Original Article

On the follow-up of genome-wide association studies: an overall test for the most promising SNPs

  1. Peter J. Lipman1,*,
  2. Michael H. Cho2,
  3. Per Bakke3,4,
  4. Amund Gulsvik3,4,
  5. Xiangyang Kong5,
  6. David A. Lomas6,
  7. Wayne Anderson5,
  8. Edwin K. Silverman2,
  9. Christoph Lange1,2,7

Article first published online: 3 MAR 2011

DOI: 10.1002/gepi.20578

Issue

Genetic Epidemiology

Genetic Epidemiology

Volume 35, Issue 5, pages 303–309, July 2011

Additional Information

How to Cite

Lipman, P. J., Cho, M. H., Bakke, P., Gulsvik, A., Kong, X., Lomas, D. A., Anderson, W., Silverman, E. K. and Lange, C. (2011), On the follow-up of genome-wide association studies: an overall test for the most promising SNPs. Genet. Epidemiol., 35: 303–309. doi: 10.1002/gepi.20578

Author Information

  1. 1

    Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

  2. 2

    Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts

  3. 3

    Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway

  4. 4

    Institute of Medicine, University of Bergen, Bergen, Norway

  5. 5

    GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina

  6. 6

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom

  7. 7

    Institute for Genomic Mathematics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany

*Department of Biostatistics, Harvard School of Public Health, 4th Floor, Building 2, 677 Huntington Ave, Boston, MA 02115

Publication History

  1. Issue published online: 8 JUN 2011
  2. Article first published online: 3 MAR 2011
  3. Manuscript Accepted: 31 JAN 2011
  4. Manuscript Revised: 13 JAN 2011
  5. Manuscript Received: 8 SEP 2010

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Keywords:

  • genome wide association studies;
  • SNP-association tests;
  • chronic obstructive pulmonary disease;
  • statistical genetics;
  • multiple testing

Abstract

Even in large-scale genome-wide association studies (GWASs), only a fraction of the true associations are detected at the genome-wide significance level. When few or no associations reach the significance threshold, one strategy is to follow up on the most promising candidates, i.e. the single nucleotide polymorphisms (SNPs) with the smallest association-test P-values, by genotyping them in additional studies. In this communication, we propose an overall test for GWASs that analyzes the SNPs with the most promising P-values simultaneously and therefore allows an early assessment of whether the follow-up of the selected SNPs is likely promising. We theoretically derive the properties of the proposed overall test under the null hypothesis and assess its power based on simulation studies. An application to a GWAS for chronic obstructive pulmonary disease suggests that there are true association signals among the top SNPs and that an additional follow-up study is promising. Genet. Epidemiol. 2011.   © 2011 Wiley-Liss, Inc. 35:303-309, 2011

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