NTR: Codeine sensitivity (Triggers or responses: drugs or treatments)

[pnrobinson]

New term request Codeine sensitivity (segal_140310214752):

[pnrobinson]

@MickeySegal

there are three term requests with X sensitivity. I am not sure this is a good pattern for HPO, because if we are talking about sensitivity to get side effects from X medication, we would need a term for every medication. I will close these three issues unless I am misunderstanding the intent?

[MickeySegal]

This is a genetic defect in metabolizing codeine: https://www.omim.org/entry/608902

[kanems]

@MickeySegal MedGen has drug sensitivity/abnormal response terms: https://www.ncbi.nlm.nih.gov/medgen/324697 (Codeine) https://www.ncbi.nlm.nih.gov/medgen/?term=Warfarin+sensitivity%2C+X-linked and https://www.ncbi.nlm.nih.gov/medgen/148193 (two Warfarin terms) https://www.ncbi.nlm.nih.gov/medgen/?term=Mercaptopurine+response

We'd love it if another group took up the charge to standardize the concepts and terminology for abnormal drug response as a clinical concept, but I think these are too broad in presentation to be distinct phenotypes in HPO. (Consider that codeine sensitivity/ ultrarapid metabolism itself can present as a constellation of symptoms: "As a result, even with therapeutic doses of codeine, these individuals may experience the symptoms of morphine overdose, which include extreme sleepiness, confusion, and shallow breathing, which in some instances can be fatal.")

[MickeySegal]

There are 2 useful UMLS terms for this finding: https://uts.nlm.nih.gov/uts/umls/concept/C0009216 https://uts.nlm.nih.gov/uts/umls/concept/C0274612

If those fit the HPO mission I'll be glad to add such as HPO term. Otherwise we'll just use the UMLS terms, which unfortunately haven't made it into MedGen, but we and MedGen periodically compare notes and suggest UMLS terms that MedGen should include.

[pnrobinson]

@kanems the HPO is planning to look at pharmacogenetic features. As you suggest, there are two ways (at least) of modelling

1. X (in)sensitivity - the clinical observation that the administration of X presents with reproducible undesired consequences (fails to achieve the desired effects at dosages that are expected to do so)
2. Reduced activity of Y - measurement of enzyme activity that usually metabolizes X

Both of these would in principle be in scope for HPO, since they are clinical observations. One occurrence "X sensitivity" is a compound phenotype but we would be referring to the tendency (Similar to recurrent otitis media).

Also pinging @mellybelly @cmungall @matentzn

[cmungall]

metabolic phenotypes such as decreased activity of X seem reasonable. Be good to align with how this is done in the model organism phenotype ontologies, I think this is the pattern: https://github.com/obophenotype/upheno/tree/master/src/patterns/dosdp-patterns#abnormally-increased-rate-of-molecular-function

[pnrobinson]

I am just not sure that the human phenotype observation is done in the same way as with models, I think that X sensitivty is also used a lot. I will try to find some relevant literature.