Ancestral haplotype-based association mapping with generalized linear mixed models accounting for stratification

Bioinformatics. 2012 Oct 1;28(19):2467-73. doi: 10.1093/bioinformatics/bts348. Epub 2012 Jun 17.

Abstract

Motivation: In many situations, genome-wide association studies are performed in populations presenting stratification. Mixed models including a kinship matrix accounting for genetic relatedness among individuals have been shown to correct for population and/or family structure. Here we extend this methodology to generalized linear mixed models which properly model data under various distributions. In addition we perform association with ancestral haplotypes inferred using a hidden Markov model.

Results: The method was shown to properly account for stratification under various simulated scenari presenting population and/or family structure. Use of ancestral haplotypes resulted in higher power than SNPs on simulated datasets. Application to real data demonstrates the usefulness of the developed model. Full analysis of a dataset with 4600 individuals and 500 000 SNPs was performed in 2 h 36 min and required 2.28 Gb of RAM.

Availability: The software GLASCOW can be freely downloaded from www.giga.ulg.ac.be/jcms/prod_381171/software.

Contact: francois.guillaume@jouy.inra.fr

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Chromosome Mapping / methods*
  • Computational Biology / methods*
  • Computer Simulation
  • Haplotypes*
  • Linear Models*
  • Male
  • Markov Chains
  • Polymorphism, Single Nucleotide
  • Software*