Elucidating the relationship between changes in genotype and expression dynamics, which will promote the understanding of the results of GWAS. eQTL information provides insights into the regulation of transcription and aids in the interpretation of genome-wide association studies. In cases in which the allelic changes of a SNP are significantly correlated with the expression of a gene, the SNP is defined as an eQTL-SNP. Using this information, researchers try to identify trait-associated SNPs that would be otherwise hard to find. For example, Fransen and colleagues reported a GWAS for Crohn’s disease using eQTL-SNP information. Those authors selected eQTL SNPs among the GWAS results for Crohn’s disease, and performed follow-up replication studies. They showed that the eQTL-based preselection for follow-up studies was a useful approach for identifying risk loci from the results of a moderately sized GWAS. Here, we reanalyzed genome-wide associations between metabolic traits and SNPs using eQTL information.Extra-hematopoietic compartments are protected from weight loss, as demonstrated previously, as well as crypt damage in response to DSS. Furthermore, we demonstrate mice with WT bone marrow exhibited significantly more neutrophilia following DSS-induced colitis, suggesting that hematopoietic-derived SK1/S1P are necessary for the recruitment of specific immune cells in circulation and are a critical part of the systemic inflammatory response. Our data also demonstrate that specific cytokines, as well as STAT3 activation, require SK1/S1P from both hematopoietic and extra-hematopoietic sources in acute DSS-induced colitis. Additionally, we show here that extra-hematopoietic SK1/S1P is necessary for the induction of COX2 in the colon epithelium in response to DSS. Taken together these data suggest that SK1/S1P play critical and distinct roles in both systemic and local inflammatory responses in DSS-induced colitis. In this study we observed a basal increase in spleen size in mice lacking hematopoietic SK1, irrespective of tissue genotype. Moreover, both SK1SK1BM and WTSK1BM mice demonstrated larger spleens following DSS. Previously we demonstrated that total body loss of SK1 increased basal spleen weight; however, mice lacking SK1 failed to exhibit splenomegaly as WT mice did when challenged with DSS. Interestingly, several studies in lymphocyte egress and trafficking have also demonstrated that hematopoietic sources of S1P are necessary for egress of lymphocytes from the spleen in mice deficient in both isoforms of SK. Furthermore, mice deficient in the S1P degrading enzyme S1P lyase have demonstrated decreased cellularity in the spleen, consistent with our results on the influence of circulating S1P on lymphocyte trafficking from the spleen.