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Link to original content: https://pubmed.ncbi.nlm.nih.gov/17572673/
A new multipoint method for genome-wide association studies by imputation of genotypes - PubMed Skip to main page content
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. 2007 Jul;39(7):906-13.
doi: 10.1038/ng2088. Epub 2007 Jun 17.

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

Jonathan Marchini  1 , Bryan Howie, Simon Myers, Gil McVean, Peter Donnelly
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A new multipoint method for genome-wide association studies by imputation of genotypes

Jonathan Marchini et al. Nat Genet. 2007 Jul.

Abstract

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.

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