title: Influence of genotyping error in linkage mapping for complex traits--an analytic study.
abstract: BACKGROUND
  Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP) array technology in genotyping of family data has the potential to provide more informative linkage data. Nevertheless, SNP array data are not immune to genotyping error which, as has been suggested in the past, could dramatically affect the evidence for linkage especially in selective designs such as affected sib pair (ASP) designs. The influence of genotyping error on selective designs for continuous traits has not been assessed yet.
  
  
  RESULTS
  We use the identity-by-descent (IBD) regression-based paradigm for linkage testing to analytically quantify the effect of simple genotyping error models under specific selection schemes for sibling pairs. We show, for example, that in extremely concordant (EC) designs, genotyping error leads to decreased power whereas it leads to increased type I error in extremely discordant (ED) designs. Perhaps surprisingly, the effect of genotyping error on inference is most severe in designs where selection is least extreme. We suggest a genomic control for genotyping errors via a simple modification of the intercept in the regression for linkage.
  
  
  CONCLUSIONS
  This study extends earlier findings: genotyping error can substantially affect type I error and power in selective designs for continuous traits. Designs involving both EC and ED sib pairs are fairly immune to genotyping error. When those designs are not feasible the simple genomic control strategy that we suggest offers the potential to deliver more robust inference, especially if genotyping is carried out by SNP array technology.
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Postzone S-05-P, PO Box 9600 2300 RC Leiden, The Netherlands. j.j.p.lebrec@lumc.nl
authors: Jérémie J P
authors: JJ
authors: Lebrec
authors: Hein
authors: H
authors: Putter
authors: Jeanine J
authors: JJ
authors: Houwing-Duistermaat
authors: Hans C
authors: HC
authors: van Houwelingen
mesh_terms: D002874:Chromosome Mapping; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D016555:Matched-Pair Analysis; D008957:Models, Genetic; D019655:Quantitative Trait, Heritable; D012044:Regression Analysis