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Record W2220222167

Common variants at 12q14 and 12q24 are associated with hippocampal volume

2012· article· en· W2220222167 on OpenAlexaff
Joshua C. Bis, Charles DeCarli, Albert V. Smith, Fedde van der Lijn, Fabrice Crivello, Myriam Fornage, Stéphanie Debette, Joshua M. Shulman, Helena Schmidt, Velandai Srikanth, Maaike Schuur, Lei Yu, Seung‐Hoan Choi, Sigurður Sigurðsson, Benjamin F.J. Verhaaren, Anita L. DeStefano, Jean‐Charles Lambert, Clifford R. Jack, Maksim Struchalin, Jim Stankovich, Carla A. Ibrahim‐Verbaas, Debra Fleischman, Alex Zijdenbos, Tom den Heijer, Bernard Mazoyer, Laura H. Coker, Christian Enzinger, Patrick Danoy, Najaf Amin, Konstantinos Arfanakis, Mark A. van Buchem, Renée F.A.G. de Bruijn, Alexa Beiser, Carole Dufouil, Juebin Huang, Margherita Cavalieri, Russell Thomson, Wiro J. Niessen, Lori B. Chibnik, Gauti Kjartan Gíslason, Albert Hofman, Aleksandra Pikula, Philippe Amouyel, Kevin B. Freeman, Thanh G. Phan, Ben A. Oostra, Jason L. Stein, Sarah E. Medland, Alejandro Arias Vásquez, Derrek P. Hibar, Margaret J. Wright, Barbara Franke, Nicholas G. Martin, Paul M. Thompson, Michael A. Nalls, André G. Uitterlinden, Rhoda Au, Alexis Elbaz, Richard Beare, John C. van Swieten, Oscar L. López, Tamara B. Harris, Vincent Chouraki, Monique M.B. Breteler, Philip L. De Jager, James T. Becker, Meike W. Vernooij, David S. Knopman, Franz Fazekas, Philip A. Wolf, Aad van der Lugt, Vilmundur Guðnason, W. T. Longstreth, Matthew A. Brown, David A. Bennett, Cornelia M. van Duijn, Thomas H. Mosley, Reinhold Schmidt, Christophe Tzourio, Lenore J. Launer, M. Arfan Ikram, Sudha Seshadri

Bibliographic record

VenueDigital Access to Scholarship at Harvard (DASH) (Harvard University) · 2012
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversité de Montréal
FundersNational Institute on Deafness and Other Communication DisordersNational Eye InstituteNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Institutes of HealthHjartavernd
KeywordsGenome-wide association studySNPSingle-nucleotide polymorphismHippocampal formationBiologyCognitive declineGeneticsDementiaGenetic associationHippocampusInternal medicineDiseaseEndocrinologyGeneMedicineGenotype
DOInot available

Abstract

fetched live from OpenAlex

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

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)0.002
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 score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.036
GPT teacher head0.272
Teacher spread0.236 · 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

Citations0
Published2012
Admission routes1
Has abstractyes

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