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Record W2626604457 · doi:10.1038/s41598-017-01674-8

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

2017· article· en· W2626604457 on OpenAlexaff
Dong Li, Xiao Chang, John J. Connolly, Lifeng Tian, Yichuan Liu, Elizabeth Bhoj, Nora Robinson, Debra Abrams, Leslie A. Lange, Jonathan P. Bradfield, Cecilia E. Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Yiran Guo, Haijun Qiu, Frank Mentch, Kelly Thomas, Rosetta Chiavacci, Roger D. Cone, Bingshan Li, Patrick Sleiman, Vesna Boraska Perica, Christopher S. Franklin, James Floyd, Laura M. Thornton, Laura M. Huckins, Lorraine Southam, N. William Rayner, Ioanna Tachmazidou, Kelly L. Klump, Janet Treasure, Ulrike Schmidt, Federica Tozzi, Kirsty Kiezebrink, Johannes Hebebrand, Philip Gorwood, Roger A.H. Adan, Martien J. Kas, Angela Favaro, Paolo Santonastaso, Fernando Fernández‐Aranda, Mónica Gratacòs, Filip Rybakowski, Monika Dmitrzak‐Węglarz, Jaakko Kaprio, Anna Keski‐Rahkonen, Anu Raevuori, Eric F. van Furth, M Landt, James I. Hudson, Ted Reichborn‐Kjennerud, Gun Peggy Knudsen, Palmiero Monteleone, Allan S. Kaplan, Andreas Karwautz, Wade H. Berrettini, Nicholas J. Schork, Tetsuya Ando, Hidetoshi Inoko, Tõnu Esko, Krista Fischer, Katrin Männik, Andres Metspalu, Jessica H. Baker, Janiece E. DeSocio, Christopher Hilliard, Julie K. O’Toole, Jacques Pantel, Jin P. Szatkiewicz, Stephanie Zerwas, Oliver S. P. Davis, Sietske G. Helder, Katharina Bühren, Roland Burghardt, Martina de Zwaan, Karin Egberts, Stefan Ehrlich, Beate Herpertz‐Dahlmann, Wolfgang Herzog, Hartmut Imgart, André Scherag, Stephan Zipfel, Claudette Boni, Nicolás Ramoz, Audrey Versini, Unna N. Danner, Judith Hendriks, Bobby P.C. Koeleman, Roel A. Ophoff, Eric Strengman, Annemarie Elburg, Alice Bruson, Maurizio Clementi, Daniela Degortes, Monica Forzan, Elena Tenconi, Elisa Docampo, Geòrgia Escaramís, Susana Jiménez‐Múrcia, Jolanta Lissowska, Andrzej Rajewski, Neonila Szeszenia‐Dąbrowska, Agnieszka Slopien, Joanna Hauser, Leila Karhunen, Ingrid Meulenbelt, P. Eline Slagboom, Alfonso Tortorella, Mario Maj, George Dedoussis, Dimitris Dikeos, Fragiskos Gonidakis, Konstantinos Tziouvas, Άρτεμις Τσίτσικα, Hana Papežová, Lenka Šlachtová, Debora Martaskova, James L. Kennedy, Robert D. Levitan, Zeynep Yılmaz, Julia Huemer, Doris Koubek, Elisabeth Merl, Gudrun Wagner, Paul Lichtenstein, Gerome Breen, Sarah Cohen‐Woods, Anne Farmer, Peter McGuffin, Sven Cichon, Ina Giegling, Stefan Herms, Dan Rujescu, Stefan Schreiber, H-Erich Wichmann, Christian Dina, Robert Sladek, Giovanni Gambaro, Nicole Soranzo, Antonio Julià, Sara Marsal, Raquel Rabionet, Valérie Gaborieau, Danielle M. Dick, Aarno Palotie, Samuli Ripatti, Elisabeth Widén, Ole A. Andreassen, Thomas Espeseth, Astri J. Lundervold, Ivar Reinvang, Vidar M. Steen, Stéphanie Le Hellard, Morten Mattingsdal, Ιωάννα Ντάλλα, Vladimír Bencko, Lenka Foretová, Vladimí­r Janout, Marie Navratilova, Steven Gallinger, Dalila Pinto, Stephen W. Scherer, H.N. Aschauer, Laura Carlberg, Alexandra Schosser, Lars Alfredsson, Bo Ding, Lars Klareskog, Leonid Padyukov, Chris Finan, Gursharan Kalsi, Marion Roberts, Jeff Barrett, Xavier Estivill, Anke Hinney, Patrick F. Sullivan, Eleftheria Zeggini, Cynthia M. Bulik, Harry Brandt, Steve Crawford, Scott J. Crow, Manfred M. Fichter, Katherine A. Halmi, Craig Johnson, Maria C. La Via, James E. Mitchell, Michael Strober, Alessandro Rotondo, D. Blake Woodside, Pamela K. Keel, Lisa Lilenfeld, Andrew W. Bergen, Wade Berrettini, Walter H. Kaye, Pierre J. Magistretti, Håkon Håkonarson

Bibliographic record

VenueScientific Reports · 2017
Typearticle
Languageen
FieldNeuroscience
TopicRegulation of Appetite and Obesity
Canadian institutionsToronto General HospitalUniversity of TorontoUniversity Health NetworkHospital for Sick ChildrenMcGill University and Génome Québec Innovation CentreLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalCentre for Addiction and Mental Health
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Mental HealthChildren's Hospital of Philadelphia
KeywordsGenome-wide association studySingle-nucleotide polymorphismLocus (genetics)Genetic associationPhenotypeGeneticsBiologyLeptinSNPBioinformaticsGeneEndocrinologyGenotypeObesity

Abstract

fetched live from OpenAlex

Abstract We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10−7; OR = 0.7; 95% confidence interval (CI) = 0.61–0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.022
GPT teacher head0.272
Teacher spread0.250 · 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

Citations36
Published2017
Admission routes1
Has abstractyes

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Same venueScientific ReportsSame topicRegulation of Appetite and ObesityFrench-language works237,207