Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eatin...

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Autores: Mercader Bigas, Josep Maria, Saus Martínez, Ester, Agüera, Zaida, Bayés, Mònica, Boni, Claudette, Carreras, Anna, Cellini, Elena, Cid Ibeas, Rafael de, Dierssen, Mara, Escaramís, Geòrgia, Fernández Aranda, Fernando, Forcano, Laura, Gallego, Xavier, González Ruiz, Juan Ramón, Gorwood, Philip, Hebebrand, Johannes, Hinney, Anke, Nacmias, Benedetta, Puig, Anna, Ribasés, Marta, Ricca, Valdo, Romo, Lucía, Sorbi, Sandro, Versini, Audrey, Gratacós Mayora, Mònica, Estivill, Xavier, 1955-
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2008
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/16493
Acceso en línea:http://hdl.handle.net/10230/16493
http://dx.doi.org/10.1093/hmg/ddn013
Access Level:acceso abierto
Palabra clave:Trastorns de la conducta alimentària -- Aspectes genètics
Trastorns de la conducta alimentària -- Models animals
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spelling Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disordersMercader Bigas, Josep MariaSaus Martínez, EsterAgüera, ZaidaBayés, MònicaBoni, ClaudetteCarreras, AnnaCellini, ElenaCid Ibeas, Rafael deDierssen, MaraEscaramís, GeòrgiaFernández Aranda, FernandoForcano, LauraGallego, XavierGonzález Ruiz, Juan RamónGorwood, PhilipHebebrand, JohannesHinney, AnkeNacmias, BenedettaPuig, AnnaRibasés, MartaRicca, ValdoRomo, LucíaSorbi, SandroVersini, AudreyGratacós Mayora, MònicaEstivill, Xavier, 1955-Trastorns de la conducta alimentària -- Aspectes genèticsTrastorns de la conducta alimentària -- Models animalsEating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.Oxford University Press201220122008info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/16493http://dx.doi.org/10.1093/hmg/ddn013reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésHuman Molecular Genetics. 2008;17(9):1234-44© 2008 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version: Mercader JM, Saus E, Agüera Z, Bayés M, Boni C, Carreras A, Cellini E, de Cid R, Dierssen M, Escaramís G, Fernández-Aranda F, Forcano L, Gallego X, González JR, Gorwood P, Hebebrand J, Hinney A, Nacmias B, Puig A, Ribasés M, Ricca V, Romo L, Sorbi S, Versini A, Gratacòs M, Estivill X. Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders. Hum Mol Genet. 2008; 17(9): 1234-44. DOI: 10.1093/hmg/ddn013 is available online at http://hmg.oxfordjournals.org/content/17/9/1234info:eu-repo/semantics/openAccessoai:recercat.cat:10230/164932026-05-29T05:05:01Z
dc.title.none.fl_str_mv Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
title Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
spellingShingle Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
Mercader Bigas, Josep Maria
Trastorns de la conducta alimentària -- Aspectes genètics
Trastorns de la conducta alimentària -- Models animals
title_short Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
title_full Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
title_fullStr Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
title_full_unstemmed Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
title_sort Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders
dc.creator.none.fl_str_mv Mercader Bigas, Josep Maria
Saus Martínez, Ester
Agüera, Zaida
Bayés, Mònica
Boni, Claudette
Carreras, Anna
Cellini, Elena
Cid Ibeas, Rafael de
Dierssen, Mara
Escaramís, Geòrgia
Fernández Aranda, Fernando
Forcano, Laura
Gallego, Xavier
González Ruiz, Juan Ramón
Gorwood, Philip
Hebebrand, Johannes
Hinney, Anke
Nacmias, Benedetta
Puig, Anna
Ribasés, Marta
Ricca, Valdo
Romo, Lucía
Sorbi, Sandro
Versini, Audrey
Gratacós Mayora, Mònica
Estivill, Xavier, 1955-
author Mercader Bigas, Josep Maria
author_facet Mercader Bigas, Josep Maria
Saus Martínez, Ester
Agüera, Zaida
Bayés, Mònica
Boni, Claudette
Carreras, Anna
Cellini, Elena
Cid Ibeas, Rafael de
Dierssen, Mara
Escaramís, Geòrgia
Fernández Aranda, Fernando
Forcano, Laura
Gallego, Xavier
González Ruiz, Juan Ramón
Gorwood, Philip
Hebebrand, Johannes
Hinney, Anke
Nacmias, Benedetta
Puig, Anna
Ribasés, Marta
Ricca, Valdo
Romo, Lucía
Sorbi, Sandro
Versini, Audrey
Gratacós Mayora, Mònica
Estivill, Xavier, 1955-
author_role author
author2 Saus Martínez, Ester
Agüera, Zaida
Bayés, Mònica
Boni, Claudette
Carreras, Anna
Cellini, Elena
Cid Ibeas, Rafael de
Dierssen, Mara
Escaramís, Geòrgia
Fernández Aranda, Fernando
Forcano, Laura
Gallego, Xavier
González Ruiz, Juan Ramón
Gorwood, Philip
Hebebrand, Johannes
Hinney, Anke
Nacmias, Benedetta
Puig, Anna
Ribasés, Marta
Ricca, Valdo
Romo, Lucía
Sorbi, Sandro
Versini, Audrey
Gratacós Mayora, Mònica
Estivill, Xavier, 1955-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trastorns de la conducta alimentària -- Aspectes genètics
Trastorns de la conducta alimentària -- Models animals
topic Trastorns de la conducta alimentària -- Aspectes genètics
Trastorns de la conducta alimentària -- Models animals
description Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.
publishDate 2008
dc.date.none.fl_str_mv 2008
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/16493
http://dx.doi.org/10.1093/hmg/ddn013
url http://hdl.handle.net/10230/16493
http://dx.doi.org/10.1093/hmg/ddn013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Human Molecular Genetics. 2008;17(9):1234-44
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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