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

Dong Li; Xiao Chang; John J.M. Connolly; Lifeng Tian; Yichuan Liu; Elizabeth J. Bhoj; Nora Robinson; Debra J. Abrams; Yun R. Li; Jonathan P. Bradfield; Cecilia E. Kim; Jin Li; Fengxiang Wang; James Snyder; Maria Lemma; Cuiping Hou; Zhi Wei; Y. Guo; Haijun Qiu; Frank D. Mentch; Kelly A. Thomas; Rosetta M. Chiavacci; Roger D. Cone; Bingshan Li; Patrick M.A. Sleiman; Håkon H. Håkonarson; Vesna Boraska Perica; Christopher S. Franklin; James A.B. Floyd; Laura Marie Thornton; Laura M. Huckins; Lorraine Southam; Nigel William Rayner; Ioanna Tachmazidou; Ulrike H. Schmidt; Federica Tozzi; Kirsty Kiezebrink; Johannes Hebebrand; Philip A.P.M. Gorwood; Roger A.H. Adan; Martien J.H. Kas; Angela Favaro; Paolo Santonastaso; Fernando Fernánde-Aranda; Mònica Gratacòs; Filip Rybakowski; Monika Paulina 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 Knudsen; Palmiero Monteleone; Andreas F.K. 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 E. Hilliard; Julie K. O'Toole; Jacques Pantel; Jin Peng Szatkiewicz; Stephanie C. Zerwas; Oliver S.P. Davis; Sietske G. Helder; Katharina Bühren; Roland Burghardt; Martina De Zwaan; Karin Maria Egberts; Stefan Ehrlich; Beate M. 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; R. A. Ophoff; Eric Strengman; Annemarie A. Van Elburg; Alice Bruson; Maurizio Clementi; Daniela Degortes; Monica Forzan; Elena Tenconi; Elisa Docampo; Georgia Escaramis; Susana Jiménez-Múrcia; Jolanta Lissowska; Andrzej Rajewski -; Neonila Szeszenia-Da¸browska; Agnieszka Slopien; Joanna Wiktoria Hauser; Leila J. Karhunen; Ingrid M. Meulenbelt; Pieternella Eline Slagboom; Alfonso Tortorella; Mario Maj; George V.Z. Dedoussis; Dimitris G. Dikeos; Fragiskos Gonidakis; K. Tziouvas; Artemis Tsitsika; Hana Papezová; Lenka Šlachtová; D. Martásková; James Lowery Kennedy; Robert Daniel Levitan; Zeynep Yilmaz; Julia Huemer; Doris Koubek; Elisabeth Merl; Gudrun Wagner; Paul Lichtenstein; Gerome Breen; Sarah Louise Cohen-Woods; Anne E. Farmer; Peter McGuffin; Sven Cichon; Ina Giegling; Stefan Herms; Dan Rujescu; Stefan Schreiber; Heinz Erich Wichmann; Christian Dina; Robert S. Sladek; Giovanni Gambaro; Nicole Soranzo; Antonio F. Julià; Sara Marsal; Raquel Rabionet; Valérie Gaborieau; Danielle M. Dick; Aarno V. Palotie; Samuli O. Ripatti; Elisabeth E. Widén; Ole Andreas Andreassen; Thomas Espeseth; Astri Johansen Lundervold; Ivar R. Reinvang; Vidar Martin Steen; Stéphanie Le Hellard; Morten Mattingsdal; Ioanna Ntalla; Vladimir Bencko; Lenka Foretová; Vladimír Janout; Marie Navrátilová; Steven J. Gallinger; Dalila Pinto; Stephen W. Scherer; Harald Nikolaus Aschauer; Laura Carlberg; Alexandra Schosser; Lars S. Alfredsson; Bo Ding; Lars G. Klareskog; Leonid Padyukov; Chris I. Finan; Gursharan K. Kalsi; Marion E. Roberts; Jeffrey C. Barrett; Xavier Estivill; Anke Hinney; Patrick F. Sullivan; Eleftheria Zeggini; Cynthia Marie Bulik; Harry A. Brandt; Steve F. Crawford; Scott J. Crow; Manfred Maximilian Fichter; Katherine Ann Halmi.; Craig L. Johnson; Allan S. Kaplan; Maria C. la Via; James E. Mitchell; Michael A. Strober; Alessandro Rotondo; Janet Treasure; D. Blake Woodside; Pamela K. Keel; Kelly L. Klump; Lisa Rachelle Lilenfeld; Andrew W. Bergen; Walter H. Kaye; Pierre J. 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.M. Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J. Bhoj, Nora Robinson, Debra J. Abrams, Yun R. Li, Jonathan P. Bradfield, Cecilia E. Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Y. Guo, Haijun Qiu, Frank D. MentchKelly A. Thomas, Rosetta M. Chiavacci, Roger D. Cone, Bingshan Li, Patrick M.A. Sleiman, Håkon H. Håkonarson, Vesna Boraska Perica, Christopher S. Franklin, James A.B. Floyd, Laura Marie Thornton, Laura M. Huckins, Lorraine Southam, Nigel William Rayner, Ioanna Tachmazidou, Ulrike H. Schmidt, Federica Tozzi, Kirsty Kiezebrink, Johannes Hebebrand, Philip A.P.M. Gorwood, Roger A.H. Adan, Martien J.H. Kas, Angela Favaro, Paolo Santonastaso, Fernando Fernánde-Aranda, Mònica Gratacòs, Filip Rybakowski, Monika Paulina 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 Knudsen, Palmiero Monteleone, Andreas F.K. 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 E. Hilliard, Julie K. O'Toole, Jacques Pantel, Jin Peng Szatkiewicz, Stephanie C. Zerwas, Oliver S.P. Davis, Sietske G. Helder, Katharina Bühren, Roland Burghardt, Martina De Zwaan, Karin Maria Egberts, Stefan Ehrlich, Beate M. 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, R. A. Ophoff, Eric Strengman, Annemarie A. Van Elburg, Alice Bruson, Maurizio Clementi, Daniela Degortes, Monica Forzan, Elena Tenconi, Elisa Docampo, Georgia Escaramis, Susana Jiménez-Múrcia, Jolanta Lissowska, Andrzej Rajewski -, Neonila Szeszenia-Da¸browska, Agnieszka Slopien, Joanna Wiktoria Hauser, Leila J. Karhunen, Ingrid M. Meulenbelt, Pieternella Eline Slagboom, Alfonso Tortorella, Mario Maj, George V.Z. Dedoussis, Dimitris G. Dikeos, Fragiskos Gonidakis, K. Tziouvas, Artemis Tsitsika, Hana Papezová, Lenka Šlachtová, D. Martásková, James Lowery Kennedy, Robert Daniel Levitan, Zeynep Yilmaz, Julia Huemer, Doris Koubek, Elisabeth Merl, Gudrun Wagner, Paul Lichtenstein, Gerome Breen, Sarah Louise Cohen-Woods, Anne E. Farmer, Peter McGuffin, Sven Cichon, Ina Giegling, Stefan Herms, Dan Rujescu, Stefan Schreiber, Heinz Erich Wichmann, Christian Dina, Robert S. Sladek, Giovanni Gambaro, Nicole Soranzo, Antonio F. Julià, Sara Marsal, Raquel Rabionet, Valérie Gaborieau, Danielle M. Dick, Aarno V. Palotie, Samuli O. Ripatti, Elisabeth E. Widén, Ole Andreas Andreassen, Thomas Espeseth, Astri Johansen Lundervold, Ivar R. Reinvang, Vidar Martin Steen, Stéphanie Le Hellard, Morten Mattingsdal, Ioanna Ntalla, Vladimir Bencko, Lenka Foretová, Vladimír Janout, Marie Navrátilová, Steven J. Gallinger, Dalila Pinto, Stephen W. Scherer, Harald Nikolaus Aschauer, Laura Carlberg, Alexandra Schosser, Lars S. Alfredsson, Bo Ding, Lars G. Klareskog, Leonid Padyukov, Chris I. Finan, Gursharan K. Kalsi, Marion E. Roberts, Jeffrey C. Barrett, Xavier Estivill, Anke Hinney, Patrick F. Sullivan, Eleftheria Zeggini, Cynthia Marie Bulik, Harry A. Brandt, Steve F. Crawford, Scott J. Crow, Manfred Maximilian Fichter, Katherine Ann Halmi., Craig L. Johnson, Allan S. Kaplan, Maria C. la Via, James E. Mitchell, Michael A. Strober, Alessandro Rotondo, Janet Treasure, D. Blake Woodside, Pamela K. Keel, Kelly L. Klump, Lisa Rachelle Lilenfeld, Andrew W. Bergen, Walter H. Kaye, Pierre J. Magistretti

Flinders University

Research output: Contribution to journal › Article › peer-review

28 Citations (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 × 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.

Original language	English
Article number	3847
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-01674-8
Publication status	Published - 2017

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10.1038/s41598-017-01674-8

Cite this

Li, D., Chang, X., Connolly, J. J. M., Tian, L., Liu, Y., Bhoj, E. J., Robinson, N., Abrams, D. J., 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. J. (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7(1), Article 3847. https://doi.org/10.1038/s41598-017-01674-8

@article{615b56f1e4fc463e9caf9d91da27b33a,

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 × 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.",

author = "Dong Li and Xiao Chang and Connolly, {John J.M.} and Lifeng Tian and Yichuan Liu and Bhoj, {Elizabeth J.} and Nora Robinson and Abrams, {Debra J.} 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 Y. Guo and Haijun Qiu and Mentch, {Frank D.} and Thomas, {Kelly A.} and Chiavacci, {Rosetta M.} and Cone, {Roger D.} and Bingshan Li and Sleiman, {Patrick M.A.} and H{\aa}konarson, {H{\aa}kon H.} and Perica, {Vesna Boraska} and Franklin, {Christopher S.} and Floyd, {James A.B.} and Thornton, {Laura Marie} and Huckins, {Laura M.} and Lorraine Southam and Rayner, {Nigel William} and Ioanna Tachmazidou and Schmidt, {Ulrike H.} and Federica Tozzi and Kirsty Kiezebrink and Johannes Hebebrand and Gorwood, {Philip A.P.M.} and Adan, {Roger A.H.} and Kas, {Martien J.H.} and Angela Favaro and Paolo Santonastaso and Fernando Fern{\'a}nde-Aranda and M{\`o}nica Gratac{\`o}s and Filip Rybakowski and Dmitrzak-Weglarz, {Monika Paulina} 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} and Palmiero Monteleone and Karwautz, {Andreas F.K.} and Berrettini, {Wade H.} and Schork, {Nicholas J.} and Tetsuya Ando and Hidetoshi Inoko and T{\~o}nu 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 Peng} and Zerwas, {Stephanie C.} and Davis, {Oliver S.P.} and Helder, {Sietske G.} and Katharina B{\"u}hren and Roland Burghardt and {De Zwaan}, Martina and Egberts, {Karin Maria} and Stefan Ehrlich and Herpertz-Dahlmann, {Beate M.} 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, {R. 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 Georgia Escaramis and Susana Jim{\'e}nez-M{\'u}rcia and Jolanta Lissowska and {Rajewski -}, Andrzej and Neonila Szeszenia-Da¸browska and Agnieszka Slopien and Hauser, {Joanna Wiktoria} and Karhunen, {Leila J.} and Meulenbelt, {Ingrid M.} and Slagboom, {Pieternella Eline} and Alfonso Tortorella and Mario Maj and Dedoussis, {George V.Z.} and Dikeos, {Dimitris G.} and Fragiskos Gonidakis and K. Tziouvas and Artemis Tsitsika and Hana Papezov{\'a} and Lenka {\v S}lachtov{\'a} and D. Mart{\'a}skov{\'a} and Kennedy, {James Lowery} and Levitan, {Robert Daniel} and Zeynep Yilmaz and Julia Huemer and Doris Koubek and Elisabeth Merl and Gudrun Wagner and Paul Lichtenstein and Gerome Breen and Cohen-Woods, {Sarah Louise} and Farmer, {Anne E.} and Peter McGuffin and Sven Cichon and Ina Giegling and Stefan Herms and Dan Rujescu and Stefan Schreiber and Wichmann, {Heinz Erich} and Christian Dina and Sladek, {Robert S.} and Giovanni Gambaro and Nicole Soranzo and Juli{\`a}, {Antonio F.} and Sara Marsal and Raquel Rabionet and Val{\'e}rie Gaborieau and Dick, {Danielle M.} and Palotie, {Aarno V.} and Ripatti, {Samuli O.} and Wid{\'e}n, {Elisabeth E.} and Andreassen, {Ole Andreas} and Thomas Espeseth and Lundervold, {Astri Johansen} and Reinvang, {Ivar R.} and Steen, {Vidar Martin} and {Le Hellard}, St{\'e}phanie and Morten Mattingsdal and Ioanna Ntalla and Vladimir Bencko and Lenka Foretov{\'a} and Vladim{\'i}r Janout and Marie Navr{\'a}tilov{\'a} and Gallinger, {Steven J.} and Dalila Pinto and Scherer, {Stephen W.} and Aschauer, {Harald Nikolaus} and Laura Carlberg and Alexandra Schosser and Alfredsson, {Lars S.} and Bo Ding and Klareskog, {Lars G.} and Leonid Padyukov and Finan, {Chris I.} and Kalsi, {Gursharan K.} and Roberts, {Marion E.} and Barrett, {Jeffrey C.} and Xavier Estivill and Anke Hinney and Sullivan, {Patrick F.} and Eleftheria Zeggini and Bulik, {Cynthia Marie} and Brandt, {Harry A.} and Crawford, {Steve F.} and Crow, {Scott J.} and Fichter, {Manfred Maximilian} and Halmi., {Katherine Ann} and Johnson, {Craig L.} and Kaplan, {Allan S.} and {la Via}, {Maria C.} and Mitchell, {James E.} and Strober, {Michael A.} and Alessandro Rotondo and Janet Treasure and Woodside, {D. Blake} and Keel, {Pamela K.} and Klump, {Kelly L.} and Lilenfeld, {Lisa Rachelle} and Bergen, {Andrew W.} and Kaye, {Walter H.} and Magistretti, {Pierre J.}",

year = "2017",

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

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Li, D, Chang, X, Connolly, JJM, Tian, L, Liu, Y, Bhoj, EJ, Robinson, N, Abrams, DJ, 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, RD, Li, B, Sleiman, PMA, Håkonarson, HH, Perica, VB, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Schmidt, UH, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, PAPM, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernánde-Aranda, F, Gratacòs, M, Rybakowski, F, Dmitrzak-Weglarz, MP, Kaprio, J, Keski-Rahkonen, A, Raevuori-Helkamaa, A, Furth, EFV, Slof-Opt Landt, MCT, Hudson, JI, Reichborn-Kjennerud, T, Knudsen, GP, Monteleone, P, Karwautz, AFK, 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, SC, Davis, OSP, Helder, SG, Bühren, K, Burghardt, R, De Zwaan, M, Egberts, KM, Ehrlich, S, Herpertz-Dahlmann, BM, 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, Escaramis, G, Jiménez-Múrcia, S, Lissowska, J, Rajewski -, A, Szeszenia-Da¸browska, N, Slopien, A, Hauser, JW, Karhunen, LJ, Meulenbelt, IM, Slagboom, PE, Tortorella, A, Maj, M, Dedoussis, GVZ, Dikeos, DG, Gonidakis, F, Tziouvas, K, Tsitsika, A, Papezová, H, Šlachtová, L, Martásková, D, Kennedy, JL, Levitan, RD, Yilmaz, Z, Huemer, J, Koubek, D, Merl, E, Wagner, G, Lichtenstein, P, Breen, G, Cohen-Woods, SL, Farmer, AE, McGuffin, P, Cichon, S, Giegling, I, Herms, S, Rujescu, D, Schreiber, S, Wichmann, HE, Dina, C, Sladek, RS, Gambaro, G, Soranzo, N, Julià, AF, Marsal, S, Rabionet, R, Gaborieau, V, Dick, DM, Palotie, AV, Ripatti, SO, Widén, EE, Andreassen, OA, Espeseth, T, Lundervold, AJ, Reinvang, IR, Steen, VM, Le Hellard, S, Mattingsdal, M, Ntalla, I, Bencko, V, Foretová, L, Janout, V, Navrátilová, M, Gallinger, SJ, Pinto, D, Scherer, SW, Aschauer, HN, Carlberg, L, Schosser, A, Alfredsson, LS, Ding, B, Klareskog, LG, Padyukov, L, Finan, CI, Kalsi, GK, Roberts, ME, Barrett, JC, Estivill, X, Hinney, A, Sullivan, PF, Zeggini, E, Bulik, CM, Brandt, HA, Crawford, SF, Crow, SJ, Fichter, MM, Halmi., KA, Johnson, CL, Kaplan, AS, la Via, MC, Mitchell, JE, Strober, MA, Rotondo, A, Treasure, J, Woodside, DB, Keel, PK, Klump, KL, Lilenfeld, LR, Bergen, AW, Kaye, WH & Magistretti, PJ 2017, 'A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling', Scientific Reports, vol. 7, no. 1, 3847. 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.M.

AU - Tian, Lifeng

AU - Liu, Yichuan

AU - Bhoj, Elizabeth J.

AU - Robinson, Nora

AU - Abrams, Debra J.

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, Y.

AU - Qiu, Haijun

AU - Mentch, Frank D.

AU - Thomas, Kelly A.

AU - Chiavacci, Rosetta M.

AU - Cone, Roger D.

AU - Li, Bingshan

AU - Sleiman, Patrick M.A.

AU - Håkonarson, Håkon H.

AU - Perica, Vesna Boraska

AU - Franklin, Christopher S.

AU - Floyd, James A.B.

AU - Thornton, Laura Marie

AU - Huckins, Laura M.

AU - Southam, Lorraine

AU - Rayner, Nigel William

AU - Tachmazidou, Ioanna

AU - Schmidt, Ulrike H.

AU - Tozzi, Federica

AU - Kiezebrink, Kirsty

AU - Hebebrand, Johannes

AU - Gorwood, Philip A.P.M.

AU - Adan, Roger A.H.

AU - Kas, Martien J.H.

AU - Favaro, Angela

AU - Santonastaso, Paolo

AU - Fernánde-Aranda, Fernando

AU - Gratacòs, Mònica

AU - Rybakowski, Filip

AU - Dmitrzak-Weglarz, Monika Paulina

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

AU - Monteleone, Palmiero

AU - Karwautz, Andreas F.K.

AU - Berrettini, Wade H.

AU - Schork, Nicholas J.

AU - Ando, Tetsuya

AU - Inoko, Hidetoshi

AU - Esko, Tõnu

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 Peng

AU - Zerwas, Stephanie C.

AU - Davis, Oliver S.P.

AU - Helder, Sietske G.

AU - Bühren, Katharina

AU - Burghardt, Roland

AU - De Zwaan, Martina

AU - Egberts, Karin Maria

AU - Ehrlich, Stefan

AU - Herpertz-Dahlmann, Beate M.

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, R. 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 - Escaramis, Georgia

AU - Jiménez-Múrcia, Susana

AU - Lissowska, Jolanta

AU - Rajewski -, Andrzej

AU - Szeszenia-Da¸browska, Neonila

AU - Slopien, Agnieszka

AU - Hauser, Joanna Wiktoria

AU - Karhunen, Leila J.

AU - Meulenbelt, Ingrid M.

AU - Slagboom, Pieternella Eline

AU - Tortorella, Alfonso

AU - Maj, Mario

AU - Dedoussis, George V.Z.

AU - Dikeos, Dimitris G.

AU - Gonidakis, Fragiskos

AU - Tziouvas, K.

AU - Tsitsika, Artemis

AU - Papezová, Hana

AU - Šlachtová, Lenka

AU - Martásková, D.

AU - Kennedy, James Lowery

AU - Levitan, Robert Daniel

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 Louise

AU - Farmer, Anne E.

AU - McGuffin, Peter

AU - Cichon, Sven

AU - Giegling, Ina

AU - Herms, Stefan

AU - Rujescu, Dan

AU - Schreiber, Stefan

AU - Wichmann, Heinz Erich

AU - Dina, Christian

AU - Sladek, Robert S.

AU - Gambaro, Giovanni

AU - Soranzo, Nicole

AU - Julià, Antonio F.

AU - Marsal, Sara

AU - Rabionet, Raquel

AU - Gaborieau, Valérie

AU - Dick, Danielle M.

AU - Palotie, Aarno V.

AU - Ripatti, Samuli O.

AU - Widén, Elisabeth E.

AU - Andreassen, Ole Andreas

AU - Espeseth, Thomas

AU - Lundervold, Astri Johansen

AU - Reinvang, Ivar R.

AU - Steen, Vidar Martin

AU - Le Hellard, Stéphanie

AU - Mattingsdal, Morten

AU - Ntalla, Ioanna

AU - Bencko, Vladimir

AU - Foretová, Lenka

AU - Janout, Vladimír

AU - Navrátilová, Marie

AU - Gallinger, Steven J.

AU - Pinto, Dalila

AU - Scherer, Stephen W.

AU - Aschauer, Harald Nikolaus

AU - Carlberg, Laura

AU - Schosser, Alexandra

AU - Alfredsson, Lars S.

AU - Ding, Bo

AU - Klareskog, Lars G.

AU - Padyukov, Leonid

AU - Finan, Chris I.

AU - Kalsi, Gursharan K.

AU - Roberts, Marion E.

AU - Barrett, Jeffrey C.

AU - Estivill, Xavier

AU - Hinney, Anke

AU - Sullivan, Patrick F.

AU - Zeggini, Eleftheria

AU - Bulik, Cynthia Marie

AU - Brandt, Harry A.

AU - Crawford, Steve F.

AU - Crow, Scott J.

AU - Fichter, Manfred Maximilian

AU - Halmi., Katherine Ann

AU - Johnson, Craig L.

AU - Kaplan, Allan S.

AU - la Via, Maria C.

AU - Mitchell, James E.

AU - Strober, Michael A.

AU - Rotondo, Alessandro

AU - Treasure, Janet

AU - Woodside, D. Blake

AU - Keel, Pamela K.

AU - Klump, Kelly L.

AU - Lilenfeld, Lisa Rachelle

AU - Bergen, Andrew W.

AU - Kaye, Walter H.

AU - Magistretti, Pierre J.

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 × 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 × 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.

UR - http://www.scopus.com/inward/record.url?scp=85021082843&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-01674-8

DO - 10.1038/s41598-017-01674-8

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 3847

ER -

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

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