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Record W4388283999 · doi:10.1038/s42003-023-05454-1

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults

2023· article· en· W4388283999 on OpenAlexaff
Adrienne Tin, Alison E. Fohner, Qiong Yang, Jennifer A. Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V. Lindbohm, Michael R. Duggan, Osorio Meirelles, Sarah E. Harris, Valborg Guðmundsdóttir, Adele M. Taylor, Albert Henry, Alexa Beiser, Ali Shojaie, Annabell Coors, Annette L. Fitzpatrick, Claudia Langenberg, Claudia L. Satizábal, Colleen M. Sitlani, Eleanor Wheeler, Elliot M. Tucker–Drob, Jan Bressler, Josef Coresh, Joshua C. Bis, Julián Candia, Lori L. Jennings, Maik Pietzner, Mark Lathrop, Oscar L. López, Paul Redmond, Robert E. Gerszten, Stephen S. Rich, Susan R. Heckbert, Thomas R. Austin, Timothy M. Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S. Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I. Rotter, Keenan A. Walker, Luigi Ferrucci, Mika Kivimäki, Monique M.B. Breteler, Simon R. Cox, Stéphanie Debette, Thomas H. Mosley, Vilmundur Guðnason, Lenore J. Launer, Bruce M. Psaty, Sudha Seshadri, Myriam Fornage

Bibliographic record

VenueCommunications Biology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMachine Learning in Bioinformatics
Canadian institutionsMcGill Genome Centre
FundersNational Institute of Neurological Disorders and StrokeNational Institute on Deafness and Other Communication DisordersNational Human Genome Research InstituteNational Institute on Drug AbuseNational Heart, Lung, and Blood InstituteNational Institute on AgingBiotechnology and Biological Sciences Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilHjartaverndAge UKUniversité de BordeauxFondation de FranceBundesministerium für Bildung und ForschungFondation pour la Recherche MédicaleInstitut National de la Santé et de la Recherche MédicaleDeutsches Zentrum für Neurodegenerative ErkrankungenDeutsche ForschungsgemeinschaftU.S. Department of Health and Human ServicesEconomic and Social Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesSanofiEuropean CommissionNational Center for Research ResourcesAgence Nationale de la RechercheScottish GovernmentMutuelle Générale de l'Education NationaleRoyal SocietyDirectorate for Biological SciencesNational Institutes of Health
KeywordsMendelian randomizationCognitionBiologyDiseaseDementiaAlzheimer's diseaseFunction (biology)NeuroscienceGeneticsBioinformaticsMedicineInternal medicineGeneGenotype

Abstract

fetched live from OpenAlex

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

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)0.000
metaresearch head score (Gemma)0.002
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 score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.017
GPT teacher head0.269
Teacher spread0.252 · 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

Citations22
Published2023
Admission routes1
Has abstractyes

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