A new multipoint method for genome-wide association studies by imputation of genotypes

Nat Genet. 2007 Jul;39(7):906-13. doi: 10.1038/ng2088. Epub 2007 Jun 17.


Genome-wide association studies are set to become the method of choice for uncovering the genetic basis of human diseases. A central challenge in this area is the development of powerful multipoint methods that can detect causal variants that have not been directly genotyped. We propose a coherent analysis framework that treats the problem as one involving missing or uncertain genotypes. Central to our approach is a model-based imputation method for inferring genotypes at observed or unobserved SNPs, leading to improved power over existing methods for multipoint association mapping. Using real genome-wide association study data, we show that our approach (i) is accurate and well calibrated, (ii) provides detailed views of associated regions that facilitate follow-up studies and (iii) can be used to validate and correct data at genotyped markers. A notable future use of our method will be to boost power by combining data from genome-wide scans that use different SNP sets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Case-Control Studies
  • Genetic Markers
  • Genetics, Population
  • Genome, Human*
  • Genomics / statistics & numerical data*
  • Genotype
  • Humans
  • Models, Genetic
  • Polymorphism, Single Nucleotide


  • Genetic Markers