Substance-related disorder

Summary

Substance-related disorder (MONDO:0002494) is a disease with 1,125 GWAS associations across 31 studies and 349 clinical trials. Top therapeutic interventions include doxazosin, levomethadyl acetate, and buprenorphine. A subtype of psychiatric disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 1,125
• Clinical trials: 349

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	substance-related disorder
Mondo ID	MONDO:0002494
MeSH	D019966
DOID	DOID:303
ICD-10-CM	F10-F19
NCIT	C92203
UMLS	C0236969
MedGen	66746
Is cancer (heuristic)	no

Also known as: substance induced mood disorders · substance-related disorder

Data availability: 1,125 GWAS associations (31 studies).

Disease family

This is a subtype of psychiatric disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

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

Related subtypes (13): sexual disorder, dissociative disorder, impulse control disorder, personality disorder, cognitive disorder, factitious disorder, somatoform disorder, mental disorder, eating disorder, enuresis, Alice in Wonderland syndrome, catatonia, body integrity dysphoria

Subtypes (4): substance abuse, substance dependence, substance withdrawal syndrome, alcohol-related disorders

Genetics & variants

GWAS landscape

1,125 GWAS associations across 31 studies. Top hits map to 20 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs472140	4e-43	CAMKMT - LINC01833	?	0.01
rs61902812	3e-32	DRD2 - TMPRSS5	A
rs9928094	7e-32	FTO	?	0.01
rs7625857	4e-29	BSN	T	11.21
rs12031120	1e-28	LINC01360 - LINC02238	A	11.12
rs1116313	2e-28	DRD2	A
rs1076563	7e-28	DRD2	A	10.95
rs13107325	8e-28	SLC39A8	T	10.94
rs9812360	1e-27	RHOA	T	10.89
rs61687445	1e-27	DRD2 - TMPRSS5	A
rs6589386	2e-26	DRD2 - TMPRSS5	T	10.63
rs7122246	9e-26	DRD2	A	10.5
rs999851	5e-25	NCAM1	A
rs2734838	3e-24	DRD2	A	10.17
rs56137030	4e-24	FTO	A	10.12
rs4439551	5e-24	NCAM1	T	10.11
rs13135092	1e-23	SLC39A8	A
rs13109404	4e-23	BANK1	T	9.89
rs6846266	6e-23	BTF3P13 - EIF4E	?	0.01
rs4837011	2e-22	PPP6C	T	9.73
rs6794924	4e-22	CIMIP7 - IHO1	A	9.66
rs7519259	5e-22	PDE4B	A	9.65
rs1229984	3e-21	ADH1B	T	9.48
rs1944678	4e-21	SORL1 - RNU6-256P	A
rs6589894	8e-21	SORL1 - RNU6-256P	T	9.35
rs175979	2e-20	SEMA6D	A	9.29
rs6421482	2e-20	PDE4B	A	9.28
rs10736470	3e-20	DRD2 - TMPRSS5	A	9.23
rs61903076	4e-20	DRD2 - TMPRSS5	A
rs7528128	9e-20	LINC01360 - LINC02238	A	9.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476516	Verma A	2024	52,014	378,515	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480765	Verma A	2024	32,336	82,798	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481847	Verma A	2024	32,336	82,798	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90448551	LaBianca S	2023	20,065	20,509	Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.
GCST90102283	Meng P	2022	17,604	359,202	Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data.
GCST90481845	Verma A	2024	9,807	46,967	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90042762	Jiang L	2021	8,803	137,303	A generalized linear mixed model association tool for biobank-scale data.
GCST90078396	Backman JD	2021	8,298	129,860	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082382	Backman JD	2021	8,298	129,860	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90042766	Jiang L	2021	3,406	4,757	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	34
intergenic_variant	12
missense_variant	2
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs472140	2	44912765	C>T	0.05	regulatory_region_variant	CAMKMT - LINC01833	4e-43	Tier 3: regulatory
rs61902812	11	113503698	C>A,T	0.05	intergenic_variant	DRD2 - TMPRSS5	3e-32	Tier 4: intronic/intergenic
rs9928094	16	53765993	A>G,T	0.05	intron_variant	FTO	7e-32	Tier 4: intronic/intergenic
rs7625857	3	49559029	C>T	0.05	intron_variant	BSN	4e-29	Tier 4: intronic/intergenic
rs12031120	1	73395138	G>A	0.05	intron_variant	LINC01360 - LINC02238	1e-28	Tier 4: intronic/intergenic
rs1116313	11	113425385	A>G,T	0.05	intron_variant	DRD2	2e-28	Tier 4: intronic/intergenic
rs1076563	11	113425187	A>C,T	0.05	intron_variant	DRD2	7e-28	Tier 4: intronic/intergenic
rs13107325	4	102267552	C>A,T	0.05	missense_variant	SLC39A8	8e-28	Tier 1: coding
rs9812360	3	49364918	T>A,C,G	0.05	intron_variant	RHOA	1e-27	Tier 4: intronic/intergenic
rs61687445	11	113567370	C>A	0.05	intergenic_variant	DRD2 - TMPRSS5	1e-27	Tier 4: intronic/intergenic
rs6589386	11	113573031	C>G,T	0.05	intergenic_variant	DRD2 - TMPRSS5	2e-26	Tier 4: intronic/intergenic
rs7122246	11	113433735	G>A	0.05	intron_variant	DRD2	9e-26	Tier 4: intronic/intergenic
rs999851	11	113019124	A>C,G	0.05	intron_variant	NCAM1	5e-25	Tier 4: intronic/intergenic
rs2734838	11	113415779	A>C,G,T	0.05	intron_variant	DRD2	3e-24	Tier 4: intronic/intergenic
rs56137030	16	53791993	G>A,T	0.05	intron_variant	FTO	4e-24	Tier 4: intronic/intergenic
rs4439551	11	112995184	T>C,G	0.05	intron_variant	NCAM1	5e-24	Tier 4: intronic/intergenic
rs13135092	4	102276925	A>G	0.05	intron_variant	SLC39A8	1e-23	Tier 4: intronic/intergenic
rs13109404	4	101975434	T>G	0.05	intron_variant	BANK1	4e-23	Tier 4: intronic/intergenic
rs6846266	4	98870160	A>G	0.05	intergenic_variant	BTF3P13 - EIF4E	6e-23	Tier 4: intronic/intergenic
rs4837011	9	125160735	G>T	0.05	intron_variant	PPP6C	2e-22	Tier 4: intronic/intergenic
rs6794924	3	49194581	G>A,C	0.05	intergenic_variant	CIMIP7 - IHO1	4e-22	Tier 4: intronic/intergenic
rs7519259	1	65969060	G>A	0.05	intron_variant	PDE4B	5e-22	Tier 4: intronic/intergenic
rs1229984	4	99318162	T>A,C,G	0.05	missense_variant	ADH1B	3e-21	Tier 1: coding
rs1944678	11	121775872	C>A,G,T	0.05	intron_variant	SORL1 - RNU6-256P	4e-21	Tier 4: intronic/intergenic
rs6589894	11	121765352	C>T	0.05	intron_variant	SORL1 - RNU6-256P	8e-21	Tier 4: intronic/intergenic
rs175979	15	47382615	A>C,G,T	0.05	intron_variant	SEMA6D	2e-20	Tier 4: intronic/intergenic
rs6421482	1	65954222	A>G,T	0.05	intron_variant	PDE4B	2e-20	Tier 4: intronic/intergenic
rs10736470	11	113547649	G>A,C	0.05	intergenic_variant	DRD2 - TMPRSS5	3e-20	Tier 4: intronic/intergenic
rs61903076	11	113682511	A>G	0.05	intergenic_variant	DRD2 - TMPRSS5	4e-20	Tier 4: intronic/intergenic
rs7528128	1	73429486	G>A,C	0.05	intron_variant	LINC01360 - LINC02238	9e-20	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

2 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Buprenorphine	Approved (phase 4)
Oxycodone	Approved (phase 4)
Memantine	Phase 3 (in late-stage trials)
Reslizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atomoxetine, Bupropion, Lisdexamfetamine, Mirtazapine, Oxytocin, Propranolol, Varenicline.

Clinical trials & evidence

Clinical trials

Clinical trials: 349.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	198
PHASE2	57
PHASE1	30
PHASE3	26
PHASE4	22
PHASE1/PHASE2	9
PHASE2/PHASE3	4
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00000218	PHASE4	COMPLETED	Pharmacotherapy and Intensive Treatment - 2
NCT00000321	PHASE4	COMPLETED	Methamphetamine Abuse Treatment in Patients With AIDS - 1
NCT00000343	PHASE4	COMPLETED	Brain Changes in Stimulant Dependent Subjects - 8
NCT00000388	PHASE4	COMPLETED	Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA)
NCT00015236	PHASE4	COMPLETED	Modeling Impaired Judgement in Cocaine Abusers - 6
NCT00015275	PHASE4	COMPLETED	Pathophysiological Subtyping of Abnormalities in Cocaine Dependence - 9
NCT00015301	PHASE4	COMPLETED	Methylphenidate Raclopride Positron Emission Tomography (PET) Test - 11
NCT00015340	PHASE4	COMPLETED	Buprenorphine/Naloxone in the Treatment of Heroin Dependence - 14
NCT00061113	PHASE4	COMPLETED	Substance Dependent Teens - Impact of Treating Depression Study 1 - 1
NCT00137306	PHASE4	COMPLETED	Facilitating the Adoption of Evidence-Based Depression Management in Substance Use Treatment Programs
NCT00194480	PHASE4	COMPLETED	Treatment of Acute Hepatitis C Virus Infection With Pegylated Interferon in Injection Drug Users
NCT00218322	PHASE4	COMPLETED	Effectiveness of ATMX in Treating Adolescents With ADHD and SUD
NCT00232336	PHASE4	COMPLETED	Quetiapine for Cocaine Use and Cravings
NCT00317460	PHASE4	COMPLETED	Buprenorphine and Integrated HIV Care
NCT00798538	PHASE4	COMPLETED	Integration of Buprenorphine Into HIV Clinical Settings - Primary Care Model (PCM)
NCT00944554	PHASE4	COMPLETED	Relapse Prevention With Varenicline
NCT01027754	PHASE4	COMPLETED	Smoking Cessation Treatment for Methadone Maintenance Patients
NCT01563718	PHASE4	COMPLETED	Pre-Release VIVITROL for Opioid Dependent Inmates
NCT01936857	PHASE4	COMPLETED	Buprenorphine to Improve HIV Care Engagement and Outcomes
NCT02101840	PHASE4	COMPLETED	Abuse Liability of Controlled-Release Oxycodone Formulations
NCT02423018	PHASE4	TERMINATED	Abuse Liability of Pregabalin and Its Effects on Benzodiazepine Withdrawal Symptoms
NCT03075501	PHASE4	COMPLETED	Interactions Between Drug Effects and Environments II
NCT06387290	PHASE3	RECRUITING	Optimizing Chronic Pain Care With Mindfulness and Chronic Pain Management Visits
NCT00000216	PHASE3	COMPLETED	Buprenorphine Maintenance for Cocaine Abusing Opioid Addicts - 1
NCT00000311	PHASE3	COMPLETED	Combining Behavioral Treatment With Agonist Maintenance - 1
NCT00015171	PHASE3	COMPLETED	Buprenorphine and Naloxone for the Treatment of Opiate Dependence - 1
NCT00032981	PHASE3	COMPLETED	Motivational Enhancement to Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse - 1
NCT00032994	PHASE3	COMPLETED	Motivational Interviewing to Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse - 1
NCT00033007	PHASE3	COMPLETED	Motivational Incentives for Enhanced Drug Abuse Recovery: Drug Free Clinics - 1
NCT00033020	PHASE3	COMPLETED	Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone Clinics. - 1
NCT00067171	PHASE3	COMPLETED	Telephone Enhancement Procedure for Continuing Care - 1
NCT00078143	PHASE3	COMPLETED	Motivational Enhancement Therapy to Improve Treatment Utilization in Pregnant Substance Users - 1
NCT00078156	PHASE3	COMPLETED	Women’s Treatment for Trauma and Substance Use Disorders - 1
NCT00078169	PHASE3	COMPLETED	Motivational Enhancement for Spanish Speaking Individuals - 1
NCT00102362	PHASE3	COMPLETED	Job-Seekers Training for Patients With Drug Dependence - 1
NCT00183768	PHASE3	COMPLETED	Cognitive Behavioral Therapy Combined With Antidepressants to Reduce HIV Risk and Drug Relapse Among Depressed Intravenous Drug Users
NCT00228007	PHASE3	COMPLETED	Antidepressant Medication for Reducing HIV Risk Behavior in Depressed Intravenous Drug Users
NCT00264329	PHASE3	COMPLETED	Transitional Case Management Study
NCT00316277	PHASE3	COMPLETED	Prescription Opioid Addiction Treatment Study (POATS)
NCT00336180	PHASE2/PHASE3	COMPLETED	Adolescent Drug and HIV Prevention in South Africa

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOXAZOSIN	4	6
LEVOMETHADYL ACETATE	4	6
BUPRENORPHINE	4	5
NALOXONE	4	5
VARENICLINE	4	4
AMANTADINE	4	3
CARBAMAZEPINE	4	3
DESIPRAMINE	4	3
DEXTROMETHORPHAN	4	3
FLUOXETINE	4	3
NEFAZODONE	4	3
NITROUS OXIDE	4	3
PERGOLIDE	4	3
RIVASTIGMINE	4	3
CLONIDINE	4	2
ISOFLURANE	4	2
LISDEXAMFETAMINE DIMESYLATE	4	2
LOFEXIDINE	4	2
ATOMOXETINE HYDROCHLORIDE	4	1
CABERGOLINE	4	1
CLOZAPINE	4	1
COCAINE	4	1
CYCLOSERINE	4	1
DEXTROAMPHETAMINE	4	1
FLUMAZENIL	4	1
FLUVOXAMINE	4	1
FLUVOXAMINE MALEATE	4	1
HYDROXYZINE	4	1
HYDROXYZINE HYDROCHLORIDE	4	1
LEVAMFETAMINE	4	1