Open Targets therapeutic area: Congenital, familial and genetic disorders

[paolaroncaglia]

Proposed TA name: Congenital, familial and genetic disorders
Current EFO TA name: 3 Terms exist: Congenital abnormality, Genetic disorder, Inherited genetic disease (IS NOT A TA AT THE MOMENT)
Priority for OT: High
Justification: Understanding whether a disease is caused by genes (and) or the environment is of crucial important in the assessment of drug safety. Therefore, a new TA should be created to incorporate congenital, familial and genetic disorders.
Related issue: Issue 463

Congenital = existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation. https://www.thefreedictionary.com/Congential
Familial = occurring in or affecting members of a family more than would be expected by chance. https://www.thefreedictionary.com/familial
genetic = a. Of or relating to genetics or genes. b. Affecting or determined by genes https://www.thefreedictionary.com/genetic

Currently in EFO - Familial disease only exists as a specific type of disease in EFO
[OLS views of:
congenital
genetic disorder
familial cardiomyopathy]

[paolaroncaglia]

• Take into account discussion in Merge/Group Genetic diseases #463

[paolaroncaglia]

(TA = therapeutic area)

Comments on the request to have:
“Proposed TA name: Congenital, familial and genetic disorders
Current EFO TA name: 3 Terms exist: Congenital abnormality, Genetic disorder, Inherited genetic disease”

In #463 we agreed that
EFO:0000508 ‘genetic disorder’ (is already a TA)
And
MONDO:0003847 ‘inherited genetic disease’
Are the same.
So they can be merged and keep/have TA status.

NOTE FOR SELF (update 20/8/2019) need to check with Zoe:
MONDO_0003847 'inherited genetic disease' is indeed listed among obsoleted classes in the release notes for 3.9.0 (section 3 in https://github.com/EBISPOT/efo/blob/master/ExFactor%20Ontology%20release%20notes.txt), so it seems that the merge went ahead already, double-check that this was intentional, and if we need to communicate it to MONDO and if there may be any issues next time they release.

EFO MONDO:0000839 congenital abnormality
Is not currently a TA; we can certainly make it a TA if desired.

As for ‘familial’ disorders:
They may be genetic but also environmental, so we wouldn’t want to create a generic grouping term, but rather make sure that any disease that contains ‘familial’ in its label is correctly placed or axiomatised (*) as being a descendant of genetic disorder/inherited genetic disease if (and only if) that evidence is known based on its definition. Note that MONDO also doesn’t have a generic grouping term for familial disorders.

If a TA is desired to group “Congenital, familial and genetic disorders” together, we could probably create it as a parent of genetic disorder/inherited genetic disease and congenital abnormality. We should then assign TA status to the grouping superclass and remove it from genetic disorder.

(*) Note for self: e.g.
familial hyperlipidemia
Equivalent to:
hyperlipidemia (disease) and has modifier some inherited

[zoependlington]

Proposed plan:

• EFO:NEW1 'congenital, familial or genetic disorders'

  • Subclass of: Disease
  • Definition: TBC

• EFO:EDIT genetic disorder (EFO:0000508)

  • add to mapping file mapping to inherited genetic disease (MONDO_0003847)
  • make child of new EFO:NEW1

• EFO:EDIT congenital abnormality (MONDO_0000839)

  • Option 1 Create new EFO term "congenital disease" that is a child of EFO:NEW1 and map to congenital abnormality (MONDO_0000839)
  • Option 2 Add to subclass declaration TSV template as a child of EFO:NEW1

• EFO:NEW2 familial disorder

  • Subclass of: EFO:NEW1
  • Definition: TBC
  • disease and has_modifier familial (?)
    • Add "familial" disease characteristic and apply to all familial terms in EFO - terms should now classify under EFO:NEW2

[paolaroncaglia]

Note for self: may need to address the issue of how to classify diseases that have a genetic basis, but are due to de novo mutations, i.e. not present in the parents; mutations that may be present at birth (congenital), as opposed to occurring later in life (i.e. in cancers). See e.g. Menke-Hennekam syndrome 1 and 2 (OMIM entries). Also, check large chromosomal anomalies like Down syndrome, where parents surely do not have the same mutation.

[paolaroncaglia]

Note for self: there may be some useful discussion on nomenclature here monarch-initiative/mondo#1175