Accelerating haplotype-based genome-wide association study using perfect phylogeny and phase-known reference data

PLoS One. 2011;6(7):e22097. doi: 10.1371/journal.pone.0022097. Epub 2011 Jul 15.

Abstract

The genome-wide association study (GWAS) has become a routine approach for mapping disease risk loci with the advent of large-scale genotyping technologies. Multi-allelic haplotype markers can provide superior power compared with single-SNP markers in mapping disease loci. However, the application of haplotype-based analysis to GWAS is usually bottlenecked by prohibitive time cost for haplotype inference, also known as phasing. In this study, we developed an efficient approach to haplotype-based analysis in GWAS. By using a reference panel, our method accelerated the phasing process and reduced the potential bias generated by unrealistic assumptions in phasing process. The haplotype-based approach delivers great power and no type I error inflation for association studies. With only a medium-size reference panel, phasing error in our method is comparable to the genotyping error afforded by commercial genotyping solutions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Databases, Genetic / standards*
  • Genetics, Population
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / standards*
  • Haplotypes / genetics*
  • Humans
  • Phylogeny*
  • Polymorphism, Single Nucleotide / genetics
  • Reference Standards
  • Reproducibility of Results