An Icelandic example of the impact of population structure on association studies.
paper
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- Authors
- Helgason, Agnar; Yngvadóttir, Bryndís; Hrafnkelsson, Birgir; Gulcher, Jeffrey; Stefánsson, Kári
- Year
- 2005
- Journal
- Nature genetics
- PMID
- 15608637
- DOI
- 10.1038/ng1492
The impact of population structure on association studies undertaken to identify genetic variants underlying common human diseases is an issue of growing interest. 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 results. 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 homogenous genetic isolate. This will probably be even more important in larger populations.
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