Though genome-wide association studies (GWAS) have identified numerous susceptibility loci for common diseases, their use is limited due to the expense of genotyping large cohorts of individuals. One potential solution is to use ‘additional controls’, or genotype data from control individuals deposited in public repositories. While this approach has been used by several groups, the genetically heterogeneous nature of the population of the United States makes this approach potentially problematic. We empirically investigated the utility of this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New York, we observed clear population structure differences relative to controls from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS using these additional controls, we find large inflation of the test statistic that is properly corrected by using eigenvectors from principal components analysis as covariates. To deal with errors introduced due to different sources, we propose simultaneously genotyping a small number of controls along with cases and then comparing this group to the additional controls. We show that removing SNPs that show differences between these control groups reduces false-positive findings. Thus, through an empirical approach, this report provides practical guidance for using additional controls from publicly available datasets.
© 2011 S. Karger AG, Basel
- Genome-wide association studies
- Additional controls
- Population stratification
- Pancreatic cancer
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Robert J. Klein
Program in Cancer Biology and Genetics
Memorial Sloan-Kettering Cancer Center
1275 York Ave., Box 337, New York, NY 10065 (USA)
Tel. +1 646 888 2525, E-Mail firstname.lastname@example.org
Received: January 11, 2011
Accepted after revision: May 31, 2011
Published online: August 17, 2011
Number of Print Pages : 14
Number of Figures : 4, Number of Tables : 6, Number of References : 30
Additional supplementary material is available online - Number of Parts : 4
Human Heredity (International Journal of Human and Medical Genetics)
Vol. 72, No. 1, Year 2011 (Cover Date: September 2011)
Journal Editor: Devoto M. (Philadelphia, Pa./Rome)
ISSN: 0001-5652 (Print), eISSN: 1423-0062 (Online)
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