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An Icelandic example of the impact of population structure on association studies

Nature Genetics 37, 90–95 (2005) | Download Citation

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Abstract

The impact of population structure on association studies undertaken to identify genetic variants underlying common human diseases is an issue of growing interest1,2,3,4. Spurious associations of alleles with disease phenotypes may be obtained or true associations overlooked when allele frequencies differ notably among subpopulations that are not represented equally among cases and controls. Population structure influences even carefully designed studies and can affect the validity of association results1,2. Most study designs address this problem by sampling cases and controls from groups that share the same nationality or self-reported ethnic background, with the implicit assumption that no substructure exists within such groups. We examined population structure in the Icelandic gene pool using extensive genealogical and genetic data. Our results indicate that sampling strategies need to take account of substructure even in a relatively homogenous5 genetic isolate6. This will probably be even more important in larger populations.

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Acknowledgements

We thank P. Donnelly and D. Altshuler for comments on a previous version of this paper.

Author information

Affiliations

  1. deCODE Genetics, Sturlugata 8, 101 Reykjavík, Iceland.

    • Agnar Helgason
    • , Bryndís Yngvadóttir
    • , Birgir Hrafnkelsson
    • , Jeffrey Gulcher
    •  & Kári Stefánsson

  2. University of Iceland, 101 Reykjavík, Iceland.

    • Bryndís Yngvadóttir
    •  & Birgir Hrafnkelsson

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Competing interests

A.H., J.G. and K.S. have stocks or equity interests in deCODE Genetics.

Corresponding author

Correspondence to Agnar Helgason.

Supplementary information

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  1. 1.

    Supplementary Fig. 1

    Genetic divergence measured by the c parameter among 11 subpopulations for three cohorts of genotypes.

  2. 2.

    Supplementary Table 1

    Descriptive statistics for the 40 microsatellite loci used in the genetic analyses of population structure.

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DOI

https://doi.org/10.1038/ng1492

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