New term request for Kanoni PMID 34025683

[earlEBI]

For new term requests, please provide the following information:

Preferred term label

Nutritional supplement exposure measurement

Textual definition

Quantification of some aspect of the consumption of dietary nutritional supplements.

Suggested parent term

environmental exposure measurement

more info from paper

"Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects."

[kallia-p]

@earlEBI @ljwh2 @dosumis After looking at the PMID (Table 3) I think that there are associations with several traits in response to mastiha supplementation. Therefore I was thinking if you'd like to create a 'response to mastiha supplement exposure' term and co-annotate this with each trait shown as the outcome in Table 3 of this paper. I have created a spreadsheet with my suggestions for co-annotation based on the variant-trait associations and variant-gene expression associations taken from the fields 'outcome' and 'variant' in Table 3. Interestingly I also noticed that in EFO we do not have terms for specific gene expression level measurements, I will add it to the agenda to review this in our next meeting. https://docs.google.com/spreadsheets/d/1cinCaYTLO0gaZ0ll3RRpPqED04tF_W3je6al3eGs0og/edit#gid=0

[earlEBI]

hi @kallia-p thank you for this. The specifics of the associations should be covered by the reported trait/"disease trait", as you can see from this screenshot:

I think the 'Nutritional supplement exposure measurement' would still be a useful EFO term to have and would cover this case, unless you are keen to create the specific mastiha term as well. I will open tickets for some gene expression terms, that would be great, thank you.

[kallia-p]

@earlEBI Thanks for the table. I guess there are three questions here. 1/ Are we treating this as a response to term or as a gene-environment interaction? I thought response to term because the outcomes are measured as part of a clinical trial following supplementation with mastiha and compared to a placebo group. For example see annotation of https://www.ebi.ac.uk/gwas/efotraits/EFO_0009308. If yes then in EFO we have a parent term 'response to diet'. If no then we can create the term as an exposure measurement. 2/ Do we create a specific vs non specific term for mastiha? I believe specific will be in line with other nutritional measurement terms that we have under either 'response to diet' (e.g. response to vitamin supplement) or 'environmental exposure measurement' (e.g. vitamin and fish oil supplement). Nutritional supplement exposure measurement could be created as a parent term for mastiha supplement exposure measurement and I could move terms like vitamin and fish oil supplement under this parent to differentiate from other types of exposure. 3/ With regards to gene expression terms I sent this query to the team over Slack and intend to discuss at the EFO-GWAS meeting this Thursday. "Is there a reason that we haven't been annotating gene expression measurements separately from protein level measurements in GWAS catalog EFO trait. For example we have some GWAS associations with IL-6 levels (measured at the protein level) and IL-6 gene expression. The existing EFO term 'interleukin-6 measurement' is defined as "a quantification of interleukin-6, a pro-inflammatory and anti-inflammatory cytokine" and from the tree level view one would think it's the protein that's been measured. Should we be making a distinction by creating a new term IL-6 gene expression measurement or not?"

Please let me know what are your thoughts on these points.

[ljwh2]

RE 1/ there are some differences in the model between the older example and the current paper. in the old example they measure change in biomarker levels (triglycerides) in response to a supplement, all individuals are supplement-treated and they perform a straight GWAS of responders vs non responders, hence it’s appropriate to annotate with a response term. In the current paper, they measure change in biomarkers after 6 months of treatment with mastiha or placebo. Here they use a GxE model with mastiha as the environmental exposure, so it’s appropriate to annotate with an exposure measurement. I see the argument for annotating both with response terms (from the user perspective) and this is something we could include in the bigger discussion about response terms, but I think the terms requested are correct for now. 2/ agree with your proposal

[kallia-p]

@ljwh2 @earlEBI Thank you Liz and Laura it makes sense. I guess this just leaves the discussion to be had about gene expression measurement traits.

[kallia-p]

@earlEBI Added the new terms. This also adresses #1342

EFO subject_ID_label | EFO subject_ID | EFO parent subject_ID_label | EFO subject_ID -- | -- | -- | --   |   |   |   mastiha supplement exposure measurement | EFO_0600067 | nutritional supplement exposure measurement | EFO_0600066 blood glutathione peroxidase measurement | EFO_0600071 |   |   interleukin-6 gene expression measurement | EFO_0600070 | gene expression measurement | EFO_0600068 tumor necrosis factor alpha gene expression measurement | EFO_0600069 | gene expression measurement | EFO_0600068

[earlEBI]

thank you!