GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT 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.
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
- Meta-epidemiology (narrow)
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Meta-analysisConsensus signal: none
- Genre
- Candidate signal: ReviewConsensus signal: Review
- Teacher disagreement score
- 0.559
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| 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
- 0.273 · 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
Abstract The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level ( P <5 × 10 −8 ). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.
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
- Molecular Psychiatry
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of TorontoCentre for Addiction and Mental Health
- Funders
- National Center for Research ResourcesNational Institute of Dental and Craniofacial ResearchNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteBiotechnology and Biological Sciences Research CouncilEllison Medical FoundationDirectorate for Biological SciencesNational Institutes of HealthNational Institute on AgingCentre for Cognitive Ageing and Cognitive EpidemiologyAcademy of FinlandUniversity of EdinburghUniversitetet i BergenSamfundet FolkhälsanBergens ForskningsstiftelseNational Center for Advancing Translational SciencesSigne ja Ane Gyllenbergin SäätiöMedical Research CouncilEmil Aaltosen SäätiöNational Institute on Drug AbuseNovo NordiskNorges ForskningsrådCanadian Institutes of Health ResearchScience Foundation IrelandNational Science FoundationCentre for Addiction and Mental Health FoundationFinska LäkaresällskapetHelse VestHelsingin YliopistoFolkhälsanin Tutkimussäätiö
- Keywords
- Genome-wide association studyMinor allele frequencySingle-nucleotide polymorphismGeneticsGenetic associationBiologyPsychologyGenotypeGene
- Has abstract in OpenAlex
- yes