PedBLIMP: Extending Linear Predictors to Impute Genotypes in Pedigrees

Wenan Chen, Daniel J. Schaid

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)531-541
Number of pages11
JournalGenetic epidemiology
Volume38
Issue number6
DOIs
StatePublished - Sep 1 2014

    Fingerprint

Keywords

  • Genotype imputation
  • Identity by descent
  • Linear predictor
  • Linkage disequilibrium

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Cite this