Pathway

Pathway-based stratification of instruments

Trait

 

P-value threshold: 1e-10
   

 

 

 Summary

This is a pilot view to explore the potential of pathway data to inform us about groups of SNPs that may share pleiotropic relationships. For a trait we identify all SNPs that can be mapped to genes/proteins, and from those genes/proteins we look for common pathways.

Data sources

  • Gene/protein to pathway mappings from Reactome
  • MR estimates from MR-EvE (Hemani et al, Automating Mendelian randomization through machine learning to construct a putative causal map of the human phenome, bioRxiv 10.1101/173682)
  • SNP-trait assocaitions are from the IEU GWAS database

 How to use

Enter the trait you are interested in, the p-value threshold you want to use, then press "Search". You can adjust the slider and press Search again to update the results.

View the top results in the Network plot tab, access and search the full results in the Table tab, or use the Query tab to find out how to download data using the API.

 Examples

 Displays the top 150 relationships

 

gwas.id gwas.trait mre_study_snp.beta mre_study_snp.se mre_study_snp.eaf mre_study_snp.pval mre_study_snp.samplesize snp.name gene.name protein.uniprot_id pathway.reactome_id pathway.name
UKB-a:248 Body mass index (BMI) -0.040227 0.003062 0.189726 2.037980e-39 336107.0 rs6265 BDNF P23560 R-HSA-9022702 MECP2 regulates transcription of neuronal ligands
UKB-a:248 Body mass index (BMI) 0.029152 0.002417 0.552780 1.683449e-33 336107.0 rs4402589 TMEM219 Q86XT9 R-HSA-6803211 TP53 Regulates Transcription of Death Receptor...
UKB-a:248 Body mass index (BMI) 0.025998 0.002545 0.335903 1.716722e-24 336107.0 rs34045288 LRFN2 Q9ULH4 R-HSA-8849932 Synaptic adhesion-like molecules
UKB-a:248 Body mass index (BMI) 0.067508 0.007598 0.025799 6.447628e-19 336107.0 rs17024393 GNAT2 P19087 R-HSA-4086398 Ca2+ pathway
UKB-a:248 Body mass index (BMI) 0.067508 0.007598 0.025799 6.447628e-19 336107.0 rs17024393 GNAT2 P19087 R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-...
UKB-a:248 Body mass index (BMI) 0.067508 0.007598 0.025799 6.447628e-19 336107.0 rs17024393 GNAI3 P08754 R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-...
UKB-a:248 Body mass index (BMI) 0.020815 0.002419 0.514078 7.737488e-18 336107.0 rs7141420 NRXN3 Q9Y4C0 R-HSA-6794361 Neurexins and neuroligins
UKB-a:248 Body mass index (BMI) 0.020815 0.002419 0.514078 7.737488e-18 336107.0 rs7141420 NRXN3 Q9HDB5 R-HSA-6794361 Neurexins and neuroligins
UKB-a:248 Body mass index (BMI) -0.020641 0.002496 0.639151 1.348652e-16 336107.0 rs2234458 EFEMP2 O95967 R-HSA-2129379 Molecules associated with elastic fibres
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-5689896 Ovarian tumor domain proteases
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK e...
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-918233 TRAF3-dependent IRF activation pathway
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-5602571 TRAF3 deficiency - HSE
UKB-a:248 Body mass index (BMI) -0.020791 0.002545 0.666379 3.082478e-16 336107.0 rs3803286 TRAF3 Q13114 R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
UKB-a:248 Body mass index (BMI) -0.022319 0.002876 0.225890 8.556576e-15 336107.0 rs2056477 MAD1L1 Q9Y6D9 R-HSA-141444 Amplification of signal from unattached kine...
UKB-a:248 Body mass index (BMI) -0.018926 0.002441 0.426708 9.048988e-15 336107.0 rs39330 RELN P78509 R-HSA-8866376 Reelin signalling pathway
UKB-a:248 Body mass index (BMI) -0.031825 0.004168 0.096761 2.249573e-14 336107.0 rs12140153 INADL Q8NI35 R-HSA-420029 Tight junction interactions
UKB-a:248 Body mass index (BMI) -0.018313 0.002405 0.497341 2.674853e-14 336107.0 rs1788808 NPC1 O15118 R-HSA-8964038 LDL clearance
UKB-a:248 Body mass index (BMI) -0.019791 0.002711 0.268192 2.907368e-13 336107.0 rs11856579 LINGO1 Q96FE5 R-HSA-193634 Axonal growth inhibition (RHOA activation)
UKB-a:248 Body mass index (BMI) 0.019463 0.002687 0.276291 4.352111e-13 336107.0 rs73169730 SLC2A2 P11168 R-HSA-210745 Regulation of gene expression in beta cells
UKB-a:248 Body mass index (BMI) -0.017698 0.002448 0.408667 4.825030e-13 336107.0 rs2292238 ERBB3 P21860 R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling
UKB-a:248 Body mass index (BMI) -0.017698 0.002448 0.408667 4.825030e-13 336107.0 rs2292238 ERBB3 P21860 R-HSA-1227986 Signaling by ERBB2
UKB-a:248 Body mass index (BMI) 0.018051 0.002564 0.673439 1.924421e-12 336107.0 rs1286138 RPS6KA5 O75582 R-HSA-437239 Recycling pathway of L1
UKB-a:248 Body mass index (BMI) 0.018051 0.002564 0.673439 1.924421e-12 336107.0 rs1286138 RPS6KA5 O75582 R-HSA-198753 ERK/MAPK targets
UKB-a:248 Body mass index (BMI) 0.018051 0.002564 0.673439 1.924421e-12 336107.0 rs1286138 RPS6KA5 O75582 R-HSA-375165 NCAM signaling for neurite out-growth
UKB-a:248 Body mass index (BMI) 0.023977 0.003406 0.146486 1.929301e-12 336107.0 rs9688977 OPRM1 P35372 R-HSA-375276 Peptide ligand-binding receptors
UKB-a:248 Body mass index (BMI) 0.023977 0.003406 0.146486 1.929301e-12 336107.0 rs9688977 OPRM1 P35372 R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
UKB-a:248 Body mass index (BMI) 0.023977 0.003406 0.146486 1.929301e-12 336107.0 rs9688977 OPRM1 P35372 R-HSA-111885 Opioid Signalling
UKB-a:248 Body mass index (BMI) 0.023977 0.003406 0.146486 1.929301e-12 336107.0 rs9688977 OPRM1 P35372 R-HSA-9022699 MECP2 regulates neuronal receptors and channels
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-198693 AKT phosphorylates targets in the nucleus
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegene...
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-1181150 Signaling by NODAL
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
UKB-a:248 Body mass index (BMI) 0.017295 0.002485 0.628085 3.399382e-12 336107.0 rs2253310 FOXO3 O43524 R-HSA-5687128 MAPK6/MAPK4 signaling
UKB-a:248 Body mass index (BMI) -0.017441 0.002519 0.348993 4.427922e-12 336107.0 rs5995843 TNRC6B Q9UPQ9 R-HSA-426496 Post-transcriptional silencing by small RNAs
UKB-a:248 Body mass index (BMI) 0.031354 0.004582 0.076028 7.744618e-12 336107.0 rs362307 HTT P42858 R-HSA-9022692 Regulation of MECP2 expression and activity
UKB-a:248 Body mass index (BMI) -0.016471 0.002430 0.427488 1.218990e-11 336107.0 rs3802858 CADM1 Q9BY67 R-HSA-420597 Nectin/Necl trans heterodimerization
UKB-a:248 Body mass index (BMI) 0.016524 0.002446 0.593047 1.421347e-11 336107.0 rs4757144 ARNTL O00327 R-HSA-400253 Circadian Clock
UKB-a:248 Body mass index (BMI) -0.016203 0.002426 0.573835 2.412682e-11 336107.0 rs7719067 MFAP3 P55082 R-HSA-2129379 Molecules associated with elastic fibres
UKB-a:248 Body mass index (BMI) -0.018964 0.002848 0.759470 2.754229e-11 336107.0 rs10749233 KIAA1598 A0MZ66 R-HSA-437239 Recycling pathway of L1
UKB-a:248 Body mass index (BMI) -0.016462 0.002478 0.385007 3.083188e-11 336107.0 rs35722922 SOCS5 O75159 R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
UKB-a:248 Body mass index (BMI) -0.015881 0.002407 0.506441 4.209204e-11 336107.0 rs7195386 RBBP6 Q7Z6E9 R-HSA-983168 Antigen processing: Ubiquitination & Proteasom...
UKB-a:248 Body mass index (BMI) -0.017556 0.002692 0.276544 7.017784e-11 336107.0 rs7992832 MTIF3 Q9H2K0 R-HSA-5368286 Mitochondrial translation initiation
UKB-a:248 Body mass index (BMI) 0.031266 0.004810 0.066648 8.027864e-11 336107.0 rs60654199 RASA2 Q15283 R-HSA-6802949 Signaling by RAS mutants
UKB-a:248 Body mass index (BMI) 0.031266 0.004810 0.066648 8.027864e-11 336107.0 rs60654199 RASA2 Q15283 R-HSA-5658442 Regulation of RAS by GAPs

Query diagram

Cypher query

MATCH (gwas:Gwas {trait: "Body mass index (BMI)"}) <-[mre_study_snp:MRE_STUDY_SNP]-(snp:Snp)-[snp_gene:SNP_GENE]-> (gene:Gene)-[gene_to_protein:GENE_TO_PROTEIN]->(protein:Protein) -[protein_in_pathway:PROTEIN_IN_PATHWAY]->(pathway:Pathway) WHERE mre_study_snp.pval < 1e-10 AND snp.name is not null AND gene.name is not null RETURN gwas {.id, .trait}, mre_study_snp {.se, .eaf, .pval, .samplesize, .beta}, snp {.name}, gene {.name}, protein {.uniprot_id}, pathway {.reactome_id, .name} ORDER BY mre_study_snp.pval ;

API call

curl -X 'GET' -H 'Accept: */*' -H 'Accept-Encoding: gzip, deflate' -H 'Connection: keep-alive' -H 'User-Agent: python-requests/2.22.0' 'http://api.epigraphdb.org/pathway?trait_name=Body+mass+index+%28BMI%29&pval_threshold=1e-10'

Response data

{
    "query": "MATCH (gwas:Gwas {trait: \"Body mass index (BMI)\"}) <-[mre_study_snp:MRE_STUDY_SNP]-(snp:Snp)-[snp_gene:SNP_GENE]-> (gene:Gene)-[gene_to_protein:GENE_TO_PROTEIN]->(protein:Protein) -[protein_in_pathway:PROTEIN_IN_PATHWAY]->(pathway:Pathway) WHERE mre_study_snp.pval < 1e-10 AND snp.name is not null AND gene.name is not null RETURN gwas {.id, .trait}, mre_study_snp {.se, .eaf, .pval, .samplesize, .beta}, snp {.name}, gene {.name}, protein {.uniprot_id}, pathway {.reactome_id, .name} ORDER BY mre_study_snp.pval ;",
    "results": [
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00306191,
                "eaf": 0.189726,
                "pval": 2.03798038628704e-39,
                "samplesize": 336107.0,
                "beta": -0.0402275
            },
            "snp": {
                "name": "rs6265"
            },
            "gene": {
                "name": "BDNF"
            },
            "protein": {
                "uniprot_id": "P23560"
            },
            "pathway": {
                "name": "MECP2 regulates transcription of neuronal ligands",
                "reactome_id": "R-HSA-9022702"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00241668,
                "eaf": 0.55278,
                "pval": 1.68344913956706e-33,
                "samplesize": 336107.0,
                "beta": 0.0291524
            },
            "snp": {
                "name": "rs4402589"
            },
            "gene": {
                "name": "TMEM219"
            },
            "protein": {
                "uniprot_id": "Q86XT9"
            },
            "pathway": {
                "name": "TP53 Regulates Transcription of Death Receptors and Ligands",
                "reactome_id": "R-HSA-6803211"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254511,
                "eaf": 0.335903,
                "pval": 1.7167221078581e-24,
                "samplesize": 336107.0,
                "beta": 0.0259978
            },
            "snp": {
                "name": "rs34045288"
            },
            "gene": {
                "name": "LRFN2"
            },
            "protein": {
                "uniprot_id": "Q9ULH4"
            },
            "pathway": {
                "name": "Synaptic adhesion-like molecules",
                "reactome_id": "R-HSA-8849932"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00759831,
                "eaf": 0.0257993,
                "pval": 6.44762840643921e-19,
                "samplesize": 336107.0,
                "beta": 0.0675077
            },
            "snp": {
                "name": "rs17024393"
            },
            "gene": {
                "name": "GNAT2"
            },
            "protein": {
                "uniprot_id": "P19087"
            },
            "pathway": {
                "name": "Ca2+ pathway",
                "reactome_id": "R-HSA-4086398"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00759831,
                "eaf": 0.0257993,
                "pval": 6.44762840643921e-19,
                "samplesize": 336107.0,
                "beta": 0.0675077
            },
            "snp": {
                "name": "rs17024393"
            },
            "gene": {
                "name": "GNAT2"
            },
            "protein": {
                "uniprot_id": "P19087"
            },
            "pathway": {
                "name": "Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding",
                "reactome_id": "R-HSA-6814122"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00759831,
                "eaf": 0.0257993,
                "pval": 6.44762840643921e-19,
                "samplesize": 336107.0,
                "beta": 0.0675077
            },
            "snp": {
                "name": "rs17024393"
            },
            "gene": {
                "name": "GNAI3"
            },
            "protein": {
                "uniprot_id": "P08754"
            },
            "pathway": {
                "name": "Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding",
                "reactome_id": "R-HSA-6814122"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00241922,
                "eaf": 0.514078,
                "pval": 7.7374882051481e-18,
                "samplesize": 336107.0,
                "beta": 0.0208148
            },
            "snp": {
                "name": "rs7141420"
            },
            "gene": {
                "name": "NRXN3"
            },
            "protein": {
                "uniprot_id": "Q9Y4C0"
            },
            "pathway": {
                "name": "Neurexins and neuroligins",
                "reactome_id": "R-HSA-6794361"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00241922,
                "eaf": 0.514078,
                "pval": 7.7374882051481e-18,
                "samplesize": 336107.0,
                "beta": 0.0208148
            },
            "snp": {
                "name": "rs7141420"
            },
            "gene": {
                "name": "NRXN3"
            },
            "protein": {
                "uniprot_id": "Q9HDB5"
            },
            "pathway": {
                "name": "Neurexins and neuroligins",
                "reactome_id": "R-HSA-6794361"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.002496,
                "eaf": 0.639151,
                "pval": 1.34865230816678e-16,
                "samplesize": 336107.0,
                "beta": -0.020641
            },
            "snp": {
                "name": "rs2234458"
            },
            "gene": {
                "name": "EFEMP2"
            },
            "protein": {
                "uniprot_id": "O95967"
            },
            "pathway": {
                "name": "Molecules associated with elastic fibres",
                "reactome_id": "R-HSA-2129379"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "Ovarian tumor domain proteases",
                "reactome_id": "R-HSA-5689896"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon",
                "reactome_id": "R-HSA-936964"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "TICAM1-dependent activation of IRF3/IRF7",
                "reactome_id": "R-HSA-9013973"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "TRAF3-dependent IRF activation pathway",
                "reactome_id": "R-HSA-918233"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "Negative regulators of DDX58/IFIH1 signaling",
                "reactome_id": "R-HSA-936440"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
            },
            "gene": {
                "name": "TRAF3"
            },
            "protein": {
                "uniprot_id": "Q13114"
            },
            "pathway": {
                "name": "TRAF3 deficiency - HSE",
                "reactome_id": "R-HSA-5602571"
            }
        },
        {
            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00254468,
                "eaf": 0.666379,
                "pval": 3.0824781017155e-16,
                "samplesize": 336107.0,
                "beta": -0.0207912
            },
            "snp": {
                "name": "rs3803286"
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            "gwas": {
                "trait": "Body mass index (BMI)",
                "id": "UKB-a:248"
            },
            "mre_study_snp": {
                "se": 0.00481001,
                "eaf": 0.0666476,
                "pval": 8.02786387989787e-11,
                "samplesize": 336107.0,
                "beta": 0.0312664
            },
            "snp": {
                "name": "rs60654199"
            },
            "gene": {
                "name": "RASA2"
            },
            "protein": {
                "uniprot_id": "Q15283"
            },
            "pathway": {
                "name": "Regulation of RAS by GAPs",
                "reactome_id": "R-HSA-5658442"
            }
        }
    ]
}