title: Accelerating haplotype-based genome-wide association study using perfect phylogeny and phase-known reference data.
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.
authors.affiliation: Department of Computational Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. heyungang@gmail.com
authors.forename: Yungang
authors.initials: Y
authors.lastname: He
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Momiao
authors.initials: M
authors.lastname: Xiong
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Li
authors.initials: L
authors.lastname: Jin
mesh_terms: D003198:Computer Simulation; D030541:Databases, Genetic / Q000592:standards*; D005828:Genetics, Population; D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012015:Reference Standards; D015203:Reproducibility of Results