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Record W2903416893 · doi:10.1038/s41467-018-07340-5

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

2018· review· en· W2903416893 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityUniversity of British ColumbiaMcMaster UniversityPopulation Health Research Institute
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNational Human Genome Research InstituteMedical Research CouncilNational Cancer InstituteUniversitat Autònoma de BarcelonaSchool of Medicine, Emory UniversityNovo Nordisk FondenScience for Life LaboratoryTerveyden ja hyvinvoinnin laitosFondazione I.R.C.C.S. Istituto Neurologico Carlo BestaJohns Hopkins UniversityChildren's National HospitalUppsala UniversitetNational Institute on Minority Health and Health DisparitiesDeutsche ForschungsgemeinschaftBundesministerium für Bildung und ForschungNational Institute on AgingNational Institute for Health and Care ResearchAgence Nationale de la RechercheUniversity College LondonHope Center for Neurological DisordersWellcome TrustNational Institutes of HealthRosetrees TrustEuropean CommissionGeorge Washington UniversityHunter Medical Research InstituteAflacNational Institute of Neurological Disorders and StrokeBritish Heart FoundationEmory UniversityRoyal Holloway, University of LondonBrigham and Women's HospitalYale UniversityUniversity of Texas Health Science Center at HoustonNational Heart, Lung, and Blood InstituteChildren’s Hospital of Wisconsin Research InstituteAmerican Heart Association
KeywordsGenome-wide association studyColocalizationIntima-media thicknessMedicineCardiologyInternal medicineCarotid arteriesBiologyGeneticsSingle-nucleotide polymorphismGenotypeNeuroscienceGene

Abstract

fetched live from OpenAlex

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.924
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

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.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.384
Teacher spread0.326 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it