title: Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples.
abstract: The discordance in results of independent genome-wide association studies (GWAS) indicates the potential for Type I and Type II errors. We assessed the repeatibility of current Affymetrix technologies that support GWAS. Reasonable reproducibility was observed for both raw intensity and the genotypes/copy number variants. We also assessed consistencies between different SNP arrays and between genotype calling algorithms. We observed that the inconsistency in genotypes was generally small at the specimen level. To further examine whether the differences from genotyping and genotype calling are possible sources of variation in GWAS results, an association analysis was applied to compare the associated SNPs. We observed that the inconsistency in genotypes not only propagated to the association analysis, but was amplified in the associated SNPs. Our studies show that inconsistencies between SNP arrays and between genotype calling algorithms are potential sources for the lack of reproducibility in GWAS results.
authors.affiliation: Division of Systems Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA. huixiao.hong@fda.hhs.gov
authors.forename: H
authors.initials: H
authors.lastname: Hong
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: W
authors.initials: W
authors.lastname: Ge
authors.forename: W D
authors.initials: WD
authors.lastname: Jones
authors.forename: W
authors.initials: W
authors.lastname: Czika
authors.forename: K
authors.initials: K
authors.lastname: Miclaus
authors.forename: C G
authors.initials: CG
authors.lastname: Lambert
authors.forename: S C
authors.initials: SC
authors.lastname: Vega
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Ning
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Green
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Fang
authors.forename: R
authors.initials: R
authors.lastname: Perkins
authors.forename: S M
authors.initials: SM
authors.lastname: Lin
authors.forename: N
authors.initials: N
authors.lastname: Jafari
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: T
authors.initials: T
authors.lastname: Ahn
authors.forename: M
authors.initials: M
authors.lastname: Chierici
authors.forename: C
authors.initials: C
authors.lastname: Furlanello
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: R D
authors.initials: RD
authors.lastname: Wolfinger
authors.forename: F
authors.initials: F
authors.lastname: Goodsaid
authors.forename: W
authors.initials: W
authors.lastname: Tong
mesh_terms: D000465:Algorithms; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D018628:Gene Dosage; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D004247:DNA