Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays.

@article{citeulike:2437401, abstract = {Genome-wide association (GWA) studies to map genes for complex traits are powerful yet costly. DNA-pooling strategies have the potential to dramatically reduce the cost of GWA studies. Pooling using Affymetrix arrays has been proposed and used but the efficiency of these arrays has not been quantified. We compared and contrasted Affymetrix Genechip HindIII and Illumina HumanHap300 arrays on the same DNA pools and showed that the HumanHap300 arrays are substantially more efficient. In terms of effective sample size, HumanHap300-based pooling extracts >80\% of the information available with individual genotyping (IG). In contrast, Genechip HindIII-based pooling only extracts approximately 30\% of the available information. With HumanHap300 arrays concordance with IG data is excellent. Guidance is given on best study design and it is shown that even after taking into account pooling error, one stage scans can be performed for >100-fold reduced cost compared with IG. With appropriately designed two stage studies, IG can provide confirmation of pooling results whilst still providing approximately 20-fold reduction in total cost compared with IG-based alternatives. The large cost savings with Illumina HumanHap300-based pooling imply that future studies need only be limited by the availability of samples and not cost.}, address = {Genetic Epidemiology, Queensland Institute of Medical Research and Molecular Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia.}, author = {Macgregor, Stuart and Zhao, Zhen Zhen Z. and Henders, Anjali and Nicholas, Martin G G. and Montgomery, Grant W W. and Visscher, Peter M M. }, citeulike-article-id = {2437401}, doi = {10.1093/nar/gkm1060}, issn = {1362-4962}, journal = {Nucleic Acids Res}, keywords = {gwa, microarray, pooling}, month = {February}, posted-at = {2008-02-27 15:57:37}, priority = {4}, title = {Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays.}, url = {http://dx.doi.org/10.1093/nar/gkm1060}, year = {2008} }

TY - JOUR ID - citeulike:2437401 L3 - citeulike-article-id:2437401 TI - Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays. JF - Nucleic Acids Res AD - Genetic Epidemiology, Queensland Institute of Medical Research and Molecular Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia. SN - 1362-4962 N2 - Genome-wide association (GWA) studies to map genes for complex traits are powerful yet costly. DNA-pooling strategies have the potential to dramatically reduce the cost of GWA studies. Pooling using Affymetrix arrays has been proposed and used but the efficiency of these arrays has not been quantified. We compared and contrasted Affymetrix Genechip HindIII and Illumina HumanHap300 arrays on the same DNA pools and showed that the HumanHap300 arrays are substantially more efficient. In terms of effective sample size, HumanHap300-based pooling extracts >80% of the information available with individual genotyping (IG). In contrast, Genechip HindIII-based pooling only extracts approximately 30% of the available information. With HumanHap300 arrays concordance with IG data is excellent. Guidance is given on best study design and it is shown that even after taking into account pooling error, one stage scans can be performed for >100-fold reduced cost compared with IG. With appropriately designed two stage studies, IG can provide confirmation of pooling results whilst still providing approximately 20-fold reduction in total cost compared with IG-based alternatives. The large cost savings with Illumina HumanHap300-based pooling imply that future studies need only be limited by the availability of samples and not cost. KW - gwa KW - microarray KW - pooling AU - Macgregor, Stuart AU - Zhao, Zhen Zhen AU - Henders, Anjali AU - Nicholas, Martin G AU - Montgomery, Grant W AU - Visscher, Peter M PY - 2008/02/14/ UR - http://dx.doi.org/10.1093/nar/gkm1060 ER -