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Record W3193978193 · doi:10.1101/2021.08.20.21261814

Comprehensive genetic analysis of the human lipidome identifies novel loci controlling lipid homeostasis with links to coronary artery disease

2021· preprint· en· W3193978193 on OpenAlexaff
Gemma Cadby, Corey Giles, Phillip E. Melton, Kevin Huynh, Natalie A. Mellett, Thy Duong, Thu Anh Nguyen, Michelle Cinel, Alexander Smith, Gavriel Olshansky, Tingting Wang, Marta Brożyńska, Nina S. McCarthy, Amir Ariff, Joseph Hung, Jennie Hui, John Beilby, Marie‐Pierre Dubé, Gerald F. Watts, Sonia Shah, Naomi R. Wray, Wei Ling Florence Lim, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Tenielle Porter, Michaël Vacher, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Xianlin Han, Rima Kaddurah‐Daouk, Ralph N. Martins, John Blangero, Peter J. Meikle, Eric K. Moses

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldMedicine
TopicLipid metabolism and disorders
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersAustralian GovernmentState Government of VictoriaDementia AustraliaEdith Cowan UniversityGovernment of Western AustraliaDementia Collaborative Research Centres, AustraliaNational Institutes of HealthNational Cancer InstituteHealthwayNational Health and Medical Research CouncilCommonwealth Scientific and Industrial Research OrganisationMedical Research CouncilNational Institute on AgingScience and Industry Endowment Fund
KeywordsLipidomeBiologyLipidomicsLipid metabolismGenome-wide association studyEndophenotypeCoronary artery diseaseGeneticsGenetic architectureLocus (genetics)DiseaseComputational biologyBioinformaticsSingle-nucleotide polymorphismMedicineInternal medicineGeneQuantitative trait locusEndocrinologyGenotypeNeuroscience

Abstract

fetched live from OpenAlex

Abstract We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 phenotyped individuals from the Busselton Health Study. In our discovery GWAS we identified 667 independent loci associations with these lipid species (479 novel), followed by meta-analysis and validation in two independent cohorts. Lipid endophenotypes (134) identified for CAD were associated with variation at 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P<1×10 −3 ), 43 loci were associated with at least one of the 134 lipid endophenotypes. The findings of this study illustrate the value of integrative biology to investigate the genetics and lipid metabolism in the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.024
GPT teacher head0.271
Teacher spread0.246 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2021
Admission routes1
Has abstractyes

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