Etude pangénomique des effets cis haplotypiques sur l'expression des gènes dans les monocytes humains

This project aims at assessing whether gene expression variability could be influenced by the presence of more than oneproximal (eg cis-acting) single nucleotide polymorphisms (SNPs).In contrast to most previous studies looking at single SNP associations, we focused on the influence of several SNPsthrough additive or more complex haplotype combinations and undertook a systematic search of cis acting haplotypesexpression quantitative trait loci (eQTL) on the entire human genome.This strategy required the analysis of more than 2 billion haplotypic combinations. Our local cluster was not suitable to runthis project in a timely manner and large computing resources were needed. We therefore took advantage of the power ofthe European grid (EGI) to run all the statistical analyses. Our results demonstrated that the monocyte expressions of asubstantial proportion of the human genes were under the influence of multiple cis-acting SNPs. About 75% of the detectedgenetic effects were related to independent additive SNP effects and the last quarter due to more complex haplotype effects.Of note, twenty-four of the genes identified to be affected by multiple cis eSNPs have been previously reported to reside atdisease-associated loci. This could suggest that such multiple locus-specific genetic effects could contribute to thesusceptibility to human diseases