STSM: GWAS 2.0: alternative approaches to association studies and indepth follow-up on detected signals

I am a postdoctoral researcher at PTP Science Park (Lodi, Italy), and my focus is mainly on the study of signatures of selection and of genotype-phenotype signals of association in animal populations, especially livestock. With support of the COST ACTION “METHAGENE”, I had the opportunity to spend a period of 18 days at the University of Cardiff under the supervision of dr. Pablo Orozco-ter Wegel.
The aim of my STSM was to develop a method to follow up on detected signals of association for traits related to milk production and environmental impact in dairy cattle. SNP genotypes, milk yield, methane emissions and feed intake of individual cows were available. From standard GWAS and alternative approaches (resampled predictive models, ROH-analysis) SNP significantly associated with the traits of interest were detected, then tracked on the genome, and the related genes were further investigated using Gene Ontology and pathway analysis.
First, we prototyped R pipelines to query relevant biological databases. We used different databases: KEGG (http://www.genome.jp/kegg/), Reactome (http://www.reactome.org) and GOrilla (http://cbl-gorilla.cs.technion.ac.il). This step helped identify the most suited database.
We preferred KEGG, since it is free, widely used by the scientific community, and its cattle annotation appeared to be relatively more complete.
In the second week we interpreted the results obtained from the GO analysis and enrichment pathway analysis. The scripts written during the STSM allowed us to retrieve: i) the GO terms associated with genes supposed of being involved in milk production, feed intake and methane emissions in dairy cattle: cellular components, biological processes, molecular functions; ii) the most likely associated metabolic pathways.
The first two pathways are involved in the production of purines (two genes, ALLC and PDE7A) and in lipid metabolism (one gene, DGAT1).
However, these results are preliminary: the understanding of the involved pathways is complex and not yet complete.
The work at the University of Cardiff with Dr. Pablo Orozco-ter Wengel gave me a chance to interact with a very experienced and talented research group. The next few months will be critical to further process the results, and will be the basis of a scientific pubblication in collaboration with Dr. Orozco-ter Wengel’s group.