PedBLIMP: Extending Linear Predictors to Impute Genotypes in Pedigrees

Recently, Wen and Stephens (Wen and Stephens [2010] Ann Appl Stat 4(3):1158–1182) proposed a linear predictor, called BLIMP, that uses conditional multivariate normal moments to impute genotypes with accuracy similar to current state‐of‐the‐art methods. One novelty is that it regularized the estimated covariance matrix based on a model from population genetics. We extended multivariate moments to impute genotypes in pedigrees. Our proposed method, PedBLIMP, utilizes both the linkage‐disequilibrium (LD) information estimated from external panel data and the pedigree structure or identity‐by‐descent (IBD) information. The proposed method was evaluated on a pedigree design where some individuals were genotyped with dense markers and the rest with sparse markers. We found that incorporating the pedigree/IBD information can improve imputation accuracy compared to BLIMP. Because rare variants usually have low LD with other single‐nucleotide polymorphisms (SNPs), incorporating pedigree/IBD information largely improved imputation accuracy for rare variants. We also compared PedBLIMP with IMPUTE2 and GIGI. Results show that when sparse markers are in a certain density range, our method can outperform both IMPUTE2 and GIGI.

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