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Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans

Nature Genetics volume 33, pages 518–521 (2003)Cite this article

Abstract

More than 5 million single-nucleotide polymorphisms (SNPs) with minor-allele frequency greater than 10% are expected to exist in the human genome1. Some of these SNPs may be associated with risk of developing common diseases2,3,4. To assess the power of currently available SNPs to detect such associations, we resequenced 50 genes in two ethnic samples and measured patterns of linkage disequilibrium between the subset of SNPs reported in dbSNP and the complete set of common SNPs. Our results suggest that using all 2.7 million SNPs currently in the database would detect nearly 80% of all common SNPs in European populations but only 50% of those common in the African American population and that efficient selection of a minimal subset of SNPs for use in association studies requires measurement of allele frequency and linkage disequilibrium relationships for all SNPs in dbSNP.

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Figure 1: Allele frequency comparison between African American and European American populations.
Figure 2: Detection of common SNPs by linkage disequilibrium using subsets of dbSNP.

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Acknowledgements

The authors would like to thank Q. Yi, T. Armel, E. Calhoun, D. Carrington, M. Chung, P. Keyes, P. Lee, C. Poel and E. Toth for producing sequence variation data for the SeattleSNPs Program for Genomic Applications and M. Lundberg and S. Banks-Schlegel for their advice and encouragement. This work was supported by a Program for Genomic Applications grant from the National Heart Lung and Blood Institute (to D.A.N., M.J.R. and L.K.) with additional support from the National Institute of Mental Health (to L.K.). L.K. is a James S. McDonnell Centennial Fellow.

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Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, 1705 NE Pacific, Seattle, 98195-7730, Washington, USA

    Christopher S. Carlson, Mark J. Rieder, Joshua D. Smith & Deborah A. Nickerson

  2. Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, 98109, Washington

    Michael A. Eberle & Leonid Kruglyak

  3. Howard Hughes Medical Institute, Chevy Chase, Maryland, USA

    Leonid Kruglyak

Authors
  1. Christopher S. Carlson
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  2. Michael A. Eberle
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  3. Mark J. Rieder
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  4. Joshua D. Smith
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  5. Leonid Kruglyak
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  6. Deborah A. Nickerson
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Corresponding authors

Correspondence to Christopher S. Carlson or Deborah A. Nickerson.

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D.A.N and L.K. consult for or own equity in companies that are interested in SNPs and association studies.

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Carlson, C., Eberle, M., Rieder, M. et al. Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nat Genet 33, 518–521 (2003). https://doi.org/10.1038/ng1128

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