PEG Evidence Categories

🌟 Why do we need PEG evidence categories?

Predicted Effector Gene (PEG) lists are built from diverse sources of evidence, ranging from genetic associations and computational predictions to functional assays and literature curation. Each source has its own origin, methodology, and level of confidence.

To ensure clarity and interoperability, we group these diverse evidence types into standardised categories that are widely recognised in causal gene exploration. This provides a shared framework for describing variant–gene, variant–phenotype, and gene–phenotype relationships within a given phenotype, in a way that is easy to explore and compare.

➡️ Organising evidence into categories helps users:

• Interpret consistently – understand the general type of support behind each gene.
• Compare across studies – align evidence types, even when detailed sources differ.
• Build trust and transparency – see at a glance how predictions were made.

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PEG Evidence Categories

🔀 Variant-centric 🔀

Evidence categories	Abbreviation	Explanation
Linkage disequilibrium	LD	Variant is highly correlated with another variant and may act as a proxy.
Finemapping and credible sets	FM	Finemapping results, or variant is in a credible set with high posterior probability of being causal.
Colocalisation	COLOC	Variant affects multiple traits (e.g. a complex trait and gene expression data) at the same locus.
Molecular QTL	QTL	eQTL, sQTL, pQTL. Variant affects gene expression or splicing or protein level.
Mendelian Randomization (MR)	MR	Uses genetic variants as proxies for exposures to test their causal effect on outcomes.
Regulatory region	REG	Variant lies in open chromatin or enhancer/promoter elements in relevant tissue.
Chromatin interaction	3D	Variant physically contacts gene promoter via 3D structure.
Predicted functional impact	FUNC	Variant predicted to disrupt gene/protein function or regulatory motifs.
Proximity to gene (distance)	PROX	Variant is located within or near gene boundaries.
Genome-wide association (GWAS) signal	GWAS	P-value from source GWAS for association of variant with trait specified in metadata file.
PheWAS (Phenome-Wide Association Study)	PHEWAS	Variant is associated with multiple traits — may reveal pleiotropic effects.

🧬 Gene-centric 🧬

Evidence categories	Abbreviation	Explanation
Protein–protein interaction	PPI	Gene’s protein interacts with other disease-relevant proteins.
Pathway or gene sets	SET	Gene is part of a known pathway or complex relevant to the phenotype.
Gene-based association	GENEBASE	Gene-based analysis of association of variants (common or rare) in gene with trait.
Expression	EXP	Gene is differentially expressed in relevant tissue or patients. e.g. the gene is highly expressed in phenotype-related tissues than others
Perturbation	PERTURB	Gene perturbation causes phenotype-relevant effects in lab or model organisms (knock out animal/cell line, human organoid).
Biological Knowledge Inference	KNOW	Gene–phenotype relationships can be inferred based on known biology, even when there is no direct genetic or experimental evidence linking the specific gene or variant to the new phenotype. No references are provided.
Genetically predicted trait association (TWAS/PWAS)	TPWAS	Gene’s genetically predicted expression or protein level is associated with phenotype. Transcriptome- or proteome-wide assocation studies
Drug related	DRUG	Gene is targeted by drugs known to treat or influence phenotype.

Variant or Gene centric evidence

Evidence categories	Abbreviation	Explanation
Cross-phenotype	CROSSP	Gene or variant already established in a related phenotype (biologically similar).
Literature curation	LIT	Human-curated gene or variant–disease links from literature.
Association from curated database	DB	Variant or Gene is curated as causal or related to the phenotype from existing database, like ClinVar, ClinGen, OMIM, etc.