A Simple and Fast Two-Locus Quality Control Test to Detect False Positives Due to Batch Effects in Genome-Wide Association Studies

作者：Lee Sang Hong^*; Nyholt Dale R; Macgregor Stuart; Henders Anjali K; Zondervan Krina T; Montgomery Grant W; Visscher Peter M

来源：Genetic Epidemiology, 2010, 34(8): 854-862.

DOI：10.1002/gepi.20541

• genome-wide association study
• batch effects
• genotyping errors
• linear model-based quality control

The impact of erroneous genotypes having passed standard quality control (QC) can be severe in genome-wide association studies, genotype imputation, and estimation of heritability and prediction of genetic risk based on single nucleotide polymorphisms (SNP). To detect such genotyping errors, a simple two-locus QC method, based on the difference in test statistic of association between single SNPs and pairs of SNPs, was developed and applied. The proposed approach could detect many problematic SNPs with statistical significance even when standard single SNP QC analyses fail to detect them in real data. Depending on the data set used, the number of erroneous SNPs that were not filtered out by standard single SNP QC but detected by the proposed approach varied from a few hundred to thousands. Using simulated data, it was shown that the proposed method was powerful and performed better than other tested existing methods. The power of the proposed approach to detect erroneous genotypes was similar to 80% for a 3% error rate per SNP. This novel QC approach is easy to implement and computationally efficient, and can lead to a better quality of genotypes for subsequent genotype-phenotype investigations. Genet. Epidemiol. 34:854-862, 2010.

• 出版日期2010-12
• 单位河北医科大学