Record W2574432813 · doi:10.1038/ncomms13624

Novel genetic loci associated with hippocampal volume

2017· review· en· W2574432813 on OpenAlexaff

Derrek P. Hibar, Hieab H.H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Rentería, Joshua C. Bis, Alejandro Arias Vásquez, M. Kamran Ikram, Sylvane Desrivières, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Ashley Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuéllar-Partida, Fabrice Crivello, Anouk den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, O. Grimm, Michael Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Haß, Unn K. Haukvik, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Kjetil Nordbø Jørgensen, Nazanin Karbalai, Dalia Kasperavičiūtė, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, David C. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, André F. Marquand, Mar Matarín, Karen A. Mather, Manuel Mattheisen, David R. McKay, Yuri Milaneschi, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Paul Nyquist, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Lukas Pirpamer, Benno Pütz, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Stefan Ropele, Emma Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Arvin Saremi, Claudia L. Satizábal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Diana Tordesillas‐Gutiérrez, Roberto Toro, Daniah Trabzuni, Stella Trompet, Dhananjay Vaidya, Jeroen van der Grond, Sven J. van der Lee, Dennis van der Meer, Marjolein M. J. van Donkelaar, Kristel R. van Eijk, Theo G.M. van Erp, Daan van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, B. Gwen Windham, Anderson M. Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Ching‐Yu Cheng, Sven Cichon, Mark Cookson, Aiden Corvin, Benedicto Crespo‐Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Anton J. M. de Craen, Eco J. C. de Geus, Philip L. De Jager, Greig I. de Zubicaray, Ian J. Deary, Stéphanie Debette, Charles DeCarli, Norman Delanty, Chantal Depondt, Anita L. DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Christian Enzinger, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra Fleischman, Ian Ford, Myriam Fornage, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H.H. Göring, Robert C. Green, Oliver Gruber, Vilmundur Guðnason, Sebastian Guelfi, Asta K. Håberg, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stéphanie Le Hellard, Dena Hernández, Dirk J. Heslenfeld, Beng‐Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Georg Homuth, Norbert Hosten, Jouke‐Jan Hottenga, Matthew J. Huentelman, Hilleke E. Hulshoff Pol, Masashi Ikeda, Clifford R. Jack, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kłoszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean‐Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Francis J. McMahon, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer‐Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller‐Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomáš Paus, Zdenka Pausová, Brenda W.J.H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk‐Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Helena Schmidt, Peter R. Schofield, Sigurdur Sigursson, Andrew Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan C. Troncoso, Magda Tsolaki, Christophe Tzourio, André G. Uitterlinden, Maria C. Valdés Hernández, Marcel van der Brug, Aad van der Lugt, Nic J.A. van der Wee, Neeltje E. M. van Haren, Dennis van ‘t Ent, Marie‐José van Tol, Badri N. Vardarajan, Bruno Vellas, Dick J. Veltman, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, D.R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Yin Wong, Clinton B. Wright, Ronald H. Zielke, Alan B. Zonderman, Nicholas G. Martin, Cornelia M. van Duijn, Margaret J. Wright, W. T. Longstreth, Günter Schumann, Hans J. Grabe, Barbara Franke, Lenore J. Launer, Sarah E. Medland, Sudha Seshadri, Paul M. Thompson, M. Arfan Ikram

Bibliographic record

VenueNature Communications · 2017

Typereview

Languageen

FieldBiochemistry, Genetics and Molecular Biology

TopicEpigenetics and DNA Methylation

Canadian institutionsBaycrest HospitalBioPhage Pharma (Canada)SickKids FoundationMontreal Neurological Institute and HospitalUniversity of TorontoCanada Research ChairsUniversity of CalgaryDouglas Mental Health University InstituteMcGill UniversityHospital for Sick Children

FundersU.S. National Library of MedicineNational Institute of Biomedical Imaging and BioengineeringVifor PharmaNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Institute for Health and Care ResearchNational Institute of Neurological Disorders and StrokeMedical Research CouncilAlzheimer's Disease Neuroimaging InitiativeParkinson's UKLundbeckfondenNational Center for Advancing Translational SciencesWellcome Trust

KeywordsHippocampal formationVolume (thermodynamics)Computational biologyBiologyNeuroscienceComputer sciencePhysics

DOI10.1038/ncomms13624

Abstract

fetched live from OpenAlex

Abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes ( ASTN2 , DPP4 and MAST4 ) and one is found 200 kb upstream of SHH . A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease ( r g =−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

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)0.001

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 score0.996

Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

Category	Codex	Gemma
Metaresearch	0.000	0.001
Meta-epidemiology (narrow)	0.000	0.000
Meta-epidemiology (broad)	0.001	0.000
Bibliometrics	0.000	0.000
Science and technology studies	0.000	0.000
Scholarly communication	0.000	0.000
Open science	0.002	0.001
Research integrity	0.001	0.001
Insufficient payload (model declined to judge)	0.000	0.000

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 head0.071

GPT teacher head0.374

Teacher spread0.303 · 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.

Meta-epidemiology (narrow)Research integrity

Study designNot applicable

Domainnot available

GenreReview

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".

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Citations335

Published2017

Admission routes1

Has abstractyes

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