MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Neuroticism | -0.0718 | 0.016 | 6.80e-06 | Wald ratio | 1 | cis | NA |
| Weight | 0.0332 | 0.0105 | 0.00154 | Wald ratio | 1 | cis | NA |
| Parkinson’s disease | 0.652 | 0.209 | 0.00184 | Wald ratio | 1 | cis | NA |
| Lung adenocarcinoma | 0.436 | 0.148 | 0.00315 | Wald ratio | 1 | cis | NA |
| Lung cancer | 0.254 | 0.0934 | 0.0065 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities | 0.175 | 0.07 | 0.0127 | Wald ratio | 1 | cis | NA |
| HbA1C | -0.0387 | 0.0164 | 0.018 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: gout | 0.186 | 0.0833 | 0.0256 | Wald ratio | 1 | cis | NA |
| Primary sclerosing cholangitis | -0.336 | 0.152 | 0.0265 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting | 0.306 | 0.143 | 0.0321 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis | 0.278 | 0.135 | 0.0393 | Wald ratio | 1 | cis | NA |
| Triglycerides | -0.0455 | 0.0223 | 0.0418 | Wald ratio | 1 | cis | NA |
| …and 96 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
121 association rows across 51 traits (99 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait | best p | lead SNP | n assoc | study | MR status |
|---|---|---|---|---|---|
| Parkinson’s disease | 4e-170 | rs356182 | 39 | GCST90308590 | MR: beta=0.652, p=0.00184 (cis) |
| Parkinson’s disease or first degree relation to individual w | 4e-154 | rs356182 | 4 | GCST009325 | no MR -> candidate analysis |
| Serum levels of protein SNCA | 2e-47 | rs2245801 | 2 | GCST90090202 | no MR -> candidate analysis |
| Parkinson disease (MTAG) | 6e-41 | rs356219 | 2 | GCST90256604 | no MR -> candidate analysis |
| Blood protein levels | 8e-30 | rs1372518 | 2 | GCST006585 | no MR -> candidate analysis |
| Lewy body dementia (MTAG) | 3e-26 | rs1372518 | 1 | GCST90133379 | no MR -> candidate analysis |
| Insomnia | 2e-19 | rs356179 | 15 | GCST90131901 | no MR -> candidate analysis |
| Dementia with Lewy bodies | 3e-17 | rs7680557 | 4 | GCST90001390 | no MR -> candidate analysis |
| Alpha-synuclein levels (SNCA.8458.111.3) | 1e-16 | rs2245801 | 1 | GCST90240258 | no MR -> candidate analysis |
| REM sleep behavior disorder (probable or isolated) | 3e-16 | rs3756059 | 1 | GCST90244078 | no MR -> candidate analysis |
| REM sleep behavior disorder in Parkinson’s disease | 2e-15 | rs10005233 | 2 | GCST90269977 | no MR -> candidate analysis |
| Drinks per week | 2e-14 | rs2619364 | 1 | GCST90243989 | no MR -> candidate analysis |
| …and 39 more traits (see JSON) |
Top diseases by Open Targets association (of 801 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 |
|---|---|---|---|---|
| Hereditary late-onset Parkinson disease | 0.859 | — | established (curated) | no MR -> candidate analysis |
| Young adult-onset Parkinsonism | 0.878 | — | established (curated) | no MR -> candidate analysis |
| Lewy body dementia | 0.816 | — | established (curated) | no MR -> candidate analysis |
| Parkinson disease | 0.856 | — | established (curated) | no MR -> candidate analysis |
| insomnia | 0.63 | — | common-variant locus | no MR -> candidate analysis |
| REM sleep behavior disorder | 0.61 | — | common-variant locus | no MR -> candidate analysis |
| parkinsonian-pyramidal syndrome | 0.608 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of the skeletal system | 0.552 | — | common-variant locus | no MR -> candidate analysis |
| Anxiety | 0.517 | — | common-variant locus | no MR -> candidate analysis |
| Cachexia | 0.512 | — | common-variant locus | no MR -> candidate analysis |
| benign chondrogenic neoplasm | 0.484 | — | common-variant locus | no MR -> candidate analysis |
| schizophrenia | 0.458 | — | common-variant locus | no MR -> candidate analysis |
| disease of genitourinary system | 0.456 | — | common-variant locus | no MR -> candidate analysis |
| vitiligo | 0.427 | — | common-variant locus | no MR -> candidate analysis |
| neurotic disorder | 0.412 | — | common-variant locus | no MR -> candidate analysis |
Of the 15 rows above, 15 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | 2 known modulators (Alpha-synuclein) |
| gnomAD constraint | pLI=0.48, LOEUF=0.715 — LoF-tolerant |
| GWAS Catalog | 93 unique SNPs / 151 rows |
| ClinVar | 206 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 801 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘SNCA’ and resolved to ‘Alpha-synuclein’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 206 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 51 traits by best p-value, aggregated from 121 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/P37840 — 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 v3.0phenome: https://platform.opentargets.org/target/ENSG00000145335/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL6152/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SNCA — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SNCA — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SNCA%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SNCA — GWAS Catalog search API (live; release not exposed)