TY - JOUR
T1 - Technical Reproducibility of Genotyping SNP Arrays Used in Genome-Wide Association Studies
AU - Hong, Huixiao
AU - Xu, Lei
AU - Liu, Jie
AU - Jones, Wendell D.
AU - Su, Zhenqiang
AU - Ning, Baitang
AU - Perkins, Roger
AU - Ge, Weigong
AU - Miclaus, Kelci
AU - Zhang, Li
AU - Park, Kyunghee
AU - Green, Bridgett
AU - Han, Tao
AU - Fang, Hong
AU - Lambert, Christophe G.
AU - Vega, Silvia C.
AU - Lin, Simon M.
AU - Jafari, Nadereh
AU - Czika, Wendy
AU - Wolfinger, Russell D.
AU - Goodsaid, Federico
AU - Tong, Weida
AU - Shi, Leming
PY - 2012/9/7
Y1 - 2012/9/7
N2 - During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. Moreover, discordance observed in results between independent GWAS indicates the potential for Type I and II errors. High reliability of genotyping technology is needed to have confidence in using SNP data and interpreting GWAS results. Therefore, reproducibility of two widely genotyping technology platforms from Affymetrix and Illumina was assessed by analyzing four technical replicates from each of the six individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within a laboratory for the sample platform, 98.59% to 99.86% across laboratories for the same platform, and 98.80% across genotyping platforms was observed. Moreover, arrays with low quality data were detected when comparing genotyping data from technical replicates, but they could not be detected according to venders' quality control (QC) suggestions. Our results demonstrated the technical reliability of currently available genotyping platforms but also indicated the importance of incorporating some technical replicates for genotyping QC in order to improve the reliability of GWAS results. The impact of discordant genotypes on association analysis results was simulated and could explain, at least in part, the irreproducibility of some GWAS findings when the effect size (i.e. the odds ratio) and the minor allele frequencies are low.
AB - During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. Moreover, discordance observed in results between independent GWAS indicates the potential for Type I and II errors. High reliability of genotyping technology is needed to have confidence in using SNP data and interpreting GWAS results. Therefore, reproducibility of two widely genotyping technology platforms from Affymetrix and Illumina was assessed by analyzing four technical replicates from each of the six individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within a laboratory for the sample platform, 98.59% to 99.86% across laboratories for the same platform, and 98.80% across genotyping platforms was observed. Moreover, arrays with low quality data were detected when comparing genotyping data from technical replicates, but they could not be detected according to venders' quality control (QC) suggestions. Our results demonstrated the technical reliability of currently available genotyping platforms but also indicated the importance of incorporating some technical replicates for genotyping QC in order to improve the reliability of GWAS results. The impact of discordant genotypes on association analysis results was simulated and could explain, at least in part, the irreproducibility of some GWAS findings when the effect size (i.e. the odds ratio) and the minor allele frequencies are low.
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U2 - 10.1371/journal.pone.0044483
DO - 10.1371/journal.pone.0044483
M3 - Article
C2 - 22970228
AN - SCOPUS:84866081687
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 9
M1 - e44483
ER -