Generalized anxiety disorder
diseaseOn this page
Also known as GAD
Summary
Generalized anxiety disorder (MONDO:0001942) is a disease with 64 GWAS associations across 17 studies and 354 clinical trials. Top therapeutic interventions include quetiapine, escitalopram, and paroxetine. A subtype of anxiety disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 64
- Clinical trials: 354
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | generalized anxiety disorder |
| Mondo ID | MONDO:0001942 |
| EFO | EFO:1001892 |
| DOID | DOID:14320 |
| ICD-10-CM | F41.1 |
| NCIT | C92622 |
| SNOMED CT | 21897009 |
| UMLS | C0270549 |
| MedGen | 452363 |
| Is cancer (heuristic) | no |
Also known as: GAD
Data availability: 64 GWAS associations (17 studies) · 11 cell lines.
Disease family
This is a subtype of anxiety 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 › mental disorder › anxiety disorder › generalized anxiety disorder
Related subtypes (9): separation anxiety disorder, neurocirculatory asthenia, phobic disorder, acute stress disorder, neurotic disorder, panic disorder, obsessive-compulsive disorder, anxiety, mixed anxiety and depressive disorder
Genetics & variants
GWAS landscape
64 GWAS associations across 17 studies. Top hits map to 33 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs62056789 | 4e-13 | MAPT, MAPT-IT1 | A | 0.02 |
| rs55770986 | 6e-11 | MAD1L1 | T | 0.02 |
| rs12699336 | 1e-10 | TMEM106B - VWDE | A | 0.01 |
| rs9969125 | 3e-10 | MAD1L1 | T | 0.02 |
| rs146434301 | 3e-10 | AQP4-AS1, CHST9 | ? | |
| rs9827285 | 4e-10 | SATB1-AS1 | A | 0.01 |
| rs12134194 | 1e-09 | LINC02796 - KRT8P21 | T | 0.01 |
| rs148579586 | 1e-09 | SERPINB8 - LINC01924 | ? | 0.1 |
| rs111606492 | 1e-09 | LILRA1 | ? | |
| rs7665476 | 3e-09 | HS3ST1 - LINC02360 | T | 0.01 |
| rs184992408 | 3e-09 | LINC01478 | ? | |
| rs201074060 | 4e-09 | LINC01924 | ? | 0.1 |
| rs4645151 | 5e-09 | SATB1-AS1 | T | 0.01 |
| rs4906947 | 6e-09 | SNHG14 | C | 0.01 |
| rs1385219 | 6e-09 | ADH5P4 - NUFIP1P1 | T | 0.01 |
| rs931774 | 7e-09 | SOX6 | T | 0.02 |
| rs72766883 | 7e-09 | LAMC3 | A | 0.03 |
| rs78286508 | 7e-09 | RNA5SP225 - MTCO2P31 | ? | |
| rs12376738 | 9e-09 | FAM120A | T | 0.01 |
| rs4233093 | 1e-08 | LINC02796 - KRT8P21 | A | 0.01 |
| rs114830993 | 2e-08 | PRICKLE2 | ? | |
| rs73034263 | 2e-08 | IGSF9B | C | 0.01 |
| rs1821257 | 2e-08 | CTNNA1 | T | 0.02 |
| rs147176127 | 2e-08 | DTNA | ? | |
| rs11162571 | 4e-08 | LHX8 | T | 0.02 |
| rs9897957 | 4e-08 | KPNB1-DT | T | 0.01 |
| rs45510091 | 4e-08 | BLTP1 | A | 0.02 |
| rs712407 | 5e-08 | LRFN5 | A | 0.01 |
| rs147997219 | 1e-07 | LMTK3 | ? | |
| rs74938865 | 1e-07 | BETALINC1 - LINC01727 | ? |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90481767 | Verma A | 2024 | 33,499 | 400,765 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90078639 | Backman JD | 2021 | 19,743 | 24,570 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90082625 | Backman JD | 2021 | 19,743 | 24,570 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90481766 | Verma A | 2024 | 7,498 | 109,040 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90481764 | Verma A | 2024 | 5,280 | 51,553 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90079809 | Backman JD | 2021 | 2,967 | 378,840 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90083795 | Backman JD | 2021 | 2,967 | 378,840 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90651876 | Liu TY | 2025 | 1,367 | 143,233 | Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population. |
| GCST90481765 | Verma A | 2024 | 397 | 6,221 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90435865 | Zhou W | 2018 | 150 | 365,476 | Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. |
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 | 50 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 38 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 12 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 32 |
| intergenic_variant | 16 |
| non_coding_transcript_exon_variant | 1 |
| unknown | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs62056789 | 17 | 45898049 | A>C,T | 0.05 | non_coding_transcript_exon_variant | MAPT, MAPT-IT1 | 4e-13 | Tier 4: intronic/intergenic |
| rs55770986 | 7 | 2048188 | T>C | 0.05 | intron_variant | MAD1L1 | 6e-11 | Tier 4: intronic/intergenic |
| rs12699336 | 7 | 12243624 | T>A | 0.05 | intergenic_variant | TMEM106B - VWDE | 1e-10 | Tier 4: intronic/intergenic |
| rs9969125 | 7 | 2048825 | C>A,T | 0.05 | intron_variant | MAD1L1 | 3e-10 | Tier 4: intronic/intergenic |
| rs146434301 | 18 | 27143535 | T>TA | 0.05 | intron_variant | AQP4-AS1, CHST9 | 3e-10 | Tier 4: intronic/intergenic |
| rs9827285 | 3 | 18754026 | G>A | 0.05 | intron_variant | SATB1-AS1 | 4e-10 | Tier 4: intronic/intergenic |
| rs12134194 | 1 | 73072668 | T>A,G | 0.05 | intergenic_variant | LINC02796 - KRT8P21 | 1e-09 | Tier 4: intronic/intergenic |
| rs148579586 | 18 | 64025735 | C>A | 0.05 | intergenic_variant | SERPINB8 - LINC01924 | 1e-09 | Tier 4: intronic/intergenic |
| rs111606492 | 19 | 54594504 | C>A,T | 0.05 | intron_variant | LILRA1 | 1e-09 | Tier 4: intronic/intergenic |
| rs7665476 | 4 | 11576733 | C>A,G,T | 0.05 | intergenic_variant | HS3ST1 - LINC02360 | 3e-09 | Tier 4: intronic/intergenic |
| rs184992408 | 18 | 44289079 | T>C,G | 0.05 | intron_variant | LINC01478 | 3e-09 | Tier 4: intronic/intergenic |
| rs201074060 | 18 | 64052114 | T>TA | 0.05 | intergenic_variant | LINC01924 | 4e-09 | Tier 4: intronic/intergenic |
| rs4645151 | 3 | 18688941 | C>A,G,T | 0.05 | intron_variant | SATB1-AS1 | 5e-09 | Tier 4: intronic/intergenic |
| rs4906947 | 15 | 25142039 | C>A,G | 0.05 | intergenic_variant | SNHG14 | 6e-09 | Tier 4: intronic/intergenic |
| rs1385219 | 6 | 66044583 | C>T | 0.05 | intron_variant | ADH5P4 - NUFIP1P1 | 6e-09 | Tier 4: intronic/intergenic |
| rs931774 | 11 | 16319103 | T>C | 0.05 | intron_variant | SOX6 | 7e-09 | Tier 4: intronic/intergenic |
| rs72766883 | 9 | 131027334 | G>A,T | 0.05 | intron_variant | LAMC3 | 7e-09 | Tier 4: intronic/intergenic |
| rs78286508 | 6 | 153481717 | T>G | 0.05 | intergenic_variant | RNA5SP225 - MTCO2P31 | 7e-09 | Tier 4: intronic/intergenic |
| rs12376738 | 9 | 93539518 | T>A,C,G | 0.05 | intron_variant | FAM120A | 9e-09 | Tier 4: intronic/intergenic |
| rs4233093 | 1 | 72980562 | G>A | 0.05 | intergenic_variant | LINC02796 - KRT8P21 | 1e-08 | Tier 4: intronic/intergenic |
| rs114830993 | 3 | 64294679 | T>C | intron_variant | PRICKLE2 | 2e-08 | Tier 4: intronic/intergenic | |
| rs73034263 | 11 | 133938143 | C>A,G | 0.05 | intron_variant | IGSF9B | 2e-08 | Tier 4: intronic/intergenic |
| rs1821257 | 5 | 138612735 | T>C | 0.05 | intergenic_variant | CTNNA1 | 2e-08 | Tier 4: intronic/intergenic |
| rs147176127 | 18 | 34540044 | G>C,T | 0.05 | intron_variant | DTNA | 2e-08 | Tier 4: intronic/intergenic |
| rs11162571 | 1 | 75129466 | C>T | 0.05 | intron_variant | LHX8 | 4e-08 | Tier 4: intronic/intergenic |
| rs9897957 | 17 | 47631983 | T>C,G | 0.05 | intron_variant | KPNB1-DT | 4e-08 | Tier 4: intronic/intergenic |
| rs45510091 | 4 | 122265238 | A>G | 0.05 | intron_variant | BLTP1 | 4e-08 | Tier 4: intronic/intergenic |
| rs712407 | 14 | 41648171 | C>A,T | 0.05 | intron_variant | LRFN5 | 5e-08 | Tier 4: intronic/intergenic |
| rs147997219 | 19 | 48501660 | C>G,T | 0.05 | intron_variant | LMTK3 | 1e-07 | Tier 4: intronic/intergenic |
| rs74938865 | 20 | 21536834 | T>G | 0.05 | intergenic_variant | BETALINC1 - LINC01727 | 1e-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
2 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Alprazolam | Approved (phase 4) |
| Pregabalin | Approved (phase 4) |
| Buspirone | Phase 3 (in late-stage trials) |
| Chamomile | Phase 3 (in late-stage trials) |
| Duloxetine | Phase 3 (in late-stage trials) |
| Escitalopram | Phase 3 (in late-stage trials) |
| Fluvoxamine | Phase 3 (in late-stage trials) |
| Imagabalin | Phase 3 (in late-stage trials) |
| Paroxetine | Phase 3 (in late-stage trials) |
| Sertraline | Phase 3 (in late-stage trials) |
| Troriluzole | Phase 3 (in late-stage trials) |
| Vilazodone | Phase 3 (in late-stage trials) |
| Vortioxetine | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cariprazine, Eszopiclone, Glutamine, Pexacerfont, Ulotaront.
Clinical trials & evidence
Clinical trials
Clinical trials: 354.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 230 |
| PHASE3 | 42 |
| PHASE4 | 33 |
| PHASE2 | 30 |
| PHASE1 | 10 |
| PHASE2/PHASE3 | 4 |
| PHASE1/PHASE2 | 4 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04751864 | PHASE4 | ACTIVE_NOT_RECRUITING | Brain Stimulation & Generalized Anxiety Study |
| NCT06218030 | PHASE4 | RECRUITING | Adjunctive Treatment With L-methylfolate for Treatment-Resistant Generalized Anxiety Disorder: a Pilot Study |
| NCT00044642 | PHASE4 | COMPLETED | Lorazepam-Induced Toxicity in the Aged |
| NCT00105586 | PHASE4 | COMPLETED | Drug Therapy for Generalized Anxiety Disorder Among the Elderly |
| NCT00120458 | PHASE4 | COMPLETED | Black Cohosh as Alternative Therapy for Treating Menopause-Related Anxiety |
| NCT00167479 | PHASE4 | COMPLETED | A Study of Risperidone Monotherapy in Bipolar Anxiety |
| NCT00219349 | PHASE4 | COMPLETED | Cognitive-Behavioral Therapy and Escitalopram for Generalized Anxiety Disorder(GAD) |
| NCT00235508 | PHASE4 | COMPLETED | Safety and Efficacy of Eszopiclone in Patients With Generalized Anxiety Disorder |
| NCT00266409 | PHASE4 | COMPLETED | Trial to Compare Time to Response in the Symptoms of Anxiety to Concomitant Treatment With Niravam™ and an SSRI or SNRI to Treatment With an SSRI or SNRI Alone in Subjects With Generalized Anxiety Disorder or Panic Disorder |
| NCT00330174 | PHASE4 | COMPLETED | Acamprosate in Alcoholics With Comorbid Anxiety or Depression |
| NCT00347269 | PHASE4 | COMPLETED | Primary Care Intervention Strategy for Anxiety Disorders |
| NCT00352469 | PHASE4 | COMPLETED | Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety |
| NCT00374543 | PHASE4 | TERMINATED | Ziprasidone for the Treatment of Generalized Anxiety in Patients With Bipolar Disorder |
| NCT00438386 | PHASE4 | COMPLETED | Aripiprazole for the Treatment of Refractory Anxiety |
| NCT00539357 | PHASE4 | COMPLETED | A Pilot Study of Cranial Electrotherapy Stimulation[CES] for Generalized Anxiety Disorder |
| NCT00579280 | PHASE4 | COMPLETED | Quetiapine SR and Divalproex Sodium ER in the Treatment of Anxiety in Bipolar Disorder With Panic Disorder and/or GAD |
| NCT00624780 | PHASE4 | COMPLETED | Safety and Efficacy Evaluation Of Pregabalin (Lyrica) With Patients With Generalized Anxiety Disorder |
| NCT00645983 | PHASE4 | COMPLETED | Chamomile Therapy for Generalized Anxiety |
| NCT00662259 | PHASE4 | COMPLETED | Drug Treatment Validation of Functional Magnetic Resonance Imaging in Generalized Anxiety Disorder |
| NCT00668265 | PHASE4 | TERMINATED | Anxiety in Recovering Opiate Dependence |
| NCT00701675 | PHASE4 | COMPLETED | Pharmacological Treatment of Generalized Anxiety Disorder in the Elderly |
| NCT00902564 | PHASE4 | COMPLETED | Escitalopram in Patients With Generalized Anxiety Disorder |
| NCT00961298 | PHASE4 | COMPLETED | An Open Label Trial of Duloxetine in the Treatment of Irritable Bowel Syndrome and Comorbid Generalized Anxiety Disorder |
| NCT01033851 | PHASE4 | COMPLETED | Stress Reduction Techniques and Anxiety: Therapeutic and Neuroendocrine Effects |
| NCT01118780 | PHASE4 | COMPLETED | A Study of Duloxetine in Elderly Generalized Anxiety Disorder |
| NCT01172652 | PHASE4 | COMPLETED | Ziprasidone in Bipolar Disorder With Comorbid Lifetime Panic or Generalized Anxiety Disorder(GAD) |
| NCT01201967 | PHASE4 | COMPLETED | A Collaborative Care Program to Improve Treatment of Depression and Anxiety Disorders in Cardiac Patients |
| NCT01244711 | PHASE4 | TERMINATED | Open-Label Pilot Study to Examine the Value of Substituting Quetiapine for Benzodiazepines |
| NCT01614041 | PHASE4 | COMPLETED | Tandospirone Citrate in the Treatment of Patients With Generalized Anxiety Disorder |
| NCT01975480 | PHASE4 | COMPLETED | Efficacy of SNRI Treatment on Prefrontality in Patients With GAD and Other Comorbities |
| NCT02219880 | PHASE4 | COMPLETED | Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial |
| NCT03522844 | PHASE4 | COMPLETED | Treatments for Anxiety: Meditation and Escitalopram |
| NCT03785223 | PHASE4 | COMPLETED | A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity |
| NCT05772104 | PHASE3 | RECRUITING | Clinical Trial of Shugan Jieyu Capsule in Generalized Anxiety Disorder |
| NCT06243614 | PHASE3 | RECRUITING | Phase Ⅲ Clinical Trial of Buagafuran Capsules in the Treatment of GAD |
| NCT06243640 | PHASE3 | RECRUITING | Phase 3 Clinical Trial of Buagafuran Capsules in the Treatment of GAD |
| NCT06741228 | PHASE3 | ACTIVE_NOT_RECRUITING | A Phase 3 Trial of MM120 for Generalized Anxiety Disorder (Voyage) |
| NCT06809595 | PHASE3 | ACTIVE_NOT_RECRUITING | A Phase 3 Trial of MM120 for Generalized Anxiety Disorder (Panorama) |
| NCT07123467 | PHASE3 | RECRUITING | Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder |
| NCT00000389 | PHASE3 | COMPLETED | Treatment for Anxiety in Children |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| QUETIAPINE | 4 | 13 |
| ESCITALOPRAM | 4 | 8 |
| PAROXETINE | 4 | 8 |
| FLUVOXAMINE | 4 | 6 |
| VILAZODONE | 4 | 6 |
| ZIPRASIDONE | 4 | 6 |
| VORTIOXETINE | 4 | 5 |
| TIAGABINE | 4 | 4 |
| ALPRAZOLAM | 4 | 3 |
| CARIPRAZINE | 4 | 3 |
| DESVENLAFAXINE | 4 | 3 |
| DULOXETINE | 4 | 3 |
| LORAZEPAM | 4 | 3 |
| ESZOPICLONE | 4 | 2 |
| ZOPICLONE | 4 | 2 |
| ACAMPROSATE | 4 | 1 |
| ADENOSINE PHOSPHATE | 4 | 1 |
| ARIPIPRAZOLE | 4 | 1 |
| CANNABIDIOL | 4 | 1 |
| CIMETIDINE | 4 | 1 |
| DIVALPROEX SODIUM | 4 | 1 |
| ISOPROTERENOL | 4 | 1 |
| LEVOMEFOLIC ACID | 4 | 1 |
| MEMANTINE | 4 | 1 |
| METHYLPHENIDATE | 4 | 1 |
| PREGABALIN | 4 | 1 |
| RISPERIDONE | 4 | 1 |
| SERTRALINE | 4 | 1 |
| IMAGABALIN | 3 | 10 |
| CHAMOMILE | 3 | 1 |
Related Atlas pages
- Drugs: Quetiapine, Escitalopram, Paroxetine, Fluvoxamine, Vilazodone, Ziprasidone, Vortioxetine, Tiagabine, Alprazolam, Cariprazine, Desvenlafaxine, Duloxetine, Lorazepam, Eszopiclone, Zopiclone, Acamprosate, Adenosine Phosphate, Aripiprazole, Cannabidiol, Cimetidine, Divalproex, Isoproterenol, Levomefolic Acid, Memantine, Methylphenidate, Pregabalin, Risperidone, Sertraline, Imagabalin, Chamomile