Nutrigenomics - a source of new statistical challenges
by Christopher M Triggs and Lynnette R Ferguson
Abstract: Nutrigenomics New Zealand was established to develop a capability that could be applied to the development of gene-specific personalised foods. The programme includes two Crown Research Institutes (Plant and Food Research and AgResearch) and the University of Auckland, involving 55 named scientists spread across several different New Zealand centres. Inflammatory Bowel Diseases, in particular Crohn's disease, are being used as proof of principle. There is known genetic susceptibility to Crohn's disease, which is impacted by environment and diet. We have established case-control studies of more than 1,000 IBD patients compared with approximately 600 unaffected controls, and are studying these for single nucleotide polymorphisms (SNPs) and gene copy number variants that associate with disease. At the same time, we are seeking dietary information, especially in terms of food tolerances and intolerances. By these means, we have identified mushroom intolerance in individuals carrying variants in an organic cation transporter gene (OCTN1). These human disease SNPs is incorporated into design paired reporter gene constructs, that is otherwise identical cell lines, with and without the variant SNP of interest. These cell lines are then tested in a high throughput screen to determine the phenotypic effects of nutrients, bioactive compounds, and food extracts. The most effective compounds are then tested in mouse models, where the endpoints are transcriptomics, proteomics and metabolomics, as well as direct observation of pathologic changes in the diseased gut. The programme relies on high quality data management, and has lead to a range of problems in bioinformatics and biostatistics.
Acknowledgements: Nutrigenomics New Zealand (www.nutrigenomics.org,nz) is a collaboration between AgResearch, Plant & Food Research, and the University of Auckland and is largely funded by the New Zealand Foundation for Research, Science and Technology.
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