Predicting effector genes for complex diseases and traits: your feedback needed!

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Researchers who perform genome-wide association studies (GWAS) often aggregate and integrate multiple other evidence types in order to predict the effector (causal) genes at GWAS loci (see some examples). We distinguish these post-GWAS lists from other candidate gene lists that are based on, for example, rare or clinically relevant variation or on sources other than genetics. There are currently no community standards for organizing or sharing lists of predicted effector genes. This survey represents a first step towards developing the standards, infrastructure and incentives required to promote and enable sharing, interoperability, and updating of these lists. We hope to gather your input to help us shape the agenda for a hybrid workshop to be held in September 2024 (see below). This survey will be open through April 30, 2024.

Which terminology do you think is most appropriate for a gene that is predicted to be responsible for a genetic association? (all descriptors would be accompanied by "predicted")

Not appropriate

Appropriate

Most appropriate

Effector gene

Causal gene

Causative gene

Mechanistic gene

Functional gene

Candidate gene

Prioritized gene

The descriptor(s) chosen above, but referring to a transcript rather than a gene

Clear selection

If you have a strong opinion about which terms are appropriate or inappropriate, please explain your reasoning. Do you have suggestions for better ways to describe these genes?

How do you use, or plan to use, lists of predicted effector genes? (select all that apply)

To confirm an independent finding

As a training or validation set for machine learning

As an input to an bioinformatic analysis or pipeline

As one line of evidence in a manual curation workflow

As a starting point for generating a hypothesis about a gene or set of genes

I don’t use or plan to use them

Other:

Which effector gene lists are you interested in?

Only my primary disease/trait of interest (e.g., diabetes)

My primary disease/trait of interest and closely related traits (e.g., diabetes, blood glucose levels, insulin sensitivity)

Any list containing my gene(s) or pathway of interest (across phenotypes)

Any well established or trusted list (trait agnostic)

Other:

Where would you go to find these lists at the moment?

The scientific literature

The Knowledge Portals (e.g., a2fkp.org)

I generate my own lists

Other:

Please rate the potential barriers to using these lists.

This is a barrier

This is not a barrier

Lack of trust in other people’s work

Lack of transparency on methods used to derive them

Lack of provenance for underlying data

Lack of standardized confidence assertion

Lack of standardized ranking system

Difficult to find lists

Lack of a single "gold-standard" list for a trait

Clear selection

Please comment on any additional barriers to your making use of these lists.

Please rate how valuable you find these types of effector gene list:

1 (most valuable)

6 (least valuable)

Bioinformatics derived - one line of evidence

Bioinformatics derived - multiple lines of evidence

Manual curation derived - one line of evidence

Manual curation derived - multiple lines of evidence

Combination of bioinformatics and manual curation, with multiple lines of evidence

Any of the above as long as I know the data provenance and methodology

Clear selection

Should predicted effector gene lists based on the genes at GWAS loci be distinguished from candidate gene lists based on rare or clinically relevant variation or on sources other than genetics?

Yes

Other:

Clear selection

Thinking about scoring and categorization, which type of list do you prefer?

Lists that place genes in different categories (such as Causal, Strong, Possible; e.g., bit.ly/4bSHFOz)

Lists that assign numerical scores to genes (e.g., bit.ly/3wJAfgj)

Lists that don’t assign a score or category, but do provide supporting evidence (e.g., bit.ly/4abNUvp)

No preference

Thinking about the range of genes presented in a list, which type of list do you prefer?

Lists that include evidence for all genes within a certain distance of a GWAS locus (e.g., bit.ly/3TeVX4P)

Lists that include evidence for only the single most likely causal gene at each GWAS locus (e.g., bit.ly/3T0Q75A)

Would it be valuable to have the ability to compare multiple lists?

Yes, for the same trait

Yes, across traits

Would you like to be able to interact with these lists, assigning different weights to different evidence types according to your judgement of the value of each evidence type?

Yes

Clear selection

Any other comments or suggestions?

Please tell us which of these categories apply to you.

Data generator (effector gene lists)

Data generator (GWAS data)

Methods developer for effector gene lists

Methods developer for GWAS

Effector gene list user

Resource provider

Funder

Journal editor

Interested primarily in human common/complex trait genetics

Interested primarily in other field (not human common/complex trait genetics)

Member of an academic or nonprofit institution

Member of industry

Other:

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