Sleep disorder

Summary

Sleep disorder (MONDO:0100081) is a disease (an umbrella term covering 5 Mondo subtypes) with 22 GWAS associations across 75 studies and 666 clinical trials. Top therapeutic interventions include melatonin, zolpidem, and suvorexant. A subtype of disease by developmental or physiological process — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Umbrella term: 5 Mondo subtypes
• GWAS associations: 22
• Clinical trials: 666

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sleep disorder
Mondo ID	MONDO:0100081
EFO	EFO:0008568
NCIT	C3376
UMLS	C0851578
MedGen	208862
Is cancer (heuristic)	no

Also known as: disturbances, sleep · sleep disturbance · sleep disturbances

Data availability: 22 GWAS associations (75 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › sleep disorder

Related subtypes (11): psychiatric disorder, metabolic disease, premature aging syndrome, disorder of development or morphogenesis, inflammatory disease, disorder of glycosylation, ulcer disease, mitochondrial disease, perinatal disease, obstetric disorder, disease by molecular mechanism

Subtypes (5): sleep-wake disorder, insomnia, nocturnal paroxysmal dystonia, parasomnia, sleepwalking type, parasomnia, sleep terrors type

Genetics & variants

GWAS landscape

22 GWAS associations across 75 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs113851554	2e-65	MEIS1	G	0.2
rs13219518	2e-17	BTBD9	A	0.05
chr1:107187880	5e-15		A	0.04
chr17:44408004	2e-12		A	0.06
chr9:140262424	3e-12		C	0.07
chr11:27653220	1e-11		A	0.04
rs13107325	3e-11	SLC39A8	C	0.06
rs429358	4e-11	APOE	T	0.06
rs13234969	4e-11	TMEM106B	T	0.04
chr4:105124090	4e-09		G	0.08
chr2:61223281	1e-08		C	1.41
chr3:132764586	1e-08		T	2.73
chr18:15384806	2e-08		T	2.71
chr9:30687207	2e-08		G	2.76
chr18:21254837	4e-08		C	2.63
chr6:27151478	4e-08		CA	0.1
chr7:111973156	4e-08		CGCATATATATATATATAT	1.84
rs6044854	2e-07	BFSP1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475823	Verma A	2024	120,335	273,230	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476386	Verma A	2024	105,771	138,105	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476385	Verma A	2024	78,269	165,607	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90078824	Backman JD	2021	75,649	79,475	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082810	Backman JD	2021	75,649	79,475	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90479440	Verma A	2024	56,761	187,115	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90078823	Backman JD	2021	52,659	102,465	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082809	Backman JD	2021	52,659	102,465	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90078598	Backman JD	2021	47,737	91,682	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082584	Backman JD	2021	47,737	91,682	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	0
Tier 4: intronic/intergenic	15

MAF distribution

Bucket	Variants
common (>=0.05)	10
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
unknown	12
intron_variant	3
missense_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs113851554	2	66523432	G>A,T	0.051	intron_variant	MEIS1	2e-65	Tier 4: intronic/intergenic
rs13219518	6	38480094	A>C,G,T	0.28	intron_variant	BTBD9	2e-17	Tier 4: intronic/intergenic
chr1:107187880				0.406			5e-15	Tier 4: intronic/intergenic
chr17:44408004				0.176			2e-12	Tier 4: intronic/intergenic
chr9:140262424				0.119			3e-12	Tier 4: intronic/intergenic
chr11:27653220				0.279			1e-11	Tier 4: intronic/intergenic
rs13107325	4	102267552	C>A,T	0.083	missense_variant	SLC39A8	3e-11	Tier 1: coding
rs429358	19	44908684	T>C	0.137	missense_variant	APOE	4e-11	Tier 1: coding
rs13234969	7	12237812	T>A,C,G	0.408	3_prime_UTR_variant	TMEM106B	4e-11	Tier 2: splice/UTR
chr4:105124090							4e-09	Tier 4: intronic/intergenic
chr2:61223281							1e-08	Tier 4: intronic/intergenic
chr3:132764586							1e-08	Tier 4: intronic/intergenic
chr18:15384806							2e-08	Tier 4: intronic/intergenic
chr9:30687207							2e-08	Tier 4: intronic/intergenic
chr18:21254837							4e-08	Tier 4: intronic/intergenic
chr6:27151478							4e-08	Tier 4: intronic/intergenic
chr7:111973156							4e-08	Tier 4: intronic/intergenic
rs6044854	20	17506587	A>C	0.05	intron_variant	BFSP1	2e-07	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, 20 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Armodafinil	Approved (phase 4)
Acetylcarnitine	Phase 3 (in late-stage trials)
Brexpiprazole	Phase 3 (in late-stage trials)
Brotizolam	Phase 3 (in late-stage trials)
Choline Bitartrate	Phase 3 (in late-stage trials)
Cocoa	Phase 3 (in late-stage trials)
Eplivanserin	Phase 3 (in late-stage trials)
Estazolam	Phase 3 (in late-stage trials)
Ginkgo	Phase 3 (in late-stage trials)
Glutamic Acid	Phase 3 (in late-stage trials)
Lemborexant	Phase 3 (in late-stage trials)
Lormetazepam	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Modafinil	Phase 3 (in late-stage trials)
Nitrazepam	Phase 3 (in late-stage trials)
Oxitriptan	Phase 3 (in late-stage trials)
Ramelteon	Phase 3 (in late-stage trials)
Trazodone	Phase 3 (in late-stage trials)
Volinanserin	Phase 3 (in late-stage trials)
Zolpidem	Phase 3 (in late-stage trials)
Zopiclone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabidiol, Casopitant, Doxepin, Gabapentin, Sesame Oil, Suvorexant, Zaleplon.

Clinical trials & evidence

Clinical trials

Clinical trials: 666.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	584
PHASE4	26
PHASE2	25
PHASE3	9
PHASE1	8
PHASE2/PHASE3	6
EARLY_PHASE1	5
PHASE1/PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04641819	PHASE4	ACTIVE_NOT_RECRUITING	Yangzheng Compound Mixture in the Treatment of Sleep Disorder in Cancer Patients
NCT05042258	PHASE4	RECRUITING	Using Dupilumab to Improve Circadian Function, Sleep and Pruritus in Children With Moderate/Severe Atopic Dermatitis
NCT06480539	PHASE4	RECRUITING	The Effect of Nocturnal Dexmedetomidine on Postoperative Sleep Quality and Fatigue After Major Surgery in Elderly Patients: DEXSLEEP Study
NCT06859892	PHASE4	RECRUITING	Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery
NCT07407400	PHASE4	NOT_YET_RECRUITING	Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients
NCT00359216	PHASE4	COMPLETED	The Effects of Mometasone Furoate Nasal Spray in Subjects With Sleep-disordered Breathing (SDB) Associated With Perennial Allergic Rhinitis (Study P04726)
NCT00822679	PHASE4	COMPLETED	Eszopiclone and Inflammatory Mediators in Patients With Acute Coronary Syndrome
NCT01033565	PHASE4	TERMINATED	Melatonin CR for the Treatment of Impaired Sleep Maintenance in 4-8 Year Old Children With Autism Spectrum Disorders
NCT01164592	PHASE4	COMPLETED	Substudy on the Mechanistic Plausibility of the Clinical Benefits of Adaptive Servo-ventilation
NCT01442610	PHASE4	COMPLETED	Effects of Rasagiline on Sleep Disturbances in Parkinson’s Disease
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02277886	PHASE4	UNKNOWN	Esomeprazole Plus Alginate vs. Esomeprazole Alone for Treatment of Nighttime Reflux Symptom and Sleep Disturbances
NCT03307005	PHASE4	COMPLETED	Improving Sleep Quality in Heart Failure
NCT03317912	PHASE4	UNKNOWN	Perioperative Lignocaine and Sleep Disturbance
NCT03522207	PHASE4	TERMINATED	Accuracy and Efficacy of Trazodone (Desyrel) on Sleep Quality and Pain Management of TMD Patient
NCT03818581	PHASE4	COMPLETED	Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes
NCT04188106	PHASE4	COMPLETED	Efficacy and Tolerability of Combination Varenicline With Hydroxyzine as a Potential Smoking Cessation Treatment
NCT04318067	PHASE4	UNKNOWN	Melatonin in ADHD and Sleep Problems
NCT04528173	PHASE4	TERMINATED	Opioid-Free Anesthetic for Tonsillectomy
NCT04610827	PHASE4	TERMINATED	Oral Iron Frequency for Childhood Restless Leg Syndrome/Periodic Limb Movement Disorder
NCT04693533	PHASE4	TERMINATED	Fremanezumab, Migraine and Sleep
NCT04706091	PHASE4	COMPLETED	Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia
NCT05325762	PHASE4	UNKNOWN	Effect of Propofol on Postoperative Sleep Quality in Elderly Patients With Sleep Disorders
NCT05950932	PHASE4	UNKNOWN	Effects of Melissa Extract on Sleep Characteristics
NCT06117969	PHASE4	UNKNOWN	the Effects of Different Therapy Regimens on Menopausal Sleep Disorders
NCT06898463	PHASE4	COMPLETED	Comparison Of The Effects Of Melatonin Premedication And Ketamine On Postoperative Sleep Quality İn Rhinoplasty
NCT05625360	PHASE3	RECRUITING	REmotely-delivered Supportive Programs for Improving Surgical Pain and disTrEss
NCT07538284	PHASE2/PHASE3	NOT_YET_RECRUITING	MInimizing Delirium With Nasal Dexmedetomidine-InducEd Sleep (MIDDIES)
NCT01429636	PHASE3	COMPLETED	Applied Relaxation (AR) Technique Versus Its Modified Version for Treating Menopausal Symptoms
NCT01468038	PHASE3	COMPLETED	A Double-blind Placebo Controlled Trial of Sentra PM, a Medical Food
NCT01907711	PHASE2/PHASE3	UNKNOWN	Clinical Trial to Evaluate the Effectiveness of Acupuncture as a Treatment in Patients Diagnosed With CFS.
NCT01922999	PHASE2/PHASE3	UNKNOWN	Different Doses of Oral Melatonin Supplements in Chronic Kidney Disease (CKD)-Associated Sleep Disorders
NCT01942733	PHASE3	COMPLETED	Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder
NCT03412591	PHASE2/PHASE3	COMPLETED	The Efficacy of Suvorexant in Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT04451668	PHASE3	COMPLETED	An Open Label Study of FT218 in Subjects With Narcolepsy
NCT04603781	PHASE2/PHASE3	SUSPENDED	CBD Oil for Reducing Emotional Impact of COVID-19
NCT04759703	PHASE2/PHASE3	TERMINATED	Treatment of Restless Legs Symptoms With Pramipexole to Improve the Outcomes of Protracted Opioid Withdrawal in OUD
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT06281561	PHASE3	UNKNOWN	Dexmedetomidine Premedication for Post-anaesthesia Sleep Disturbance

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MELATONIN	4	15
ZOLPIDEM	4	12
SUVOREXANT	4	4
HYDROXYZINE	4	3
SOLRIAMFETOL	4	3
TRAZODONE	4	3
ESZOPICLONE	4	2
KETOROLAC	4	2
VARENICLINE	4	2
ZOPICLONE	4	2
BREXPIPRAZOLE	4	1
DUPILUMAB	4	1
ESOMEPRAZOLE	4	1
FERROUS SULFATE	4	1
ISTRADEFYLLINE	4	1
LEMBOREXANT	4	1
METHYLPHENIDATE HYDROCHLORIDE	4	1
MODAFINIL	4	1
PRAMIPEXOLE	4	1
RAMELTEON	4	1
RASAGILINE	4	1
TESAMORELIN	4	1
TIBOLONE	4	1
UPADACITINIB	4	1
LAVENDER OIL	3	2
BENZODIAZEPINE	3	1
DEXPRAMIPEXOLE	3	1
MICROCRYSTALLINE CELLULOSE	3	1
PALMIDROL	3	1
PSILOCYBIN	3	1