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 |
|---|---|---|---|---|---|---|---|
| LDL cholesterol | -0.0398 | 0.0146 | 0.00648 | Wald ratio | 1 | cis | NA |
| Serum cystatin C (eGFRcys) | 0.0138 | 0.00515 | 0.00727 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: pernicious anaemia | 0.258 | 0.0967 | 0.00764 | Wald ratio | 1 | cis | NA |
| Heel bone mineral density (BMD) T-score automated | -0.0224 | 0.00869 | 0.01 | Wald ratio | 1 | cis | NA |
| Total cholesterol | -0.0369 | 0.0144 | 0.0103 | Wald ratio | 1 | cis | NA |
| Type 2 diabetes | -0.0801 | 0.0334 | 0.0165 | Wald ratio | 1 | cis | NA |
| Low grade serous ovarian cancer | 0.311 | 0.134 | 0.0201 | Wald ratio | 1 | cis | NA |
| Fractured bone site(s): Wrist | 0.101 | 0.0434 | 0.0202 | Wald ratio | 1 | cis | NA |
| Forced expiratory volume in 1-second (FEV1) | 0.0135 | 0.00581 | 0.0203 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) | -0.261 | 0.116 | 0.0246 | Wald ratio | 1 | cis | NA |
| Sodium in urine | -0.0146 | 0.00661 | 0.0271 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse | 0.165 | 0.0777 | 0.0337 | Wald ratio | 1 | cis | NA |
| …and 94 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
42 association rows across 27 traits (37 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 |
|---|---|---|---|---|---|
| Lysosomal alpha-glucosidase levels | 3e-375 | rs2304849 | 3 | GCST90248358 | no MR -> candidate analysis |
| Serum levels of protein GAA | 4e-85 | rs2304849 | 1 | GCST90090674 | no MR -> candidate analysis |
| Blood protein levels | 1e-48 | rs12450199 | 1 | GCST006585 | no MR -> candidate analysis |
| SGSH protein levels | 9e-33 | rs143436385 | 3 | GCST90470615 | no MR -> candidate analysis |
| Mean corpuscular hemoglobin concentration | 4e-28 | rs12451471 | 3 | GCST90002391 | no MR -> candidate analysis |
| Hematological traits (multi-trait analysis) | 5e-27 | rs12451471 | 1 | GCST90838671 | no MR -> candidate analysis |
| Height | 2e-24 | rs3816257 | 1 | GCST90245848 | MR: beta=0.00759, p=0.351 (cis) |
| Platelet distribution width (UKB data field 30110) | 4e-19 | rs3816257 | 1 | GCST90468097 | no MR -> candidate analysis |
| Mean corpuscular haemoglobin concentration (UKB data field 3 | 8e-19 | rs12451471 | 1 | GCST90468085 | no MR -> candidate analysis |
| High light scatter reticulocyte percentage of red cells | 2e-16 | rs149900590 | 1 | GCST90002386 | no MR -> candidate analysis |
| Plateletcrit | 1e-15 | rs3834976 | 2 | GCST90002400 | no MR -> candidate analysis |
| High light scatter reticulocyte count | 1e-15 | rs149900590 | 1 | GCST90002385 | no MR -> candidate analysis |
| …and 15 more traits (see JSON) |
Top diseases by Open Targets association (of 2642 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 |
|---|---|---|---|---|
| Glycogen storage disease due to acid maltase deficiency | 0.989 | — | established (curated) | no MR -> candidate analysis |
| glycogen storage disease II | 0.989 | — | established (curated) | no MR -> candidate analysis |
| glycogen storage disease due to acid maltase deficiency, infantile onset | 0.525 | — | established (curated) | no MR -> candidate analysis |
| glycogen storage disease due to acid maltase deficiency, late-onset | 0.821 | — | established (curated) | no MR -> candidate analysis |
| disorder of glycogen metabolism | 0.864 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of the cardiovascular system | 0.885 | — | established (curated) | no MR -> candidate analysis |
| myopathy | 0.559 | — | established (curated) | no MR -> candidate analysis |
| glycogen storage disease due to glycogen branching enzyme deficiency | 0.559 | — | established (curated) | no MR -> candidate analysis |
| Elevated circulating creatine kinase concentration | 0.547 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.559 | — | established (curated) | no MR -> candidate analysis |
| glycoprotein storage disease | 0.559 | — | established (curated) | no MR -> candidate analysis |
| glycogen storage disease due to glucose-6-phosphatase deficiency type IA | 0.547 | — | established (curated) | no MR -> candidate analysis |
| Acute rhabdomyolysis | 0.438 | — | established (curated) | no MR -> candidate analysis |
| Rare genetic deafness | 0.438 | — | established (curated) | no MR -> candidate analysis |
| Abnormality of metabolism/homeostasis | 0.438 | — | established (curated) | 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 (Lysosomal alpha-glucosidase) |
| gnomAD constraint | pLI=1.7e-25, LOEUF=1.01 — LoF-tolerant |
| GWAS Catalog | 89 unique SNPs / 178 rows |
| ClinVar | 3676 records; 22 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 2642 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 ‘GAA’ and resolved to ‘Lysosomal alpha-glucosidase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 3676 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 27 traits by best p-value, aggregated from 42 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/P10253 — 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/ENSG00000171298/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2608/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/GAA — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/GAA — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=GAA%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/GAA — GWAS Catalog search API (live; release not exposed)