Computational protocol: Genetic Variation at the FTO Locus Influences RBL2 Gene Expression

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Protocol publication

[…] Multivariate methods generally require that individuals with missing data be excluded from the analysis, which can result in a significant decrease in sample size. To minimize this issue, we used likelihood-based imputation with the MERLIN computer package as has been previously described () to rapidly impute SNP data in pedigrees. For each pedigree, imputation is performed and the posterior genotypic probabilities for each missing genotype are stored. These posterior probabilities are used to construct an appropriately weighted covariate for each SNP that is then used in association analyses.To eliminate the potential for hidden population stratification that the standard fixed-effect association approach is susceptible to, we also used the quantitative transmission disequilibrium test approach to association testing implemented in SOLAR (). Although this approach exhibits substantially decreased power than measured genotype analysis (), it maintains the appropriate significance levels under the null hypothesis, even in the presence of population stratification. However, because of its poor power, we used it only as a check to identify consistence of qualitative inferences drawn from measured genotype analysis. […]

Pipeline specifications

Software tools merlin, IMPUTE
Application GWAS
Organisms Homo sapiens
Diseases Diabetes Mellitus