Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples

• Published in: The pharmacogenomics journal Vol. 10; no. 4; pp. 364 - 374
• Main Authors: Hong, H, Shi, L, Su, Z, Ge, W, Jones, W D, Czika, W, Miclaus, K, Lambert, C G, Vega, S C, Zhang, J, Ning, B, Liu, J, Green, B, Xu, L, Fang, H, Perkins, R, Lin, S M, Jafari, N, Park, K, Ahn, T, Chierici, M, Furlanello, C, Zhang, L, Wolfinger, R D, Goodsaid, F, Tong, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2010; Nature Publishing Group
• Subjects: 631/1647/2217/2138; 631/208/726/649; Algorithms; Analysis; Biomedical and Life Sciences; Biomedicine; Data Interpretation, Statistical; DNA - genetics; Gene Dosage; Gene Expression; Genetic screening; Genome-Wide Association Study - statistics & numerical data; Genotype; Haplotypes - genetics; Human Genetics; Humans; Methods; Oligonucleotide Array Sequence Analysis - methods; Oncology; Original; original-article; Pharmacogenetics; Pharmacotherapy; Physiological aspects; Polymorphism, Single Nucleotide; Psychopharmacology; Reproducibility of Results; Single nucleotide polymorphisms; United States; repeatability; intensity; association; copy number; calling algorithm; genotype
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2010.24

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.