Brain injury

disease

On this page

Also known as brain traumabrain Traumasinjury of brain

Summary

Brain injury (MONDO:0043510) is a disease with 72 GWAS associations across 21 studies and 646 clinical trials. Top therapeutic interventions include amantadine, amitriptyline, and cefotaxime. A subtype of brain disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

GWAS associations: 72
Clinical trials: 646

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain injury
Mondo ID	MONDO:0043510
MeSH	D001930
Anatomy (UBERON)	UBERON:0000955
Is cancer (heuristic)	no

Also known as: brain injury · brain trauma · brain Traumas · injury of brain

Data availability: 72 GWAS associations (21 studies).

Disease family

This is a subtype of brain 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 body system or component › nervous system disorder › central nervous system disorder › brain disorder › brain injury

Subtypes (2): vascular brain injury, traumatic brain injury

Genetics & variants

GWAS landscape

72 GWAS associations across 21 studies. Top hits map to 9 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1940701	4e-13	NCAM1	T	0.04
rs729053	1e-11	LINC01929 - RNA5SP459	C	0.04
rs147515356	2e-11	LINC00375	C	3.54
rs537374948	2e-11	MYL12B - LINC01895	T	3.06
rs429358	3e-11	APOE	T	0.05
rs71149745	5e-11	FOXP2	A	0.04
rs34350548	4e-10		T	0.96
rs4933752	5e-10		T	0.96
rs1539883	6e-10		T	1.04
rs4608411	8e-10		T	1.04
rs79940062	9e-10		A	1.13
rs140930533	1e-09		CAG	0.04
rs4937872	1e-09	LINC02763 - NCAM1-AS2	G	1.04
rs623111	2e-09		A	1.04
rs11332270	3e-09		G	0.03
rs17394072	3e-09		A	0.96
rs138580110	4e-09		A	0.04
rs58436188	6e-09		T	1.04
rs4377571	7e-09	SFRP2 - DCHS2	A	1.04
rs566208700	8e-09		G	0.03
rs201720501	1e-08		T	0.03
rs62033400	1e-08	FTO	A	0.03
rs651350	2e-08		A	0.05
rs9972653	2e-08	FTO	T	0.97
rs148108087	3e-08	LINC01872	A	0.08
rs2243504	3e-08	LINC00926	G	0.97
rs28852987	3e-08		G	0.97
rs12705715	3e-08		G	1.04
rs150122126	3e-08	SLC22A23 - TOMM5P1	?
rs34799259	3e-08		A	0.97

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90444410	Merritt VC	2023	85,613	164,172	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90809463	Merritt VC	2023	85,613	164,172	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444415	Merritt VC	2023	79,684	152,591	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444417	Merritt VC	2023	79,684	152,591	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444413	Merritt VC	2023	15,714	19,756	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444419	Merritt VC	2023	14,073	16,803	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90476971	Verma A	2024	10,560	305,108	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90444414	Merritt VC	2023	10,167	9,063	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444421	Merritt VC	2023	9,389	8,113	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.
GCST90444416	Merritt VC	2023	5,712	11,371	Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	36

MAF distribution

Bucket	Variants
common (>=0.05)	34
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	1

Functional consequences

Consequence	Count
unknown	18
intron_variant	10
intergenic_variant	7
missense_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1940701	11	112998682	T>A,C,G	0.405	intron_variant	NCAM1	4e-13	Tier 4: intronic/intergenic
rs729053	18	55142450	G>C	0.324	intergenic_variant	LINC01929 - RNA5SP459	1e-11	Tier 4: intronic/intergenic
rs147515356	13	85048989	C>G,T	0	intergenic_variant	LINC00375	2e-11	Tier 4: intronic/intergenic
rs537374948	18	3345497	T>C	0	intergenic_variant	MYL12B - LINC01895	2e-11	Tier 4: intronic/intergenic
rs429358	19	44908684	T>C	0.149	missense_variant	APOE	3e-11	Tier 1: coding
rs71149745	7	114416441	A>AAATTTCAT	0.403	intron_variant	FOXP2	5e-11	Tier 4: intronic/intergenic
rs34350548	10	92898269	TAAA>T,TA,TAA,TAAAA,TAAAAA,TAAAAAA	0.362			4e-10	Tier 4: intronic/intergenic
rs4933752	10	92913027	T>A,C	0.308			5e-10	Tier 4: intronic/intergenic
rs1539883	18	55154130	C>G,T	0.335			6e-10	Tier 4: intronic/intergenic
rs4608411	18	55157406	C>T	0.322			8e-10	Tier 4: intronic/intergenic
rs79940062	17	4894615	G>A,T	0.05			9e-10	Tier 4: intronic/intergenic
rs140930533	1	73310888		0.43	non_coding_transcript_exon_variant		1e-09	Tier 4: intronic/intergenic
rs4937872	11	112956992	A>G,T	0.421	intergenic_variant	LINC02763 - NCAM1-AS2	1e-09	Tier 4: intronic/intergenic
rs623111	1	191424549	C>A,G	0.404			2e-09	Tier 4: intronic/intergenic
rs11332270	1	191419686	GA>G,GAA	0.403	intergenic_variant		3e-09	Tier 4: intronic/intergenic
rs17394072	2	222007843	A>C,G	0.493			3e-09	Tier 4: intronic/intergenic
rs138580110	2	78607666		0.316	intergenic_variant		4e-09	Tier 4: intronic/intergenic
rs58436188	1	191415588	TA>T,TAA	0.356	intergenic_variant		6e-09	Tier 4: intronic/intergenic
rs4377571	4	153845527	A>T	0.454	intron_variant	SFRP2 - DCHS2	7e-09	Tier 4: intronic/intergenic
rs566208700				0.436			8e-09	Tier 4: intronic/intergenic
rs201720501	7	115411048	TG>T,TGG,TGGG	0.439			1e-08	Tier 4: intronic/intergenic
rs62033400	16	53777876	A>G	0.372	intron_variant	FTO	1e-08	Tier 4: intronic/intergenic
rs651350	18	55653507	A>C,G	0.124			2e-08	Tier 4: intronic/intergenic
rs9972653	16	53780451	G>T	0.395	intron_variant	FTO	2e-08	Tier 4: intronic/intergenic
rs148108087	19	51278201	G>A	0.053	intron_variant	LINC01872	3e-08	Tier 4: intronic/intergenic
rs2243504	15	57305082	T>C,G	0.462	intron_variant	LINC00926	3e-08	Tier 4: intronic/intergenic
rs28852987	2	78538215	A>C,G	0.382			3e-08	Tier 4: intronic/intergenic
rs12705715	7	110642630	A>C,G,T	0.466			3e-08	Tier 4: intronic/intergenic
rs150122126	6	3641266	C>A		intron_variant	SLC22A23 - TOMM5P1	3e-08	Tier 4: intronic/intergenic
rs34799259	2	143403925	ATTT>A,AT,ATT,ATTTT,ATTTTTTTTTT	0.421			3e-08	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

1 approved, 28 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Baclofen	Approved (phase 4)
Amantadine	Phase 3 (in late-stage trials)
Armodafinil	Phase 3 (in late-stage trials)
Blood, Whole	Phase 3 (in late-stage trials)
Citicoline	Phase 3 (in late-stage trials)
Cyanocobalamin	Phase 3 (in late-stage trials)
Dalteparin Sodium	Phase 3 (in late-stage trials)
Dexanabinol	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Dextran	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Magnesium Sulfate Anhydrous	Phase 3 (in late-stage trials)
Mannitol	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Naloxegol	Phase 3 (in late-stage trials)
Niacinamide	Phase 3 (in late-stage trials)
Nitric Oxide	Phase 3 (in late-stage trials)
Pentobarbital	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Propranolol	Phase 3 (in late-stage trials)
Rivastigmine	Phase 3 (in late-stage trials)
Ronopterin	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Thiopental	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetaminophen, Acetylcysteine, Anakinra, Apomorphine, Baricitinib, Bevacizumab, Bezisterim, Brexanolone, Candesartan Cilexetil, Cannabinol, Clonidine, Cycloserine, Cyclosporine, Darbepoetin Alfa, Dobutamine, Edaravone, Epigalocatechin Gallate, Epoetin Beta, Estrogens, Conjugated, Fentanyl, Glyburide, Ketamine, Methylphenidate, Norepinephrine, Onabotulinumtoxina, Oxygen, Platelets, Pregnenolone Succinate, Sertraline, Sevoflurane, Sildenafil, Somatropin, Tolcapone, Trofinetide, Xenon.

Clinical trials & evidence

Clinical trials

Clinical trials: 646.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	563
PHASE2	29
PHASE4	20
PHASE3	12
PHASE1	8
PHASE1/PHASE2	6
EARLY_PHASE1	5
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06927336	PHASE4	NOT_YET_RECRUITING	The Study on the Efficacy of tDCS Stimulation of the Cerebellum Combined With XingNaoJing Injection in Patients With Consciousness Disorders After Cranial Injury
NCT00035139	PHASE4	COMPLETED	Pediatric Traumatic Brain Injury: Methylphenidate Effects on Early Recovery
NCT00170378	PHASE4	COMPLETED	The Use of Low Molecular Weight Heparin in Traumatic Brain Injury
NCT00178646	PHASE4	COMPLETED	Comparative Efficacy of Three Preparations of Botox-A in Treating Spasticity
NCT00432263	PHASE4	WITHDRAWN	Treatment Of Adult Growth Hormone Deficiency After Traumatic Brain Injury.
NCT00538369	PHASE4	TERMINATED	Combining Observational and Physiologic Sedation Assessment Tools
NCT00555009	PHASE4	TERMINATED	Treatment Of Adult Growth Hormone Deficiency After Traumatic Brain Injury
NCT00638053	PHASE4	TERMINATED	A Study to Evaluate the Efficacy of Somatropin in Adults With Growth Hormone Deficiency Caused by Trauma and/or Head Injury
NCT00809055	PHASE4	COMPLETED	MRI and Neurodevelopment in Preterm Infants Following Administration of High-Dose Caffeine
NCT01137773	PHASE4	TERMINATED	Normoglycemia and Neurological Outcome
NCT01201863	PHASE4	COMPLETED	Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy
NCT01207050	PHASE4	UNKNOWN	Effect of Rozerem on Sleep Among People With Traumatic Brain Injury
NCT01214070	PHASE4	TERMINATED	Functional Vision in TBI
NCT02052024	PHASE4	COMPLETED	Myobloc Atrophy Study
NCT02058940	PHASE4	COMPLETED	Intravenous Exenatide in Patients With Acute Brain Injury
NCT02123355	PHASE4	UNKNOWN	The Effect of Dexmedetomidine to Cognition of Geriatrics in Prolonged Surgery
NCT02161055	PHASE4	UNKNOWN	Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury
NCT03648021	PHASE4	COMPLETED	The Effect of Paracetamol on Brain Temperature
NCT04386525	PHASE4	UNKNOWN	Omega 3 and Ischemic Stroke; Fish Oil as an Option
NCT04508244	PHASE4	UNKNOWN	Beta Blocker Use In Traumatic Brain Injury Based On The High-Sensitive Troponin T Status
NCT04499755	PHASE3	RECRUITING	Efficacy of Nucleo CMP Forte in Traumatic Brain Injury in Pediatrics
NCT05008926	PHASE3	RECRUITING	The NIPA Study Naloxegol Administration to Prevent Opioids Induced Gastrointestinal Motility Disturbance in Brain Injured PAtients
NCT06819592	PHASE3	RECRUITING	PRophylaxis Against Early VENTilator-associated Infections in Acute Brain Injury
NCT00004730	PHASE3	COMPLETED	Magnesium Sulfate For Brain Injury
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00155987	PHASE3	COMPLETED	The DECRA Trial: Early Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury
NCT00755209	PHASE3	COMPLETED	Tranexamic Acid for Preventing Progressive Intracranial Haemorrhage in Traumatic Brain Injury
NCT00878631	PHASE2/PHASE3	COMPLETED	Feasibility Trial of Traumatic Brain Injured Patients Randomized in the Prehospital Setting to Either Hypertonic Saline and Dextran Versus Normal Saline
NCT01002677	PHASE2/PHASE3	COMPLETED	Behavioral Trial Studying Programmed Training to Improve Advocacy Skills for Individuals With Traumatic Brain Injury
NCT01068522	PHASE3	UNKNOWN	Study to Improve Outcomes for Survivors of Traumatic Brain Injury in Latin America
NCT01143064	PHASE3	COMPLETED	Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury
NCT02639481	PHASE3	COMPLETED	Erigo®Pro Coma Outcome Study - Study on the Effectiveness of a Robotic Tilt Table Device for Recovery of Consciousness
NCT02697786	PHASE3	UNKNOWN	Neuromonitoring in Patients During Aortic Valve Replacement
NCT03339505	PHASE3	COMPLETED	Effect of Antisecretory Factor, Given as a Food Supplement to Adult Patients With Severe Traumatic Brain Injury
NCT03851809	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of Wendan Decoction in Acute Moderated to Severe Brain Injury
NCT04696523	PHASE2	RECRUITING	Effect of Xenon on Brain Injury After Aneurysmal Subarachnoid Hemorrhage
NCT07414537	PHASE2	NOT_YET_RECRUITING	Remotely Administered tDCS to Improve Cognitive Function in Veterans With mTBI and PTSD Principal Investigator
NCT00336466	PHASE2	COMPLETED	The Erythropoietin NeuroProtective Effect: Assessment in CABG Surgery (TENPEAKS)
NCT00538616	PHASE1/PHASE2	COMPLETED	Precedex Versus Propofol-Awakening for Reducing Brain Injury Expansion
NCT00589953	PHASE2	TERMINATED	High-Dose Erythropoietin in Extremely Premature Infants to Prevent/Attenuate Brain Injury: A Phase II Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMANTADINE	4	3
AMITRIPTYLINE	4	3
CEFOTAXIME	4	3
DEXMEDETOMIDINE	4	3
FLUVOXAMINE	4	3
METHYLPHENIDATE	4	3
PRAZOSIN	4	3
PROPRANOLOL	4	3
SOMATROPIN	4	3
INSULIN HUMAN	4	2
MAGNESIUM SULFATE	4	2
TOLCAPONE	4	2
TROFINETIDE	4	2
APOMORPHINE	4	1
CAFFEINE CITRATE	4	1
CEFTRIAXONE	4	1
COSYNTROPIN	4	1
ENOXAPARIN SODIUM	4	1
EXENATIDE	4	1
FERUMOXYTOL	4	1
INDOMETHACIN	4	1
INULIN	4	1
ISOPROTERENOL	4	1
METHADONE	4	1
METYRAPONE	4	1
MIRTAZAPINE	4	1
NALOXEGOL	4	1
RAMELTEON	4	1
REMIFENTANIL	4	1
RIMABOTULINUMTOXINB	4	1

Drugs: Amantadine, Amitriptyline, Cefotaxime, Dexmedetomidine, Fluvoxamine, Methylphenidate, Prazosin, Propranolol, Somatropin, Insulin Human, Magnesium, Tolcapone, Trofinetide, Apomorphine, Caffeine, Ceftriaxone, Cosyntropin, Enoxaparin, Exenatide, Ferumoxytol, Indomethacin, Inulin, Isoproterenol, Methadone, Metyrapone, Mirtazapine, Naloxegol, Ramelteon, Remifentanil, Rimabotulinumtoxinb