title: SEQCHIP: a powerful method to integrate sequence and genotype data for the detection of rare variant associations.
abstract: BACKGROUND
  Next-generation sequencing greatly increases the capacity to detect rare-variant complex-trait associations. However, it is still expensive to sequence a large number of samples and therefore often small datasets are used. Given cost constraints, a potentially more powerful two-step strategy is to sequence a subset of the sample to discover variants, and genotype the identified variants in the remaining sample. If only cases are sequenced, directly combining sequence and genotype data will lead to inflated type-I errors in rare-variant association analysis. Although several methods have been developed to correct for the bias, they are either underpowered or theoretically invalid. We proposed a new method SEQCHIP to integrate genotype and sequence data, which can be used with most existing rare-variant tests.
  
  
  RESULTS
  It is demonstrated using both simulated and real datasets that the SEQCHIP method has controlled type-I errors, and is substantially more powerful than all other currently available methods.
  
  
  BACKGROUND
  SEQCHIP is implemented in an R-Package and is available at http://linkage.rockefeller.edu/suzanne/seqchip/Seqchip.html.
authors.affiliation: Department of Biostatistics, Center of Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA. dajiang@umich.edu
authors.forename: Dajiang J
authors.initials: DJ
authors.lastname: Liu
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
mesh_terms: D000236:Adenoma / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software