title: Technical reproducibility of genotyping SNP arrays used in genome-wide association studies.
abstract: 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.
authors.affiliation: Center of Excellence for Bioinformatics, Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arizona, United States of America. huixiao.hong@fda.hhs.gov
authors.forename: Huixiao
authors.initials: H
authors.lastname: Hong
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Wendell D
authors.initials: WD
authors.lastname: Jones
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Su
authors.forename: Baitang
authors.initials: B
authors.lastname: Ning
authors.forename: Roger
authors.initials: R
authors.lastname: Perkins
authors.forename: Weigong
authors.initials: W
authors.lastname: Ge
authors.forename: Kelci
authors.initials: K
authors.lastname: Miclaus
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Park
authors.forename: Bridgett
authors.initials: B
authors.lastname: Green
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.forename: Christophe G
authors.initials: CG
authors.lastname: Lambert
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Vega
authors.forename: Simon M
authors.initials: SM
authors.lastname: Lin
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.forename: Wendy
authors.initials: W
authors.lastname: Czika
authors.forename: Russell D
authors.initials: RD
authors.lastname: Wolfinger
authors.forename: Federico
authors.initials: F
authors.lastname: Goodsaid
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
mesh_terms: D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results