comparing methods for mapping cis acting polymorphisms using allelic expression ratios比较的方法映射cis代理使用等位基因多态性表达比率.pdfVIP

Comparing Methods for Mapping cis Acting Polymorphisms Using Allelic Expression Ratios 1 1,2 3 4 Marion Dawn Teare *, Suteeraporn Pinyakorn , James Heighway , Mauro F. Santibanez Koref 1 School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom, 2 The HIV Netherlands Australia Thailand Research Collaboration, Pathumwan, Bangkok, Thailand, 3 Cancer Communications and Consultancy Ltd, Knutsford, Cheshire, United Kingdom, 4 Institute of Human Genetics, University of Newcastle, Newcastle upon Tyne, United Kingdom Abstract Genome wide association studies frequently reveal associations between disease susceptibility and polymorphisms outside coding regions. Such associations cannot always be explained by linkage disequilibrium with changes affecting the transcription products. This has stimulated the interest in characterising sequence variation influencing gene expression levels, in particular in changes acting in cis. Differences in transcription between the two alleles at an autosomal locus can be used to test the association between candidate polymorphisms and the modulation of gene expression in cis. This type of approach requires at least one transcribed polymorphism and one candidate polymorphism. In the past five years, different methods have been proposed to analyse such data. Here we use simulations and real data sets to compare the power of some of these methods. The results show that when it is not possible to determine the phase between the transcribed and potentially cis acting allele there is some advantage in using methods that estimate phased genotype and effect on exp