Abstract
Genome-wide association (GWA) approaches are important in complex disease gene mapping studies but are often prohibitively expensive. Array-based DNA pooling has been shown to offer substantial cost savings compared with individual genotyping. This reduced cost potentially brings well-powered GWA studies well within the reach of most laboratories. The main factor, which affects the efficiency of pooling compared with individual genotyping is the magnitude of the pooling error variance. By examining variation between and within pools it is shown that most of the error associated with pooling is attributable to array variation not pooling construction variation (assuming the pools are not small and the pools are accurately constructed). With Affymetrix HindIII 50K arrays used here the array-specific variance is seven times the pooling construction variance. This has important implications for optimal study design for array-based pooling. Given carefully constructed pools, resources should be allocated to increasing the number of arrays per sample rather than to constructing multiple pools.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Sham P, Bader JS, Craig I, O’Donovan M, Owen M : DNA pooling: a tool for large-scale association studies. Nat Rev Genet 2002; 3: 862–871.
Macgregor S, Visscher PM, Montgomery G : Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization rates. Nucleic Acids Res 2006; 34: e55.
Kirov G, Nikolov I, Georgieva L, Moskvina V, Owen MJ, O’Donovan MC : Pooled DNA genotyping on Affymetrix SNP genotyping arrays. BMC Genomics 2006; 7: 27.
Liu QR, Drgon T, Walther D et al: Pooled association genome scanning: validation and use to identify addiction vulnerability loci in two samples. Proc Natl Acad Sci USA 2005; 102: 11864–11869.
Zhao ZZ, Nyholt DR, James MR, Mayne R, Treloar SA, Montgomery GW : A comparison of DNA pools constructed following whole genome amplification for two-stage SNP genotyping designs. Twin Res Hum Genet 2005; 8: 353–361.
R Development Core Team: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2004. ISBN 3-900051-00-3.
Brohede J, Dunne R, McKay JD, Hannan GN : PPC: an algorithm for accurate estimation of SNP allele frequencies in small equimolar pools of DNA using data from high density microarrays. Nucleic Acids Res 2005; 33: e142.
Acknowledgements
Thanks to Peter M Visscher and Grant Montgomery for helpful discussions on this topic. Zhen Zhen Zhao and the QIMR Molecular and Genetic Epidemiology Laboratories provided expert assistance in collection and preparation of the DNA pools. Sue Treloar's pioneering work enabled the establishment of the QIMR Endometriosis study. The study and sample collections were partly supported by Grants 339430, 339446 and 389892 from the National Health and Medical Research Council and by the Cooperative Research Centre for the Discovery of Genes for Common Human Diseases established and supported by the Australian Government's Cooperative Research Centre's Program.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg)
Supplementary information
Rights and permissions
About this article
Cite this article
Macgregor, S. Most pooling variation in array-based DNA pooling is attributable to array error rather than pool construction error. Eur J Hum Genet 15, 501–504 (2007). https://doi.org/10.1038/sj.ejhg.5201768
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201768
Keywords
This article is cited by
-
Identification of novel alleles associated with insulin resistance in childhood obesity using pooled-DNA genome-wide association study approach
International Journal of Obesity (2018)
-
A genome-wide association study of essential hypertension in an Australian population using a DNA pooling approach
Molecular Genetics and Genomics (2017)
-
Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia
BMC Cancer (2016)
-
Pooled genome wide association detects association upstream of FCRL3 with Graves’ disease
BMC Genomics (2016)
-
GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration
Scientific Reports (2016)
