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

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.

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