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Atlas / Disease / Substance abuse

Substance abuse

disease
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Summary

Substance abuse (MONDO:0002491) is a disease (an umbrella term covering 8 Mondo subtypes) with 1 cohort gene (591 GWAS associations across 9 studies) and 289 clinical trials. Top therapeutic interventions include rivastigmine, quetiapine, and doxazosin.

At a glance

  • Umbrella term: 8 Mondo subtypes
  • Cohort genes: 1
  • GWAS associations: 591
  • Clinical trials: 289

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namesubstance abuse
Mondo IDMONDO:0002491
DOIDDOID:302
SNOMED CT66214007
UMLSC0740858
MedGen152849
Is cancer (heuristic)no

Data availability: 591 GWAS associations (9 studies).

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › substance-related disorder › substance abuse

Related subtypes (3): substance dependence, substance withdrawal syndrome, alcohol-related disorders

Subtypes (8): opioid abuse, antidepressant type abuse, hallucinogen abuse, alcohol abuse, amphetamine abuse, cocaine abuse, barbiturate abuse, phencyclidine abuse

Genetics & variants

GWAS landscape

591 GWAS associations across 9 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs99195587e-59NCAM1T0.02
rs9931375e-53CADM2C0.02
rs2660582e-38TMEM182 - CRLF3P1C0.02
rs286063701e-33BORCS7-ASMT - CNNM2C0.01
rs10047871e-32LINC01833G0.01
rs64527854e-32TMEM161B-DTC0.01
rs129075461e-31SEMA6DG0.02
rs48566052e-30CADM2G0.01
rs9517405e-30PTPRFG0.01
rs13812878e-30LINC01550 - LINC02295C0.01
rs4588061e-29REV3L, MFSD4BC0.02
rs120898152e-29BARHL2 - LINC02609G0.01
rs26687339e-29RNA5SP94 - MIR4432HGC0.01
rs23368952e-27TENM2G0.01
rs117207033e-27FOXP1C0.01
rs43498862e-26SDK1C0.01
rs14765353e-26FOXP2C0.01
rs104272553e-26RPL6P5 - METAP2P1C0.01
rs62652e-24BDNF-AS, BDNFC0.01
rs76759163e-24PCDH7C0.01
rs129708163e-24DCCG0.01
rs129026369e-24SEMA6DC0.01
rs47021e-23FURING0.01
rs726788592e-23RNU6-289P - RPL36AP23C0.02
rs64609442e-23MAD1L1C0.01
rs42406715e-23XKR6G0.01
rs25263848e-23SEMA3F-AS1C0.01
rs40744421e-22LINC01830G0.01
rs72415721e-22KCNG2G0.02
rs28653032e-22LSAMP - IGSF11G0.01

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST010542Jang SK202053,2931,475,951Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder.
GCST90727236Kim HI20263,63240,394Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST008414Demontis D20192,38748,985Genome-wide association study implicates CHRNA2 in cannabis use disorder.
GCST008415Demontis D20192,3870Genome-wide association study implicates CHRNA2 in cannabis use disorder.
GCST90027269Martinez-Magana JJ20211,1651,487Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.
GCST90027271Martinez-Magana JJ20216041,487Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.
GCST90134639Chen W202200Genetic predispositions to psychiatric disorders and the risk of COVID-19.
GCST90061435Karlsson Linner R202100Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.
GCST010280Barr PB202000A Family-Based Genome Wide Association Study of Externalizing Behaviors.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR3
Tier 3: regulatory1
Tier 4: intronic/intergenic44

MAF distribution

BucketVariants
common (>=0.05)50
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant35
intergenic_variant8
missense_variant2
3_prime_UTR_variant1
non_coding_transcript_exon_variant1
5_prime_UTR_variant1
splice_region_variant1
TF_binding_site_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs991955811113006687T>A,G0.387intron_variantNCAM17e-59Tier 4: intronic/intergenic
rs993137385449885C>G,T0.383intron_variantCADM25e-53Tier 4: intronic/intergenic
rs2660582103469970C>A,G,T0.472intron_variantTMEM182 - CRLF3P12e-38Tier 4: intronic/intergenic
rs2860637010102911075C>A0.338intron_variantBORCS7-ASMT - CNNM21e-33Tier 4: intronic/intergenic
rs1004787244931952G>A,C,T0.467intron_variantLINC018331e-32Tier 4: intronic/intergenic
rs6452785588389683C>G,T0.468intron_variantTMEM161B-DT4e-32Tier 4: intronic/intergenic
rs129075461547392083G>A0.204intron_variantSEMA6D1e-31Tier 4: intronic/intergenic
rs4856605385858431G>A,C,T0.309intron_variantCADM22e-30Tier 4: intronic/intergenic
rs951740143546066G>A0.383intron_variantPTPRF5e-30Tier 4: intronic/intergenic
rs13812871498131215C>T0.457intron_variantLINC01550 - LINC022958e-30Tier 4: intronic/intergenic
rs4588066111354825C>G,T0.178intron_variantREV3L, MFSD4B1e-29Tier 4: intronic/intergenic
rs12089815190724376G>A,C,T0.453intron_variantBARHL2 - LINC026092e-29Tier 4: intronic/intergenic
rs2668733260259881C>T0.365intron_variantRNA5SP94 - MIR4432HG9e-29Tier 4: intronic/intergenic
rs23368955167563690G>A0.352intron_variantTENM22e-27Tier 4: intronic/intergenic
rs11720703371011489C>G,T0.471intron_variantFOXP13e-27Tier 4: intronic/intergenic
rs434988673330406C>A,T0.462intron_variantSDK12e-26Tier 4: intronic/intergenic
rs14765357114430980C>A,G,T0.451intron_variantFOXP23e-26Tier 4: intronic/intergenic
rs104272552145367955C>T0.473intergenic_variantRPL6P5 - METAP2P13e-26Tier 4: intronic/intergenic
rs62651127658369C>A,G,T0.186missense_variantBDNF-AS, BDNF2e-24Tier 1: coding
rs7675916431142196C>T0.287intron_variantPCDH73e-24Tier 4: intronic/intergenic
rs129708161852497489G>A0.402intron_variantDCC3e-24Tier 4: intronic/intergenic
rs129026361547679254C>G,T0.489intron_variantSEMA6D9e-24Tier 4: intronic/intergenic
rs47021590883330G>A,C0.4423_prime_UTR_variantFURIN1e-23Tier 2: splice/UTR
rs726788594111485805C>T0.167intergenic_variantRNU6-289P - RPL36AP232e-23Tier 4: intronic/intergenic
rs646094471836563C>G,T0.408intron_variantMAD1L12e-23Tier 4: intronic/intergenic
rs4240671810910238G>A0.491intron_variantXKR65e-23Tier 4: intronic/intergenic
rs2526384350143703C>T0.344intron_variantSEMA3F-AS18e-23Tier 4: intronic/intergenic
rs4074442222331242G>A,C0.397intron_variantLINC018301e-22Tier 4: intronic/intergenic
rs72415721879820712G>A,T0.199intron_variantKCNG21e-22Tier 4: intronic/intergenic
rs28653033118074139G>A,C,T0.15intron_variantLSAMP - IGSF112e-22Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CHRNA2Orphanet:98784Sleep-related hypermotor epilepsy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CHRNA2HGNC:1956ENSG00000120903Q15822Neuronal acetylcholine receptor subunit alpha-2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CHRNA2Neuronal acetylcholine receptor subunit alpha-2Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CHRNA2Other/UnknownnoNicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
cervix squamous epithelium1
gingival epithelium1
primordial germ cell in gonad1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CHRNA2143tissue_specificyescervix squamous epithelium, primordial germ cell in gonad, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CHRNA2982

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CHRNA2Q158221

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Highly calcium permeable nicotinic acetylcholine receptors11268.9×0.002CHRNA2
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors11038.2×0.002CHRNA2
Presynaptic nicotinic acetylcholine receptors1951.7×0.002CHRNA2
Acetylcholine binding and downstream events1815.7×0.002CHRNA2
Postsynaptic nicotinic acetylcholine receptors1815.7×0.002CHRNA2
Neurotransmitter receptors and postsynaptic signal transmission1100.2×0.013CHRNA2
Transmission across Chemical Synapses176.1×0.015CHRNA2
Neuronal System144.3×0.023CHRNA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
modulation of inhibitory postsynaptic potential116852.0×7e-04CHRNA2
cellular response to nicotine12106.5×0.003CHRNA2
synaptic transmission, cholinergic1802.5×0.004CHRNA2
acetylcholine receptor signaling pathway1624.1×0.004CHRNA2
neuromuscular synaptic transmission1601.9×0.004CHRNA2
membrane depolarization1510.7×0.004CHRNA2
presynaptic modulation of chemical synaptic transmission1455.5×0.004CHRNA2
response to nicotine1421.3×0.004CHRNA2
regulation of synaptic plasticity1259.3×0.005CHRNA2
monoatomic ion transmembrane transport1208.1×0.006CHRNA2
monoatomic ion transport1156.0×0.007CHRNA2
signal transduction116.1×0.062CHRNA2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
CHRNA2VARENICLINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
CHRNA244

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VARENICLINE4CHRNA2
MECAMYLAMINE4CHRNA2
NICOTINE4CHRNA2
ALTINICLINE2CHRNA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
CHRNA240Binding:37, Functional:2, ADMET:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
VARENICLINE4CHRNA2
MECAMYLAMINE4CHRNA2
NICOTINE4CHRNA2
ALTINICLINE2CHRNA2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CHRNA2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 289.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified191
PHASE228
PHASE124
PHASE1/PHASE214
PHASE413
PHASE311
PHASE2/PHASE35
EARLY_PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00130923PHASE4COMPLETEDRisperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00156715PHASE4COMPLETEDEfficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00169026PHASE4TERMINATEDAlcoholism and Schizophrenia: Effects of Clozapine
NCT00203528PHASE4COMPLETEDDivalproex ER vs. Risperidone for Bipolar Disorder With Comorbid Substance Use Disorder
NCT00208143PHASE4COMPLETEDSeroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia
NCT00208169PHASE4COMPLETEDAbilify Therapy for Reducing Comorbid Substance Abuse
NCT00208195PHASE4COMPLETEDDepakote ER Therapy for Mania Comorbid With Substance Abuse
NCT00223197PHASE4COMPLETEDPregnenolone Trial for Depression in Bipolar Disorders or Recurrent Major Depressive Disorder With Substance Abuse
NCT00484692PHASE4COMPLETEDRandomized Trial of Ultrashort Psychotherapy vs Sustained-Release Bupropion for Smoking Cessation
NCT00798538PHASE4COMPLETEDIntegration of Buprenorphine Into HIV Clinical Settings - Primary Care Model (PCM)
NCT01155544PHASE4WITHDRAWNImproving Outcomes in Psychosis Associated With Substance Use Using Aripiprazole
NCT01514630PHASE4COMPLETEDCreatine as a Treatment Option for Depression in Methamphetamine Using Females
NCT04170738PHASE4COMPLETEDBrain Indices of Stimulant Treatment in Drug-Naive Youth at Risk for Substance Use Disorder
NCT00095303PHASE3COMPLETEDBrief Strategic Family Therapy for Adolescent Drug Abusers
NCT00264797PHASE3COMPLETEDAttention Deficit Hyperactivity Disorder (ADHD) in Adolescents With Substance Use Disorders (SUD)
NCT00273845PHASE2/PHASE3COMPLETEDReducing Barriers to Drug Abuse Treatment Services
NCT00375102PHASE2/PHASE3COMPLETEDAcupuncture and the Relaxation Response for Substance Abuse
NCT00447720PHASE3COMPLETEDHIV Prevention Among Substance Abusing SMI
NCT00729391PHASE2/PHASE3COMPLETEDWomen-Focused HIV Prevention in the Western Cape
NCT01189214PHASE3COMPLETEDPsychopharmacotherapy in Multiple Substances Abuse
NCT01228890PHASE3WITHDRAWNPrimary Care Internet-Based Depression Prevention for Adolescents (CATCH-IT)
NCT01372033PHASE3COMPLETEDEffects of Manualized Treatment in a Seamless System
NCT01381133PHASE3COMPLETEDAdolescent Outpatient and Continuing Care Study
NCT01523444PHASE3WITHDRAWNAdvancing Adolescent Screening and Brief Intervention Protocols in Primary Care Settings
NCT01573416PHASE3COMPLETEDEffectiveness of a Brief Intervention for Substances Consumption Linked to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): A Randomized Control Trial in Chilean Primary Care.
NCT02111798PHASE2/PHASE3COMPLETEDBupropion-Enhanced Contingency Management (CM) for Cocaine Dependence
NCT03918850PHASE3COMPLETEDMedication Treatment for Opioid Use Disorder in Expectant Mothers
NCT04556552PHASE3COMPLETEDNon-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
NCT04603781PHASE2/PHASE3SUSPENDEDCBD Oil for Reducing Emotional Impact of COVID-19
NCT06788587PHASE2RECRUITINGFeasibility of Long-term, High-dose Stimulant for Methamphetamine Use Disorder
NCT00105768PHASE1/PHASE2COMPLETEDEffectiveness of Advisor-Teller Money Manager
NCT00280228PHASE2COMPLETEDHome Based Treatment for Drug Use in Early Adolescents
NCT00288886PHASE2COMPLETEDReinforcement of Abstinence and Continuing Care in Substance Abuse Treatment
NCT00316303PHASE2COMPLETEDEffectiveness of the Screen, Test, Immunize, Reduce Risk, and Refer (STIRR) Intervention for People With Both a Mental and Substance Abuse Disorder
NCT00318409PHASE2COMPLETEDAcceptability of Pharmacologic Treatment for Methamphetamine Dependence Among MSM
NCT00319241PHASE2COMPLETEDRelational Parenting Group for Opioid-addicted Mothers
NCT00432926PHASE2COMPLETEDBehavior Change and Maintenance Intervention for HIV+ MSM Methamphetamine Users
NCT00497055PHASE2COMPLETEDAripiprazole Treatment for Methamphetamine Dependence Among High-risk Individuals
NCT00497081PHASE2COMPLETEDMirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors
NCT00536900PHASE2COMPLETEDClinical Trial of Abstinence-Linked Money Management

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
RIVASTIGMINE46
QUETIAPINE44
DOXAZOSIN43
PERINDOPRIL43
RISPERIDONE43
ATOMOXETINE42
ARIPIPRAZOLE41
CABERGOLINE41
DEXTROAMPHETAMINE41
DIVALPROEX SODIUM41
IBUDILAST41
MEMANTINE41
METHAMPHETAMINE41
METHYLPHENIDATE41
MIRTAZAPINE41
OXYGEN41
PRAMIPEXOLE41
CITICOLINE32
CANDESARTAN31
CARISBAMATE31
DEXPRAMIPEXOLE31
MICROCRYSTALLINE CELLULOSE31
OMEGA-3 FATTY ACIDS31
PREGNENOLONE SUCCINATE31
HUPERZINE A21
NP-1067911
PREGNENOLONE11
RTI-33611
CHEMBL454703202
CHEMBL527595001

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 70

This page pulls from 70 datasets indexed by BioBTree:

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