ga4gh / ga4gh/va-spec

Generalize the 'Case-Control' Annotation Type

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Description

The **'Case-Control' Annotation Type** we proposed a Variant Annotation category in our initial list [here](https://docs.google.com/document/d/1csUrC4kX6G1V1GIz07btQQ3oL_cdDPJShuauL_uCjEw/edit#heading=h.fo3u8tl041ts) was informed by the ClinGen CaseControl Annotation example [here](https://docs.google.com/document/d/1WbW2ts7qX3ONJNj22BlcW4KqfxcPdLsUcnlua4SSZCc/edit#heading=h.ld2eam1p6tnu). It is defined as "an annotation about the relative frequency of an allele as in affected vs unaffected study groups of a case-control clinical study"

Proposing here to generalize this variant annotation category so it is inclusive of any study comparing variant frequency between study groups (i.e. not just case-control based studies).

We should consider what other types of studies we may want/need to include here (e.g. cohort studies? studies comparing freq of a variant in ER+ breast cancer and ER- breast cancer). Then define a name that fits/covers all of these, and specify the definition and scope of what is stated in this category of annotation.

### Proposal:
- **Annotation Type**: Relative Population Allele Frequency
- **Definition**: an annotation about the relative frequency of an allele as in two defined populations or cohorts (e.g. affected vs unaffected study groups of a case-control clinical study)
- **In scope for this annotation type**: findings/data from a particular study, which may include variant frequencies calculated for each population/cohort, and optionally things like odds ratios (OR) or relative risk scores (RR) derived from these frequencies.
- **Out of scope for this annotation type:** broader conclusions/clinical interpretations about things like the risk/predisposition of carriers of the variant for some disease, or the pathogenicity of the variant. These would be higher-order annotations that might be based on one or more relative population frequency annotation used as evidence to infer such a broader conclusion. See proposal for a 'Predisposition Annotation' in issue #3

See additional notes in the revised category proposal [here](https://docs.google.com/document/d/1J4AqGDEqyK8KAzfiowgHYKJNvzHuwHSHgkN9dleLemY/edit#heading=h.lsfbnpc8zjdj).

Contributor guide

Open the contributing guide

Research direction

Review the initial and revised category proposals linked in the issue, then compare the proposed scope with issue #3's Predisposition Annotation. Done means reaching agreement on the annotation name, definition, included study findings, and excluded higher-order interpretations.

Written by the indexing model from the issue text.

Assessment

Domain
bioinformatics
Issue type
Feature
Difficulty
5/5
Estimated time
Over a week
Activity status
Stale
Clarity
Mostly clear
Newbie friendliness
25/100

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