹⁰M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
11. ¹¹Institute of Public Health, Bucharest, Romania
12. ¹²National Institute of Environmental Health, Budapest, Hungary
13. ¹³Faculty of Medicine, Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
14. ¹⁴Institute for Clinical Molecular Biology, PopGen biobank, Christian-Albrechts-University, Kiel, Germany
15. ¹⁵Unitat de Genómica de Malaties Complexes, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, C/Sant Antoni M^a Claret, 167, Barcelona, Spain
16. ¹⁶Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
17. ¹⁷INSERM U872, Centre de Recherche des Cordeliers, Paris, France
18. ¹⁸INSERM U557 et Unité de Recherche de Epidémiologie Nutritionnelle, 74 rue Marcel Cachin, Bobigny Cedex, France
19. ¹⁹Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland
20. ²⁰Cancer Research Centre, Institute of Carcinogenesis, Moscow, Russia
21. ²¹INSERM U794, Fondation Jean Dausset-CEPH, Paris, France
22. ²²GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania, USA
23. ²³Fondation Jean Dausset-CEPH, Paris, France

Correspondence: Dr SC Heath, Centre National de Génotypage, 2, Rue Gaston Crémieux, 154 rue du Fbg. St Denis, Evry 91000, France. Tel: +160878402; Fax: +160878485; E-mail: simon.heath@gmail.com

Received 8 August 2008; Revised 8 October 2008; Accepted 9 October 2008.

Abstract

An investigation into fine-scale European population structure was carried out using high-density genetic variation on nearly 6000 individuals originating from across Europe. The individuals were collected as control samples and were genotyped with more than 300 000 SNPs in genome-wide association studies using the Illumina Infinium platform. A major East–West gradient from Russian (Moscow) samples to Spanish samples was identified as the first principal component (PC) of the genetic diversity. The second PC identified a North–South gradient from Norway and Sweden to Romania and Spain. Variation of frequencies at markers in three separate genomic regions, surrounding LCT, HLA and HERC2, were strongly associated with this gradient. The next 18 PCs also accounted for a significant proportion of genetic diversity observed in the sample. We present a method to predict the ethnic origin of samples by comparing the sample genotypes with those from a reference set of samples of known origin. These predictions can be performed using just summary information on the known samples, and individual genotype data are not required. We discuss issues raised by these data and analyses for association studies including the matching of case-only cohorts to appropriate pre-collected control samples for genome-wide association studies.