Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 20, Issue 5, Pages 572-576Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2011.231
Keywords
GWAS; imputation; quality control
Funding
- Netherlands Organization for Scientific Research (NWO) [917.66.334, 175.010.2005.011, 911-03-012]
- Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007]
- Centre for Medical Systems Biology
- Netherlands Consortium for Healthy Ageing [050-060-810]
- BBMRI-NL (Biobanking and Biomolecular Resources Research Infrastructure)
- Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]
- Erasmus Medical Center
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
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Genotype imputation has become an essential tool in the analysis of genome-wide association scans. This technique allows investigators to test association at ungenotyped genetic markers, and to combine results across studies that rely on different genotyping platforms. In addition, imputation is used within long-running studies to reuse genotypes produced across generations of platforms. Typically, genotypes of controls are reused and cases are genotyped on more novel platforms yielding a case-control study that is not matched for genotyping platforms. In this study, we scrutinize such a situation and validate GWAS results by actually retyping top-ranking SNPs with the Sequenom MassArray platform. We discuss the needed quality controls (QCs). In doing so, we report a considerable discrepancy between the results from imputed and retyped data when applying recommended QCs from the literature. These discrepancies appear to be caused by extrapolating differences between arrays by the process of imputation. To avoid false positive results, we recommend that more stringent QCs should be applied. We also advocate reporting the imputation quality measure (R-T(2)) for the post-imputation QCs in publications. European Journal of Human Genetics (2012) 20, 572-576; doi:10.1038/ejhg.2011.231; published online 21 December 2011
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