A simple and fast two-locus quality control test to detect false positives due to batch effects in genome-wide association studies

Sang Hong Lee, Dale R. Nyholt, Stuart Macgregor, Anjali K. Henders, Krina T. Zondervan, Grant W. Montgomery, Peter M. Visscher

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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 ~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.

Original languageEnglish
Pages (from-to)854-862
Number of pages9
JournalGenetic Epidemiology
Issue number8
Publication statusPublished or Issued - Dec 2010
Externally publishedYes


  • Batch effects
  • Genome-wide association study
  • Genotyping errors
  • Linear model-based quality control

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Cite this