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

Z. Zhang, F. Guillaume, A. Sartelet, C. Charlier, M. Georges, F. Farnir, T. Druet
2012 Computer applications in the biosciences : CABIOS  
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
more » ... 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 data sets. Application to real data demonstrates the usefulness of the developed model. Full analysis of a data set 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
doi:10.1093/bioinformatics/bts348 pmid:22711794 fatcat:2tqovxepqveo5gvuyn5pnkh5xi