Micronutrient genetics

Discussion document to possibly start a global initiative to structure the knowledge base for genetic variations related to micronutrients.

Sent to Jim Kaput (NCTR), John Mathers (NuGO), Richard Cotton (Variome), Giuditta Perozzi (Genes&Nutrition), Jose Ordovas (Tufts)

9 May 2008

  1. micronutriënt efficacy depends on a series of processes, each of them with a number of related genes. These are (a.o.)
  2. absorption
  3. transport
  4. biotransformation
  5. excretion
  6. binding and storage
  7. cellular mechanism of action.
  1. For most of the micronutrients, a number of obvious gene variants / polymorphisms are studied and taken into account in risk/benefit (= dietary recomendation) studies. In most cases, even for the obvious polymorphisms, this is a difficult task. Evidence is derived from epidemiology, prospective cohorts and intervention studies. Also, toxicology works on genetic evaluations (copper example with Carl Keen involved).
  1. I don`t really know if there are clinically relevant (rare) genetic diseases related to micronutrients. Yet, a quick pubmed search shows that this is the case, for example iron, copper, again copper. So, from both ends of the spectra (clinical practice and nutrition research, the genetics of micronutrients is relevant
  1. Does HuGENet provide a solution with its toolbox? Once they have adapted to SNP level (now they work on gene level) and have included environmental terms in their search engine, they would be able to provide all published information. Jose, Jim and Ben will connect with them. Jim, Giuditta and Dick might discuss this with Muin Khouri at the Variome meeting.
  1. To my knowledge, no systematic effort is made to make an inventory (from a micronutrient point of view) to database and access all relevant genetic data and genotype – phenotype information. So, do we need to systematically tackle this issue, on top of the many fragmented research efforts? Is this timely? Already done? Are we the right group? Can we kick off right away? Or should we first do a SWOT?
  1. If yes, then we should organize this: decide on which micronutrient, which priority, how to publish, how to meet, how to store, how to query, who should do this, how should we meet, etc. In other words: what is the mechanism of getting this done. Let`s have a step by step look at this, based on the discussions in Melbourne and thoughts during jogging.
  1. Establish a list of all (relevant) micronutrients. Do we simply do all? Do we rank them? On what basis?
  1. A working group per micronutrient, headed by a leader.
  1. A review for each micronutrient, which describes (in a pre-formatted and structured way) all issues that link genes with
  1. A journal that adopts this effort. First option is to adopt Genes and Nutrition for this purpose. This is the easy way, but we need to put effort in rapidly increasing its impact. Disadvantage is that it is neither open access nor money generating for a society (see later). Alternatively, we could create a new nutrigenomics journal but I do not volunteer!
  1. A structure to capture the results. On the gene level, this is provided by the variome project / NCBI, but well need to make a micronutrient oriented query system = database. This could be structured according to the pipeline: micronutrient à related processes à related genes (= embedding in the variome / NCBI DB). I already have a wiki in place for all micronutrient, as part of the Eurreca / NuGO activities (see http://www.eurreca.org/everyone/1431). This can easily be modified to capture genetic info according to the above pipeline. I`ve made a simple example at http://www.nugowiki.org/index.php/Riboflavin#Genetic_variations. The password protection willsoon be removed from this wiki. I am not convinced that this wiki is the solution, but it just triggers thoughts.
  1. A series of meetings to launch this properly, culminating in a big meeting where all teams meet. I suggest to do this properly and begin at the end: Let`s nominate NuGOweek September 2009 as the big meeting. We might rename it nutrigenomics week, and we could organize the micronutrient genetics back-to-back to the other parts of NuGOweek.
  1. A society that covers this and glues the efforts. We have spent a lot of time and thinking on the nutrigenomics society. Is it time to really establish this? We`ve done most of the thinking, the website is ready.
  1. Money. NuGO can pay workshop costs. I run workpackage “vulnerability” in another EU project Eurreca (www.eurreca.org). I`m checking how I can include this. It would fit.