Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.039
- Threshold uncertainty score
- 0.538
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
- Teacher spread
- 0.245 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. RESULTS: ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Biological Psychiatry
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- not available
- Funders
- Janssen BiotechNational Institute on Drug AbuseNational Institute of Mental HealthStrategic Research CouncilNational Health and Medical Research CouncilAustralian Research CouncilRoy J. and Lucille A. Carver College of Medicine, University of IowaBiotechnology and Biological Sciences Research CouncilStanley Center for Psychiatric Research, Broad InstituteUniversity of North Carolina at Chapel HillDirectorate for Biological SciencesNational Institutes of HealthH. Lundbeck A/SMedical Research CouncilServierRheinische Friedrich-Wilhelms-Universität BonnMedical Research Council CanadaCentre Hospitalier Universitaire VaudoisGöteborgs UniversitetVetenskapsrådetNational Cancer InstituteLundbeckfondenDeutsche ForschungsgemeinschaftNederlandse Organisatie voor Wetenschappelijk OnderzoekQueensland Brain InstituteKarolinska InstitutetUniversity of QueenslandQueensland University of TechnologySchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversity of GlasgowUniversity of New EnglandMassachusetts Institute of TechnologyEuropean Science FoundationKing's College LondonChief Scientist OfficeNational Institute of Diabetes and Digestive and Kidney DiseasesInstitut for Klinisk Medicin, Aarhus UniversitetKing’s College LondonScottish Funding CouncilSanofiBroad InstituteWellcome TrustVirginia Commonwealth UniversityNational Institute on Alcohol Abuse and AlcoholismCentre for Cognitive Ageing and Cognitive EpidemiologyUniversity of PittsburghQIMR Berghofer Medical Research InstituteScottish GovernmentMinistry of Cultural AffairsPhilipps-Universität MarburgUniversity of Texas Southwestern Medical CenterCardiff UniversityCentro de Investigación Biomédica en Red de Salud MentalEli Lilly and CompanySeventh Framework ProgrammeKaiser PermanenteVrije Universiteit AmsterdamStiftelsen för Strategisk ForskningUniversity of DundeeEuropean CommissionUniversity of AberdeenUniversidad del AtlánticoMassachusetts General HospitalNational Science FoundationWellcomeAarhus UniversitetZonMwStrategiske ForskningsrådGlaxoSmithKlineNational Institute for Health and Care ResearchUniversidad de GranadaAarhus UniversitetshospitalNational Center for Research ResourcesNational Alliance for Research on Schizophrenia and DepressionMenzies Centre for Australian Studies, King's College London, University of LondonFlorida Atlantic UniversityChief Scientist Office, Scottish Government Health and Social Care DirectorateInstitute of Psychiatry, Psychology and Neuroscience, King’s College LondonHáskóli ÍslandsLandspítali HáskólasjúkrahúsBundesministerium für Bildung und ForschungInstitute of GeneticsUniversität GreifswaldNational Rosacea SocietyChinese Society of Clinical OncologyAmgenPfizer
- Keywords
- Depression (economics)GenomicsGenome-wide association studyPsychiatryPsychiatric geneticsMajor depressive disorderAssociation (psychology)PsychologyMedicineClinical psychologyGenomeGeneticsBiologyGenotypeSchizophrenia (object-oriented programming)GeneSingle-nucleotide polymorphismPsychotherapist
- Has abstract in OpenAlex
- yes