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; 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-

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

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dc.contributor.author Mercader Bigas, Josep Mariaca
dc.contributor.author Saus Martínez, Esterca
dc.contributor.author Agüera, Zaidaca
dc.contributor.author Bayés, Mònicaca
dc.contributor.author Boni, Claudetteca
dc.contributor.author Carreras, Annaca
dc.contributor.author Cellini, Elenaca
dc.contributor.author Cid Ibeas, Rafael deca
dc.contributor.author Dierssen, Maraca
dc.contributor.author Escaramís, Geòrgiaca
dc.contributor.author Fernández Aranda, Fernandoca
dc.contributor.author Forcano, Lauraca
dc.contributor.author Gallego, Xavierca
dc.contributor.author González Ruiz, Juan Ramónca
dc.contributor.author Gorwood, Philipca
dc.contributor.author Hebebrand, Johannesca
dc.contributor.author Hinney, Ankeca
dc.contributor.author Nacmias, Benedettaca
dc.contributor.author Puig, Annaca
dc.contributor.author Ribasés, Martaca
dc.contributor.author Ricca, Valdoca
dc.contributor.author Romo, Lucíaca
dc.contributor.author Sorbi, Sandroca
dc.contributor.author Versini, Audreyca
dc.contributor.author Gratacós Mayora, Mònicaca
dc.contributor.author Estivill, Xavier, 1955-ca
dc.date.accessioned 2012-05-31T10:32:53Z
dc.date.available 2012-05-31T10:32:53Z
dc.date.issued 2008ca
dc.description.abstract 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.
dc.format.mimetype application/pdfca
dc.identifier.citation Mercader JM, Saus E, Agüera Z, Bayés M, Boni C, Carreras A et al. 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/ddn013ca
dc.identifier.doi http://dx.doi.org/10.1093/hmg/ddn013
dc.identifier.issn 0964-6906ca
dc.identifier.uri http://hdl.handle.net/10230/16493
dc.language.iso engca
dc.publisher Oxford University Pressca
dc.relation.ispartof Human Molecular Genetics. 2008;17(9):1234-44
dc.rights © 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/17/9/1234ca
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Trastorns de la conducta alimentària -- Aspectes genètics
dc.subject.other Trastorns de la conducta alimentària -- Models animals
dc.title Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disordersca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/submittedVersion

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