title: MixupMapper: correcting sample mix-ups in genome-wide datasets increases power to detect small genetic effects.
abstract: BACKGROUND
  Sample mix-ups can arise during sample collection, handling, genotyping or data management. It is unclear how often sample mix-ups occur in genome-wide studies, as there currently are no post hoc methods that can identify these mix-ups in unrelated samples. We have therefore developed an algorithm (MixupMapper) that can both detect and correct sample mix-ups in genome-wide studies that study gene expression levels.
  
  
  RESULTS
  We applied MixupMapper to five publicly available human genetical genomics datasets. On average, 3% of all analyzed samples had been assigned incorrect expression phenotypes: in one of the datasets 23% of the samples had incorrect expression phenotypes. The consequences of sample mix-ups are substantial: when we corrected these sample mix-ups, we identified on average 15% more significant cis-expression quantitative trait loci (cis-eQTLs). In one dataset, we identified three times as many significant cis-eQTLs after correction. Furthermore, we show through simulations that sample mix-ups can lead to an underestimation of the explained heritability of complex traits in genome-wide association datasets.
  
  
  METHODS
  MixupMapper is freely available at http://www.genenetwork.nl/mixupmapper/
authors.affiliation: Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Westra
authors.forename: Ritsert C
authors.initials: RC
authors.lastname: Jansen
authors.forename: Rudolf S N
authors.initials: RS
authors.lastname: Fehrmann
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: David
authors.initials: D
authors.lastname: van Heel
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012680:Sensitivity and Specificity; D013048:Specimen Handling