Data quality control in genetic case-control association studies

• Published in: Nature protocols Vol. 5; no. 9; pp. 1564 - 1573
• Main Authors: Anderson, Carl A, Pettersson, Fredrik H, Clarke, Geraldine M, Cardon, Lon R, Morris, Andrew P, Zondervan, Krina T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2010; Nature Publishing Group
• Subjects: 631/114/1767; 631/114/794; 631/1647/2217/2138; Algorithms; Analytical Chemistry; Animals; Applications software; Biological Techniques; Case studies; Case-Control Studies; Computational Biology - methods; Computational Biology/Bioinformatics; Control data (computers); Data analysis; Deoxyribonucleic acid; Disease control; DNA; Failure rates; Female; Genetic research; Genetic Techniques; Genome-Wide Association Study - methods; Genomes; Genotype & phenotype; Humans; Life Sciences; Male; Management; Methods; Microarrays; Organic Chemistry; Outliers (statistics); protocol; Quality assessment; Quality Control; Quality management; Single-nucleotide polymorphism; Software; United States; United Kingdom > UK
• ISSN: 1754-2189; 1750-2799; 1750-2799
• DOI: 10.1038/nprot.2010.116

This protocol details the steps for data quality assessment and control that are typically carried out during case-control association studies. The steps described involve the identification and removal of DNA samples and markers that introduce bias. These critical steps are paramount to the success of a case-control study and are necessary before statistically testing for association. We describe how to use PLINK, a tool for handling SNP data, to perform assessments of failure rate per individual and per SNP and to assess the degree of relatedness between individuals. We also detail other quality-control procedures, including the use of SMARTPCA software for the identification of ancestral outliers. These platforms were selected because they are user-friendly, widely used and computationally efficient. Steps needed to detect and establish a disease association using case-control data are not discussed here. Issues concerning study design and marker selection in case-control studies have been discussed in our earlier protocols. This protocol, which is routinely used in our labs, should take approximately 8 h to complete.