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Record W3003733514 · doi:10.1038/s41598-020-58291-1

Genome-Wide Association Study of Brain Connectivity Changes for Alzheimer’s Disease

2020· article· en· W3003733514 on OpenAlexfundno aff
Samar S. M. Elsheikh, Emile R. Chimusa, Nicola Mulder, Alessandro Crimi

Bibliographic record

VenueScientific Reports · 2020
Typearticle
Languageen
FieldMedicine
TopicAdvanced Neuroimaging Techniques and Applications
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierAlzheimer's Disease Neuroimaging InitiativeOrganization for Women in Science for the Developing WorldEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaUniversity of Southern CaliforniaF. Hoffmann-La RocheStyrelsen för Internationellt UtvecklingssamarbeteNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbMeso Scale DiagnosticsUniversity of Cape TownAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsGenome-wide association studyNeuroimagingDiseaseAlzheimer's diseaseAlzheimer's Disease Neuroimaging InitiativeGenetic associationSingle-nucleotide polymorphismImaging geneticsNeuroscienceComputational biologyBiologyBioinformaticsMedicineGeneticsGeneGenotypePathology

Abstract

fetched live from OpenAlex

Variations in the human genome have been found to be an essential factor that affects susceptibility to Alzheimer's disease. Genome-wide association studies (GWAS) have identified genetic loci that significantly contribute to the risk of Alzheimers. The availability of genetic data, coupled with brain imaging technologies have opened the door for further discoveries, by using data integration methodologies and new study designs. Although methods have been proposed for integrating image characteristics and genetic information for studying Alzheimers, the measurement of disease is often taken at a single time point, therefore, not allowing the disease progression to be taken into consideration. In longitudinal settings, we analyzed neuroimaging and single nucleotide polymorphism datasets obtained from the Alzheimer's Disease Neuroimaging Initiative for three clinical stages of the disease, including healthy control, early mild cognitive impairment and Alzheimer's disease subjects. We conducted a GWAS regressing the absolute change of global connectivity metrics on the genetic variants, and used the GWAS summary statistics to compute the gene and pathway scores. We observed significant associations between the change in structural brain connectivity defined by tractography and genes, which have previously been reported to biologically manipulate the risk and progression of certain neurodegenerative disorders, including Alzheimer's disease.

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 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)0.000
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation 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 score0.273
Threshold uncertainty score0.274

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.115
GPT teacher head0.367
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 teacher head, 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

Citations45
Published2020
Admission routes1
Has abstractyes

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