CausalSentinel

Protein Dossier — WISP1 (CCN family member 4)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome	beta	se	p	method	nSNP	cis/trans	coloc
Rheumatoid arthritis	-0.142	0.0374	1.46e-04	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	-0.0754	0.0255	0.00304	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis	-0.172	0.0737	0.0194	Wald ratio	1	cis	NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis)	-0.0655	0.0288	0.0227	Wald ratio	1	cis	NA
Forced vital capacity (FVC)	-0.00898	0.00435	0.039	Wald ratio	1	cis	NA
Hearing difficulty or problems: Yes	0.0179	0.009	0.0463	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: osteoporosis	-0.0915	0.0468	0.0505	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: pernicious anaemia	0.161	0.0839	0.0542	Wald ratio	1	cis	NA
Serum cystatin C (eGFRcys)	-0.00821	0.0043	0.0563	Wald ratio	1	cis	NA
Forced expiratory volume in 1-second (FEV1)	-0.00838	0.00459	0.0679	Wald ratio	1	cis	NA
Urate	0.0235	0.0131	0.0733	Wald ratio	1	cis	NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation	0.0619	0.0348	0.0752	Wald ratio	1	cis	NA
…and 97 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

Dataset	Trait	Author	Year
prot-c-3057_55_1	WISP-1	Suhre K	2019

3. GWAS Catalog results — traits with signal at this locus

No GWAS Catalog associations mapped to this gene.

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 488 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease	genetic assoc.	burden (ExWAS)	causal status	MR status
hypothyroidism	0.769	—	common-variant locus	MR: beta=-0.0754, p=0.00304 (cis)
Graves disease	0.738	—	common-variant locus	no MR -> candidate analysis
rheumatoid arthritis	0.656	—	common-variant locus	MR: beta=-0.142, p=1.46e-04 (cis)
myxedema	0.656	—	common-variant locus	no MR -> candidate analysis
thyrotoxicosis	0.591	—	common-variant locus	MR: beta=-0.172, p=0.0194 (cis)
autoimmune disease	0.525	—	common-variant locus	no MR -> candidate analysis
hyperthyroidism	0.525	—	common-variant locus	MR: beta=-0.172, p=0.0194 (cis)
respiratory system disorder	0.509	—	common-variant locus	no MR -> candidate analysis
hypotensive disorder	0.482	—	common-variant locus	no MR -> candidate analysis
ovarian neoplasm	0.293	—	common-variant locus	no MR -> candidate analysis
Back pain	0.23	—	common-variant locus	no MR -> candidate analysis

Of the 11 rows above, 7 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer	Result
ChEMBL druggability	not available — no ChEMBL target (undrugged)
gnomAD constraint	not available
GWAS Catalog	no mapped SNPs
ClinVar	no records
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 488 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘WISP1’.
• gnomad — No gnomAD constraint data.
• gwas — No GWAS Catalog SNPs mapped to this gene.
• clinvar — No ClinVar records.
• pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).
• gwas_traits — No GWAS Catalog associations mapped to this gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/O95388 — UniProt release 2026_02 (10-June-2026)
• mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000104415/associations — Open Targets data release 26.06

Provenance

• Generated: 2026-08-14T05:38:15 · Tier: A
• Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
• MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
• Tool errors this run: none

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