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

Dong Li; Xiao Chang; John J. Connolly; Lifeng Tian; Yichuan Liu; Elizabeth J. Bhoj; Nora Robinson; Debra Abrams; Yun R. Li; Jonathan P. Bradfield; Cecilia E. Kim; Jin Li; Fengxiang Wang; James Snyder; Maria Lemma; Cuiping Hou; Zhi Wei; Yiran Guo; Haijun Qiu; Frank D. Mentch; Kelly A. Thomas; Rosetta M. Chiavacci; Roger Cone; Bingshan Li; Patrick A. Sleiman; Hakon Hakonarson; Vesna Boraska Perica; Christopher S. Franklin; James A. B. Floyd; Laura M. Thornton; Laura M. Huckins; Lorraine Southam; N. William Rayner; Ioanna Tachmazidou; Ulrike Schmidt; Federica Tozzi; Kirsty Kiezebrink; Johannes Hebebrand; Philip Gorwood; Roger A. H. Adan; Martien J. H. Kas; Angela Favaro; Paolo Santonastaso; Fernando Fernánde-Aranda; Monica Gratacos; Filip Rybakowski; Monika Dmitrzak-Weglarz; Jaakko Kaprio; Anna Keski-Rahkonen; Anu Raevuori-Helkamaa; Eric F. Van Furth; Margarita C. T. Slof-Opt Landt; James I. Hudson; Ted Reichborn-Kjennerud; Gun Peggy S. Knudsen; Palmiero Monteleone; Andreas Karwautz; Wade H. Berrettini; Nicholas J. Schork; Tetsuya Ando; Hidetoshi Inoko; Toñu Esko; Krista Fischer; Katrin Männik; Andres Metspalu; Jessica H. Baker; Janiece E. Desocio; Christopher E. Hilliard; Julie K. O'Toole; Jacques Pantel; Jin P. Szatkiewicz; Stephanie Zerwas; Oliver S. P. Davis; Sietske 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; Nicolas Ramoz; Audrey Versini; Unna N. Danner; Judith Hendriks; Bobby P. C. Koeleman; Roel A. Ophoff; Eric Strengman; Annemarie A. Van Elburg; Alice Bruson; Maurizio Clementi; Daniela Degortes; Monica Forzan; Elena Tenconi; Elisa Docampo; Geòrgia Escaramís; Susana Jiménez-Murcia; Jolanta Lissowska; Andrzej Rajewski; Neonila Szeszenia-Dabrowska; Agnieszka Slopien; Joanna Hauser; Leila Karhunen; Ingrid Meulenbelt; P. Eline Slagboom; Alfonso Tortorella; Mario Maj; George Dedoussis; Dimitris Dikeos; Fragiskos Gonidakis; Konstantinos Tziouvas; Artemis Tsitsika; Hana Papezova; Lenka Slachtova; Debora Martaskova; James L. Kennedy; Robert D. Levitan; Zeynep Yilmaz; 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; Rob Sladek; Giovanni Gambaro; Nicole Soranzo; Antonio Julia; Sara Marsal; Raquel Rabionet; Valerie Gaborieau; Danielle M. Dick; Aarno Palotie; Samuli Ripatti; Elisabeth Widén; Ole A. Andreassen; Thomas Espeseth; Astri Lundervold; Ivar Reinvang; Vidar M. Steen; Stephanie Le Hellard; Morten Mattingsdal; Ioanna Ntalla; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Marie Navratilova; Steven Gallinger; Dalila Pinto; Stephen W. Scherer; Harald Aschauer; Laura Carlberg; Alexandra Schosser; Lars Alfredsson; Bo Ding; Lars Klareskog; Leonid Padyukov; Chris Finan; Gursharan Kalsi; Marion Roberts; Jeff C. Barrett; Xavier Estivill; Anke Hinney; Patrick F. Sullivan; Eleftheria Zeggini; Cynthia M. Bulik; Harry Brandt; Steve Crawford; Scott Crow; Manfred M. Fichter; Katherine A. Halmi; Craig Johnson; Allan S. Kaplan; Maria C. La Via; James Mitchell; Michael Strober; Alessandro Rotondo; Janet Treasure; D. Blake Woodside; Pamela K. Keel; Kelly L. Klump; Lisa Lilenfeld; Andrew W. Bergen; Walter Kaye; Pierre Magistretti

doi:10.1038/s41598-017-01674-8

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

Dong Li, Xiao Chang, John J. Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J. Bhoj, Nora Robinson, Debra Abrams, Yun R. Li, Jonathan P. Bradfield, Cecilia E. Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Yiran Guo, Haijun Qiu, Frank D. MentchKelly A. Thomas, Rosetta M. Chiavacci, Roger Cone, Bingshan Li, Patrick A. Sleiman, Hakon Hakonarson, Vesna Boraska Perica, Christopher S. Franklin, James A. B. Floyd, Laura M. Thornton, Laura M. Huckins, Lorraine Southam, N. William Rayner, Ioanna Tachmazidou, Ulrike Schmidt, Federica Tozzi, Kirsty Kiezebrink, Johannes Hebebrand, Philip Gorwood, Roger A. H. Adan, Martien J. H. Kas, Angela Favaro, Paolo Santonastaso, Fernando Fernánde-Aranda, Monica Gratacos, Filip Rybakowski, Monika Dmitrzak-Weglarz, Jaakko Kaprio, Anna Keski-Rahkonen, Anu Raevuori-Helkamaa, Eric F. Van Furth, Margarita C. T. Slof-Opt Landt, James I. Hudson, Ted Reichborn-Kjennerud, Gun Peggy S. Knudsen, Palmiero Monteleone, Andreas Karwautz, Wade H. Berrettini, Nicholas J. Schork, Tetsuya Ando, Hidetoshi Inoko, Toñu Esko, Krista Fischer, Katrin Männik, Andres Metspalu, Jessica H. Baker, Janiece E. Desocio, Christopher E. Hilliard, Julie K. O'Toole, Jacques Pantel, Jin P. Szatkiewicz, Stephanie Zerwas, Oliver S. P. Davis, Sietske 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, Nicolas Ramoz, Audrey Versini, Unna N. Danner, Judith Hendriks, Bobby P. C. Koeleman, Roel A. Ophoff, Eric Strengman, Annemarie A. Van Elburg, Alice Bruson, Maurizio Clementi, Daniela Degortes, Monica Forzan, Elena Tenconi, Elisa Docampo, Geòrgia Escaramís, Susana Jiménez-Murcia, Jolanta Lissowska, Andrzej Rajewski, Neonila Szeszenia-Dabrowska, Agnieszka Slopien, Joanna Hauser, Leila Karhunen, Ingrid Meulenbelt, P. Eline Slagboom, Alfonso Tortorella, Mario Maj, George Dedoussis, Dimitris Dikeos, Fragiskos Gonidakis, Konstantinos Tziouvas, Artemis Tsitsika, Hana Papezova, Lenka Slachtova, Debora Martaskova, James L. Kennedy, Robert D. Levitan, Zeynep Yilmaz, 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, Rob Sladek, Giovanni Gambaro, Nicole Soranzo, Antonio Julia, Sara Marsal, Raquel Rabionet, Valerie Gaborieau, Danielle M. Dick, Aarno Palotie, Samuli Ripatti, Elisabeth Widén, Ole A. Andreassen, Thomas Espeseth, Astri Lundervold, Ivar Reinvang, Vidar M. Steen, Stephanie Le Hellard, Morten Mattingsdal, Ioanna Ntalla, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Marie Navratilova, Steven Gallinger, Dalila Pinto, Stephen W. Scherer, Harald Aschauer, Laura Carlberg, Alexandra Schosser, Lars Alfredsson, Bo Ding, Lars Klareskog, Leonid Padyukov, Chris Finan, Gursharan Kalsi, Marion Roberts, Jeff C. Barrett, Xavier Estivill, Anke Hinney, Patrick F. Sullivan, Eleftheria Zeggini, Cynthia M. Bulik, Harry Brandt, Steve Crawford, Scott Crow, Manfred M. Fichter, Katherine A. Halmi, Craig Johnson, Allan S. Kaplan, Maria C. La Via, James Mitchell, Michael Strober, Alessandro Rotondo, Janet Treasure, D. Blake Woodside, Pamela K. Keel, Kelly L. Klump, Lisa Lilenfeld, Andrew W. Bergen, Walter Kaye, Pierre Magistretti

Università Cattolica del Sacro Cuore

Risultato della ricerca: Contributo in rivista › Articolo in rivista

10 Citazioni (Scopus)

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 Ã 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.

Lingua originale	English
pagine (da-a)	3847-3855
Numero di pagine	9
Rivista	Scientific Reports
Volume	7
DOI	https://doi.org/10.1038/s41598-017-01674-8
Stato di pubblicazione	Pubblicato - 2017

Keywords

Multidisciplinary

Accesso al documento

10.1038/s41598-017-01674-8

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Cita questo

Li, D., Chang, X., Connolly, J. J., Tian, L., Liu, Y., Bhoj, E. J., Robinson, N., Abrams, D., Li, Y. R., Bradfield, J. P., Kim, C. E., Li, J., Wang, F., Snyder, J., Lemma, M., Hou, C., Wei, Z., Guo, Y., Qiu, H., ... Magistretti, P. (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7, 3847-3855. https://doi.org/10.1038/s41598-017-01674-8

@article{7dfff3a649a54d48a4f9c5cbb8016e5c,

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

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 {\~A} 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.",

keywords = "Multidisciplinary, Multidisciplinary",

author = "Dong Li and Xiao Chang and Connolly, {John J.} and Lifeng Tian and Yichuan Liu and Bhoj, {Elizabeth J.} and Nora Robinson and Debra Abrams and Li, {Yun R.} and Bradfield, {Jonathan P.} and Kim, {Cecilia E.} and Jin Li and Fengxiang Wang and James Snyder and Maria Lemma and Cuiping Hou and Zhi Wei and Yiran Guo and Haijun Qiu and Mentch, {Frank D.} and Thomas, {Kelly A.} and Chiavacci, {Rosetta M.} and Roger Cone and Bingshan Li and Sleiman, {Patrick A.} and Hakon Hakonarson and Perica, {Vesna Boraska} and Franklin, {Christopher S.} and Floyd, {James A. B.} and Thornton, {Laura M.} and Huckins, {Laura M.} and Lorraine Southam and Rayner, {N. William} and Ioanna Tachmazidou and Ulrike Schmidt and Federica Tozzi and Kirsty Kiezebrink and Johannes Hebebrand and Philip Gorwood and Adan, {Roger A. H.} and Kas, {Martien J. H.} and Angela Favaro and Paolo Santonastaso and Fernando Fern{\'a}nde-Aranda and Monica Gratacos and Filip Rybakowski and Monika Dmitrzak-Weglarz and Jaakko Kaprio and Anna Keski-Rahkonen and Anu Raevuori-Helkamaa and Furth, {Eric F. Van} and {Slof-Opt Landt}, {Margarita C. T.} and Hudson, {James I.} and Ted Reichborn-Kjennerud and Knudsen, {Gun Peggy S.} and Palmiero Monteleone and Andreas Karwautz and Berrettini, {Wade H.} and Schork, {Nicholas J.} and Tetsuya Ando and Hidetoshi Inoko and To{\~n}u Esko and Krista Fischer and Katrin M{\"a}nnik and Andres Metspalu and Baker, {Jessica H.} and Desocio, {Janiece E.} and Hilliard, {Christopher E.} and O'Toole, {Julie K.} and Jacques Pantel and Szatkiewicz, {Jin P.} and Stephanie Zerwas and Davis, {Oliver S. P.} and Sietske Helder and Katharina B{\"u}hren and Roland Burghardt and {De Zwaan}, Martina and Karin Egberts and Stefan Ehrlich and Beate Herpertz-Dahlmann and Wolfgang Herzog and Hartmut Imgart and Andr{\'e} Scherag and Stephan Zipfel and Claudette Boni and Nicolas Ramoz and Audrey Versini and Danner, {Unna N.} and Judith Hendriks and Koeleman, {Bobby P. C.} and Ophoff, {Roel A.} and Eric Strengman and {Van Elburg}, {Annemarie A.} and Alice Bruson and Maurizio Clementi and Daniela Degortes and Monica Forzan and Elena Tenconi and Elisa Docampo and Ge{\`o}rgia Escaram{\'i}s and Susana Jim{\'e}nez-Murcia and Jolanta Lissowska and Andrzej Rajewski and Neonila Szeszenia-Dabrowska and Agnieszka Slopien and Joanna Hauser and Leila Karhunen and Ingrid Meulenbelt and Slagboom, {P. Eline} and Alfonso Tortorella and Mario Maj and George Dedoussis and Dimitris Dikeos and Fragiskos Gonidakis and Konstantinos Tziouvas and Artemis Tsitsika and Hana Papezova and Lenka Slachtova and Debora Martaskova and Kennedy, {James L.} and Levitan, {Robert D.} and Zeynep Yilmaz and Julia Huemer and Doris Koubek and Elisabeth Merl and Gudrun Wagner and Paul Lichtenstein and Gerome Breen and Sarah Cohen-Woods and Anne Farmer and Peter Mcguffin and Sven Cichon and Ina Giegling and Stefan Herms and Dan Rujescu and Stefan Schreiber and H-Erich Wichmann and Christian Dina and Rob Sladek and Giovanni Gambaro and Nicole Soranzo and Antonio Julia and Sara Marsal and Raquel Rabionet and Valerie Gaborieau and Dick, {Danielle M.} and Aarno Palotie and Samuli Ripatti and Elisabeth Wid{\'e}n and Andreassen, {Ole A.} and Thomas Espeseth and Astri Lundervold and Ivar Reinvang and Steen, {Vidar M.} and {Le Hellard}, Stephanie and Morten Mattingsdal and Ioanna Ntalla and Vladimir Bencko and Lenka Foretova and Vladimir Janout and Marie Navratilova and Steven Gallinger and Dalila Pinto and Scherer, {Stephen W.} and Harald Aschauer and Laura Carlberg and Alexandra Schosser and Lars Alfredsson and Bo Ding and Lars Klareskog and Leonid Padyukov and Chris Finan and Gursharan Kalsi and Marion Roberts and Barrett, {Jeff C.} and Xavier Estivill and Anke Hinney and Sullivan, {Patrick F.} and Eleftheria Zeggini and Bulik, {Cynthia M.} and Harry Brandt and Steve Crawford and Scott Crow and Fichter, {Manfred M.} and Halmi, {Katherine A.} and Craig Johnson and Kaplan, {Allan S.} and {La Via}, {Maria C.} and James Mitchell and Michael Strober and Alessandro Rotondo and Janet Treasure and Woodside, {D. Blake} and Keel, {Pamela K.} and Klump, {Kelly L.} and Lisa Lilenfeld and Bergen, {Andrew W.} and Walter Kaye and Pierre Magistretti",

year = "2017",

doi = "10.1038/s41598-017-01674-8",

language = "English",

volume = "7",

pages = "3847--3855",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

Li, D, Chang, X, Connolly, JJ, Tian, L, Liu, Y, Bhoj, EJ, Robinson, N, Abrams, D, Li, YR, Bradfield, JP, Kim, CE, Li, J, Wang, F, Snyder, J, Lemma, M, Hou, C, Wei, Z, Guo, Y, Qiu, H, Mentch, FD, Thomas, KA, Chiavacci, RM, Cone, R, Li, B, Sleiman, PA, Hakonarson, H, Perica, VB, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernánde-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori-Helkamaa, A, Furth, EFV, Slof-Opt Landt, MCT, Hudson, JI, Reichborn-Kjennerud, T, Knudsen, GPS, Monteleone, P, Karwautz, A, Berrettini, WH, Schork, NJ, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, JH, Desocio, JE, Hilliard, CE, O'Toole, JK, Pantel, J, Szatkiewicz, JP, Zerwas, S, Davis, OSP, Helder, S, Bühren, K, Burghardt, R, De Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Danner, UN, Hendriks, J, Koeleman, BPC, Ophoff, RA, Strengman, E, Van Elburg, AA, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, PE, Tortorella, A, Maj, M, Dedoussis, G, Dikeos, D, Gonidakis, F, Tziouvas, K, Tsitsika, A, Papezova, H, Slachtova, L, Martaskova, D, Kennedy, JL, Levitan, RD, Yilmaz, Z, Huemer, J, Koubek, D, Merl, E, Wagner, G, Lichtenstein, P, Breen, G, Cohen-Woods, S, Farmer, A, Mcguffin, P, Cichon, S, Giegling, I, Herms, S, Rujescu, D, Schreiber, S, Wichmann, H-E, Dina, C, Sladek, R, Gambaro, G, Soranzo, N, Julia, A, Marsal, S, Rabionet, R, Gaborieau, V, Dick, DM, Palotie, A, Ripatti, S, Widén, E, Andreassen, OA, Espeseth, T, Lundervold, A, Reinvang, I, Steen, VM, Le Hellard, S, Mattingsdal, M, Ntalla, I, Bencko, V, Foretova, L, Janout, V, Navratilova, M, Gallinger, S, Pinto, D, Scherer, SW, Aschauer, H, Carlberg, L, Schosser, A, Alfredsson, L, Ding, B, Klareskog, L, Padyukov, L, Finan, C, Kalsi, G, Roberts, M, Barrett, JC, Estivill, X, Hinney, A, Sullivan, PF, Zeggini, E, Bulik, CM, Brandt, H, Crawford, S, Crow, S, Fichter, MM, Halmi, KA, Johnson, C, Kaplan, AS, La Via, MC, Mitchell, J, Strober, M, Rotondo, A, Treasure, J, Woodside, DB, Keel, PK, Klump, KL, Lilenfeld, L, Bergen, AW, Kaye, W & Magistretti, P 2017, 'A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling', Scientific Reports, vol. 7, pagg. 3847-3855. https://doi.org/10.1038/s41598-017-01674-8

TY - JOUR

T1 - A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

AU - Li, Dong

AU - Chang, Xiao

AU - Connolly, John J.

AU - Tian, Lifeng

AU - Liu, Yichuan

AU - Bhoj, Elizabeth J.

AU - Robinson, Nora

AU - Abrams, Debra

AU - Li, Yun R.

AU - Bradfield, Jonathan P.

AU - Kim, Cecilia E.

AU - Li, Jin

AU - Wang, Fengxiang

AU - Snyder, James

AU - Lemma, Maria

AU - Hou, Cuiping

AU - Wei, Zhi

AU - Guo, Yiran

AU - Qiu, Haijun

AU - Mentch, Frank D.

AU - Thomas, Kelly A.

AU - Chiavacci, Rosetta M.

AU - Cone, Roger

AU - Li, Bingshan

AU - Sleiman, Patrick A.

AU - Hakonarson, Hakon

AU - Perica, Vesna Boraska

AU - Franklin, Christopher S.

AU - Floyd, James A. B.

AU - Thornton, Laura M.

AU - Huckins, Laura M.

AU - Southam, Lorraine

AU - Rayner, N. William

AU - Tachmazidou, Ioanna

AU - Schmidt, Ulrike

AU - Tozzi, Federica

AU - Kiezebrink, Kirsty

AU - Hebebrand, Johannes

AU - Gorwood, Philip

AU - Adan, Roger A. H.

AU - Kas, Martien J. H.

AU - Favaro, Angela

AU - Santonastaso, Paolo

AU - Fernánde-Aranda, Fernando

AU - Gratacos, Monica

AU - Rybakowski, Filip

AU - Dmitrzak-Weglarz, Monika

AU - Kaprio, Jaakko

AU - Keski-Rahkonen, Anna

AU - Raevuori-Helkamaa, Anu

AU - Furth, Eric F. Van

AU - Slof-Opt Landt, Margarita C. T.

AU - Hudson, James I.

AU - Reichborn-Kjennerud, Ted

AU - Knudsen, Gun Peggy S.

AU - Monteleone, Palmiero

AU - Karwautz, Andreas

AU - Berrettini, Wade H.

AU - Schork, Nicholas J.

AU - Ando, Tetsuya

AU - Inoko, Hidetoshi

AU - Esko, Toñu

AU - Fischer, Krista

AU - Männik, Katrin

AU - Metspalu, Andres

AU - Baker, Jessica H.

AU - Desocio, Janiece E.

AU - Hilliard, Christopher E.

AU - O'Toole, Julie K.

AU - Pantel, Jacques

AU - Szatkiewicz, Jin P.

AU - Zerwas, Stephanie

AU - Davis, Oliver S. P.

AU - Helder, Sietske

AU - Bühren, Katharina

AU - Burghardt, Roland

AU - De Zwaan, Martina

AU - Egberts, Karin

AU - Ehrlich, Stefan

AU - Herpertz-Dahlmann, Beate

AU - Herzog, Wolfgang

AU - Imgart, Hartmut

AU - Scherag, André

AU - Zipfel, Stephan

AU - Boni, Claudette

AU - Ramoz, Nicolas

AU - Versini, Audrey

AU - Danner, Unna N.

AU - Hendriks, Judith

AU - Koeleman, Bobby P. C.

AU - Ophoff, Roel A.

AU - Strengman, Eric

AU - Van Elburg, Annemarie A.

AU - Bruson, Alice

AU - Clementi, Maurizio

AU - Degortes, Daniela

AU - Forzan, Monica

AU - Tenconi, Elena

AU - Docampo, Elisa

AU - Escaramís, Geòrgia

AU - Jiménez-Murcia, Susana

AU - Lissowska, Jolanta

AU - Rajewski, Andrzej

AU - Szeszenia-Dabrowska, Neonila

AU - Slopien, Agnieszka

AU - Hauser, Joanna

AU - Karhunen, Leila

AU - Meulenbelt, Ingrid

AU - Slagboom, P. Eline

AU - Tortorella, Alfonso

AU - Maj, Mario

AU - Dedoussis, George

AU - Dikeos, Dimitris

AU - Gonidakis, Fragiskos

AU - Tziouvas, Konstantinos

AU - Tsitsika, Artemis

AU - Papezova, Hana

AU - Slachtova, Lenka

AU - Martaskova, Debora

AU - Kennedy, James L.

AU - Levitan, Robert D.

AU - Yilmaz, Zeynep

AU - Huemer, Julia

AU - Koubek, Doris

AU - Merl, Elisabeth

AU - Wagner, Gudrun

AU - Lichtenstein, Paul

AU - Breen, Gerome

AU - Cohen-Woods, Sarah

AU - Farmer, Anne

AU - Mcguffin, Peter

AU - Cichon, Sven

AU - Giegling, Ina

AU - Herms, Stefan

AU - Rujescu, Dan

AU - Schreiber, Stefan

AU - Wichmann, H-Erich

AU - Dina, Christian

AU - Sladek, Rob

AU - Gambaro, Giovanni

AU - Soranzo, Nicole

AU - Julia, Antonio

AU - Marsal, Sara

AU - Rabionet, Raquel

AU - Gaborieau, Valerie

AU - Dick, Danielle M.

AU - Palotie, Aarno

AU - Ripatti, Samuli

AU - Widén, Elisabeth

AU - Andreassen, Ole A.

AU - Espeseth, Thomas

AU - Lundervold, Astri

AU - Reinvang, Ivar

AU - Steen, Vidar M.

AU - Le Hellard, Stephanie

AU - Mattingsdal, Morten

AU - Ntalla, Ioanna

AU - Bencko, Vladimir

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Navratilova, Marie

AU - Gallinger, Steven

AU - Pinto, Dalila

AU - Scherer, Stephen W.

AU - Aschauer, Harald

AU - Carlberg, Laura

AU - Schosser, Alexandra

AU - Alfredsson, Lars

AU - Ding, Bo

AU - Klareskog, Lars

AU - Padyukov, Leonid

AU - Finan, Chris

AU - Kalsi, Gursharan

AU - Roberts, Marion

AU - Barrett, Jeff C.

AU - Estivill, Xavier

AU - Hinney, Anke

AU - Sullivan, Patrick F.

AU - Zeggini, Eleftheria

AU - Bulik, Cynthia M.

AU - Brandt, Harry

AU - Crawford, Steve

AU - Crow, Scott

AU - Fichter, Manfred M.

AU - Halmi, Katherine A.

AU - Johnson, Craig

AU - Kaplan, Allan S.

AU - La Via, Maria C.

AU - Mitchell, James

AU - Strober, Michael

AU - Rotondo, Alessandro

AU - Treasure, Janet

AU - Woodside, D. Blake

AU - Keel, Pamela K.

AU - Klump, Kelly L.

AU - Lilenfeld, Lisa

AU - Bergen, Andrew W.

AU - Kaye, Walter

AU - Magistretti, Pierre

PY - 2017

Y1 - 2017

N2 - 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 Ã 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.

AB - 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 Ã 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.

KW - Multidisciplinary

UR - http://hdl.handle.net/10807/116495

UR - http://www.nature.com/srep/index.html

U2 - 10.1038/s41598-017-01674-8

DO - 10.1038/s41598-017-01674-8

M3 - Article

SN - 2045-2322

VL - 7

SP - 3847

EP - 3855

JO - Scientific Reports

JF - Scientific Reports

ER -

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

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