Investigation of the fine structure of European populations with applications to disease association studies

Simon C. Heath, Ivo G. Gut, Paul Brennan, James D. McKay, Vladimir Bencko, Eleonora Fabianova, Lenka Foretova, Michael Georges, Vladimir Janout, Michael Kabesch, Hans E. Krokan, Maiken B. Elvestad, Jolanta Lissowska, Dana Mates, Peter Rudnai, Frank Skorpen, Stefan Schreiber, José M. Soria, Ann Christine Syvänen, Pierre MenetonSerge Herçberg, Pilar Galan, Neonilia Szeszenia-Dabrowska, David Zaridze, Emmanuel Génin, Lon R. Cardon, Mark Lathrop

Research output: Contribution to journalArticle

127 Citations (Scopus)

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 300000 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.

Original languageEnglish
Pages (from-to)1413-1429
Number of pages17
JournalEuropean Journal of Human Genetics
Volume16
Issue number12
DOIs
Publication statusPublished - Jan 1 2008

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Heath, S. C., Gut, I. G., Brennan, P., McKay, J. D., Bencko, V., Fabianova, E., Foretova, L., Georges, M., Janout, V., Kabesch, M., Krokan, H. E., Elvestad, M. B., Lissowska, J., Mates, D., Rudnai, P., Skorpen, F., Schreiber, S., Soria, J. M., Syvänen, A. C., ... Lathrop, M. (2008). Investigation of the fine structure of European populations with applications to disease association studies. European Journal of Human Genetics, 16(12), 1413-1429. https://doi.org/10.1038/ejhg.2008.210