Quality control and quality assurance in genotypic data for genome-wide association studies

Cathy C. Laurie, Kimberly F. Doheny, Daniel B. Mirel, Elizabeth W. Pugh, Laura J. Bierut, Tushar Bhangale, Frederick Boehm, Neil E. Caporaso, Marilyn C. Cornelis, Howard J. Edenberg, Stacy B. Gabriel, Emily L. Harris, Frank B. Hu, Kevin B. Jacobs, Peter Kraft, Maria Teresa Landi, Thomas Lumley, Teri A. Manolio, Caitlin McHugh, Ian PainterJustin Paschall, John P. Rice, Kenneth M. Rice, Xiuwen Zheng, Bruce S. Weir

Research output: Contribution to journalArticlepeer-review

344 Scopus citations


Genome-wide scans of nucleotide variation in human subjects are providing an increasing number of replicated associations with complex disease traits. Most of the variants detected have small effects and, collectively, they account for a small fraction of the total genetic variance. Very large sample sizes are required to identify and validate findings. In this situation, even small sources of systematic or random error can cause spurious results or obscure real effects. The need for careful attention to data quality has been appreciated for some time in this field, and a number of strategies for quality control and quality assurance (QC/QA) have been developed. Here we extend these methods and describe a system of QC/QA for genotypic data in genome-wide association studies (GWAS). This system includes some new approaches that (1) combine analysis of allelic probe intensities and called genotypes to distinguish gender misidentification from sex chromosome aberrations, (2) detect autosomal chromosome aberrations that may affect genotype calling accuracy, (3) infer DNA sample quality from relatedness and allelic intensities, (4) use duplicate concordance to infer SNP quality, (5) detect genotyping artifacts from dependence of Hardy-Weinberg equilibrium test P-values on allelic frequency, and (6) demonstrate sensitivity of principal components analysis to SNP selection. The methods are illustrated with examples from the "Gene Environment Association Studies" (GENEVA) program. The results suggest several recommendations for QC/QA in the design and execution of GWAS.

Original languageEnglish
Pages (from-to)591-602
Number of pages12
JournalGenetic Epidemiology
Issue number6
StatePublished - Sep 2010


  • Chromosome aberration
  • DNA sample quality
  • GWAS
  • Genotyping artifact
  • Hardy-Weinberg equilibrium


Dive into the research topics of 'Quality control and quality assurance in genotypic data for genome-wide association studies'. Together they form a unique fingerprint.

Cite this