The effects of human population structure on large genetic association studies - PubMed (original) (raw)
doi: 10.1038/ng1337. Epub 2004 Mar 28.
Affiliations
- PMID: 15052271
- DOI: 10.1038/ng1337
The effects of human population structure on large genetic association studies
Jonathan Marchini et al. Nat Genet. 2004 May.
Abstract
Large-scale association studies hold substantial promise for unraveling the genetic basis of common human diseases. A well-known problem with such studies is the presence of undetected population structure, which can lead to both false positive results and failures to detect genuine associations. Here we examine approximately 15,000 genome-wide single-nucleotide polymorphisms typed in three population groups to assess the consequences of population structure on the coming generation of association studies. The consequences of population structure on association outcomes increase markedly with sample size. For the size of study needed to detect typical genetic effects in common diseases, even the modest levels of population structure within population groups cannot safely be ignored. We also examine one method for correcting for population structure (Genomic Control). Although it often performs well, it may not correct for structure if too few loci are used and may overcorrect in other settings, leading to substantial loss of power. The results of our analysis can guide the design of large-scale association studies.
Comment in
- Genomic Control to the extreme.
Devlin B, Bacanu SA, Roeder K. Devlin B, et al. Nat Genet. 2004 Nov;36(11):1129-30; author reply 1131. doi: 10.1038/ng1104-1129. Nat Genet. 2004. PMID: 15514657 No abstract available.
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