Headache disorder
diseaseOn this page
Also known as cephalgia syndromecephalgia syndromeschronic daily headachechronic daily headacheschronic headachechronic headachesdaily headache, chronicdaily headaches, chronicheadache syndromeheadache syndromesheadache, chronicheadache, chronic dailyheadache, intractableheadaches, chronicheadaches, chronic dailyheadaches, intractableintractable headacheintractable headachessyndrome, headache
Summary
Headache disorder (MONDO:0021146) is a disease with 9 GWAS associations across 25 studies and 120 clinical trials. Top therapeutic interventions include amitriptyline, sumatriptan, and bimatoprost. A subtype of neurological pain disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 9
- Clinical trials: 120
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | headache disorder |
| Mondo ID | MONDO:0021146 |
| EFO | EFO:0009550 |
| MeSH | D020773 |
| SNOMED CT | 230461009 |
| UMLS | C0393735 |
| MedGen | 140743 |
| Is cancer (heuristic) | no |
Also known as: cephalgia syndrome · cephalgia syndromes · chronic daily headache · chronic daily headaches · chronic headache · chronic headaches · daily headache, chronic · daily headaches, chronic · headache disorder · headache syndrome · headache syndromes · headache, chronic · headache, chronic daily · headache, intractable · headaches, chronic · headaches, chronic daily · headaches, intractable · intractable headache · intractable headaches · syndrome, headache
Data availability: 9 GWAS associations (25 studies).
Disease family
This is a subtype of neurological pain 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 › neurological pain disorder › headache disorder
Related subtypes (8): psychologic dyspareunia, paroxysmal extreme pain disorder, neuralgia, vulvodynia, coccygodynia, Eagle syndrome, chronic pain syndrome, glossodynia
Subtypes (4): hypnic headache, reversible cerebral vasoconstriction syndrome, spontaneous intracranial hypotension, exertional headache
Genetics & variants
GWAS landscape
9 GWAS associations across 25 studies. Top hits map to 1 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| chr9:127484794 | 8e-09 | C | 1.79 | |
| chr14:74044623 | 2e-08 | A | 3.29 | |
| chr13:112699017 | 3e-08 | T | 2.9 | |
| chr6:63019367 | 3e-08 | T | 2.49 | |
| chr10:89223757 | 4e-08 | G | 2.07 | |
| chr14:90673265 | 4e-08 | G | 3.21 | |
| chr2:76217550 | 4e-08 | G | 0.1 | |
| chr6:72122371 | 4e-08 | AT | 2.66 | |
| rs11100926 | 5e-08 | SLC10A7 | ? |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90477537 | Verma A | 2024 | 62,207 | 344,126 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90129443 | Zorina-Lichtenwalter K | 2023 | 40,222 | 345,292 | Genetic risk shared across 24 chronic pain conditions: identification and characterization with genomic structural equation modeling. |
| GCST90476954 | Verma A | 2024 | 31,933 | 283,735 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90477536 | Verma A | 2024 | 26,073 | 79,119 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90481055 | Verma A | 2024 | 26,073 | 79,119 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90476957 | Verma A | 2024 | 14,106 | 301,562 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90477534 | Verma A | 2024 | 11,822 | 40,589 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90435919 | Zhou W | 2018 | 7,891 | 398,780 | Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. |
| GCST90476953 | Verma A | 2024 | 6,226 | 49,279 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90481214 | Verma A | 2024 | 6,226 | 49,279 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 9 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 1 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 8 |
Functional consequences
| Consequence | Count |
|---|---|
| unknown | 8 |
| intron_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| chr9:127484794 | 8e-09 | Tier 4: intronic/intergenic | ||||||
| chr14:74044623 | 2e-08 | Tier 4: intronic/intergenic | ||||||
| chr13:112699017 | 3e-08 | Tier 4: intronic/intergenic | ||||||
| chr6:63019367 | 3e-08 | Tier 4: intronic/intergenic | ||||||
| chr10:89223757 | 4e-08 | Tier 4: intronic/intergenic | ||||||
| chr14:90673265 | 4e-08 | Tier 4: intronic/intergenic | ||||||
| chr2:76217550 | 4e-08 | Tier 4: intronic/intergenic | ||||||
| chr6:72122371 | 4e-08 | Tier 4: intronic/intergenic | ||||||
| rs11100926 | 4 | 146491251 | G>A,C,T | 0.05 | intron_variant | SLC10A7 | 5e-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
No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Onabotulinumtoxina, Sodium Chloride.
Clinical trials & evidence
Clinical trials
Clinical trials: 120.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 102 |
| PHASE1/PHASE2 | 5 |
| PHASE3 | 4 |
| PHASE4 | 3 |
| PHASE2 | 3 |
| PHASE1 | 2 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00449787 | PHASE4 | COMPLETED | Comparing Naproxen to Sumatriptan for Emergency Headache Patients |
| NCT02090998 | PHASE4 | TERMINATED | Sphenopalatine Ganglion Nerve Block vs. Elavil for Treatment of Transformed Migraines |
| NCT04050293 | PHASE4 | TERMINATED | Therapy for Migraine Prevention in Children 6-11 Years of Age |
| NCT04151472 | PHASE3 | RECRUITING | Idebenone for the Preventive Treatment of Migraine |
| NCT05306899 | PHASE3 | RECRUITING | Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches |
| NCT00269581 | PHASE3 | COMPLETED | Headstrong Intervention for Pediatric Headache |
| NCT00457496 | PHASE3 | COMPLETED | Effectiveness of a Cognitive and Physical Intervention to Reduce Head and Muscle Pain in Working Communities |
| NCT00205829 | PHASE1/PHASE2 | COMPLETED | Bion for Occipital Nerve Stimulation |
| NCT00205894 | PHASE1/PHASE2 | COMPLETED | Occipital Nerve Stimulation to Treat Chronic Headaches |
| NCT00228267 | PHASE2 | COMPLETED | Propofol Injection for Daily Headache |
| NCT00246350 | PHASE2 | COMPLETED | Spinal Manipulation for Treatment of Chronic Headaches |
| NCT02624661 | PHASE1/PHASE2 | TERMINATED | Glycerol Block of the Trigeminal Ganglion in Trigeminal Neuralgia Using a New Neuronavigation-based Surgical Technique |
| NCT02662972 | PHASE1/PHASE2 | COMPLETED | Botulinum Toxin Type A Block of the Sphenopalatine Ganglion in Trigeminal Neuralgia. Safety Issues. |
| NCT03419715 | PHASE2 | UNKNOWN | Topical Bimatoprost in the Treatment of Migraine |
| NCT03691272 | PHASE1/PHASE2 | COMPLETED | rTMS Treatment of Persistent Headache and Post Concussion Symptoms Attributed to Mild Traumatic Injury to the Head |
| NCT00181064 | PHASE1 | COMPLETED | Atkins Diet for Difficult-to-Control Headaches in Teenagers |
| NCT01767428 | PHASE1 | COMPLETED | Pharmacokinetic Study to Compare Two Formulations of Paracetamol |
| NCT03346252 | EARLY_PHASE1 | COMPLETED | The Effect of Botulinum Toxin A on Headache Attributed to TMD |
| NCT03231241 | Not specified | RECRUITING | Analysis of Headache Chronification With Imaging, Deep Phenotyping, and Proteomics |
| NCT03416114 | Not specified | RECRUITING | RegistRare: a Retro-prospective Registry of Rare Primary Headaches in Italian Tertiary Headache Centres |
| NCT04715685 | Not specified | RECRUITING | Mind Body Balance for Pediatric Migraine |
| NCT04936321 | Not specified | ACTIVE_NOT_RECRUITING | Intervention for Sleep and Pain in Youth: a Randomized Controlled Trial |
| NCT05415020 | Not specified | RECRUITING | Determining the Utility of a Behavioral Intervention in Chronic Migraine |
| NCT05754190 | Not specified | RECRUITING | Assessing Symptom and Mood Dynamics in Pain Using the Smartphone Application SOMA |
| NCT05889624 | Not specified | RECRUITING | Responding With Evidence and Access for Childhood Headaches |
| NCT06041997 | Not specified | RECRUITING | Smartphone Use Restriction as Treatment of Primary Headache |
| NCT06077747 | Not specified | RECRUITING | Lumbar Vein Embolization for Chronic Headaches With Nutcracker Physiology |
| NCT06546462 | Not specified | NOT_YET_RECRUITING | Can a Specific OMT Protocol Influence Patient Pain and Associated Analgesia Use for Primary Headache Disorders? |
| NCT06646081 | Not specified | NOT_YET_RECRUITING | The Impact of Greater Occipital Nerve and Stellate Ganglion Block Treatments on Sleep in Chronic Headache Management |
| NCT06716489 | Not specified | RECRUITING | Aerobic Exercise and Its Impact on Sensory, Musculoskeletal, and Psychosocial Aspects in Migraine |
| NCT06868251 | Not specified | NOT_YET_RECRUITING | Prevalence and Pattern of Headache in Pediatric Epilepsy |
| NCT06921109 | Not specified | RECRUITING | Assessment of the Effectiveness of Virtual Reality as a Learning Tool for Relaxation Techniques in Reducing Pediatric Migraines and Tension Type Headache |
| NCT07033520 | Not specified | NOT_YET_RECRUITING | Effects of Online Mindfulness Therapy on Pain and Stress in Adults With Chronic Migraine and Adverse Childhood Experiences |
| NCT07071506 | Not specified | RECRUITING | New Methods for Evaluating Preventive Migraine Treatment |
| NCT07268768 | Not specified | RECRUITING | PERSONOLOGICAL STRUCTURE, COGNITIVE FUNCTIONS AND CENTRAL SENSITIZATION IN HEADACHE |
| NCT07307508 | Not specified | RECRUITING | Efficacy of Scalp Block in Managing Post Subarachnoid Hemorrhage Headache in Critically Ill Patients. A Single Centre Randomized Controlled Trial |
| NCT07340775 | Not specified | NOT_YET_RECRUITING | Hypersensitivity to Amylin in Post-Traumatic Headache |
| NCT07340788 | Not specified | NOT_YET_RECRUITING | Amylin-Induced Migraine Attacks Without Aura |
| NCT07419607 | Not specified | RECRUITING | MIGRAFIT: Evaluating a Group Therapy Program Combining Physical Activity, Progressive Muscle Relaxation and Psychoeducation for Adolescents With Migraine |
| NCT00086021 | Not specified | COMPLETED | Acupuncture for the Treatment of Chronic Daily Headaches |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| AMITRIPTYLINE | 4 | 6 |
| SUMATRIPTAN | 4 | 3 |
| BIMATOPROST | 4 | 1 |
| GLYCERIN | 4 | 1 |
| IDEBENONE | 4 | 1 |
| NAPROXEN | 4 | 1 |
| CARBON MONOXIDE | 3 | 1 |
| ZUCAPSAICIN | 3 | 1 |
| AMLINTIDE | 2 | 2 |
| AMYLIN | 0 | 2 |
| CHEMBL1618254 | 0 | 1 |
| CHEMBL4303730 | 0 | 1 |