Sunday, November 15, 2015

CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation

Apparently, Crohn's disease and plasma palmitoleric acid have an association. Using a new technology, CPAG or Cross-Phenotype Analysis of GWAS, scientists were able to perform meta-analyses of genome-wide association studies (GWAS) and search for similarities between over 600 traits. Using GWAS is particularly helpful being that Crohn's disease is associated with a genetic variant. Pleiotropic SNPs (single polynucleotide polymorphisms) are common within the human genome, which means one genetic locus affects multiple phenotypes. The significance of cross-phenotype associations lies in the fact that they may represent pleiotropy, and it has been discovered that the PTPN22 gene is associated with many conditions, such as Crohn's disease, rheumatoid arthritis, type 1 diabetes, and more. It was found that 7% of SNPs are associated with more than one raw trait. In addition, by identifying traits associated with particular genetic variants and clustering the traits in order to visualize associations, clusters of known cholesterol-related traits, such as type 2 diabetes, obesity, and autoimmunity, were easy to see and represented known relationships. 

The results were compared using a Chao-Sorensen model, the first use of a model usually used for ecology research, to study genetics. The model assessed heterogeneity, or the discordance of observed disease groups with already defined disease group. Many traits were had a high correspondence, which can be explained by reasons such as a similar risk factor, consequence of a disease, a similar gene affecting different pathways. Crohn's disease and psoriasis only overlap with two SNPs but were found to have genes in the interleukin (IL)-23 pathway, suggesting that the risk of both conditions could be related to signaling. Researchers went on to test whether increased plasma fatty acid would induce intestinal inflammation in zebrafish to find that plasma fatty acids have an effect on intestinal inflammation. It is known that countries with high fat diets have a stronger correlation with Crohn's disease. Three different fatty acids were injected into zebrafish larvae. Palmitic acid induced a greater increase in inflammation compared to TNBS-exposed and BSA-injected. Linoileic acid was suggestive of having an anti-inflammatory effect. 
I found this study to be of great interest, as it supports that environment can have a direct effect on the expression of certain diseases. The consumption of too much unnecessary fat could lead to the expression of Crohn's disease. 

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