Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

Laramie Duncan; Zeynep Yilmaz; Helena Gaspar; Raymond Walters; Jackie Goldstein; Verneri Anttila; Brendan Bulik-Sullivan; Stephan Ripke; Laura Thornton; Anke Hinney; Mark Daly; Patrick F. Sullivan; Eleftheria Zeggini; Gerome Breen; Cynthia M. Bulik; Héléna Gaspar; Roger Adan; Lars Alfredsson; Tetsuya Ando; Ole Andreassen; Harald Aschauer; Jessica Baker; Jeffrey Barrett; Vladimir Bencko; Andrew Bergen; Wade Berrettini; Andreas Birgegård; Claudette Boni; Vesna Boraska Perica; Harry Brandt; Roland Burghardt; Laura Carlberg; Matteo Cassina; Carolyn Cesta; Sven Cichon; Maurizio Clementi; Sarah Cohen-Woods; Joni Coleman; Roger Cone; Philippe Courtet; Steven Crawford; Scott Crow; Jim Crowley; Unna Danner; Oliver Davis; Martina de Zwaan; George Dedoussis; Daniela Degortes; Janiece DeSocio; Dick N. Danielle; Dimitris Dikeos; Christian Dina; Bo Ding; Monika Dmitrzak-Weglarz; Elisa Docampo; Karin Egberts; Stefan Ehrlich; Geòrgia Escaramís; Tõnu Esko; Thomas Espeseth; Xavier Estivill; Angela Favaro; Fernando Fernández-Aranda; Manfred Fichter; Chris Finan; Krista Fischer; James Floyd; Manuel Föcker; Lenka Foretova; Monica Forzan; Caroline Fox; Christopher Franklin; Valerie Gaborieau; Steven Gallinger; Giovanni Gambaro; Ina Giegling; Fragiskos Gonidakis; Philip Gorwood; Monica Gratacos; Sébastien Guillaume; Yiran Guo; Hakon Hakonarson; Katherine Halmi; Rebecca Harrison; Konstantinos Hatzikotoulas; Joanna Hauser; Johannes Hebebrand; Sietske Helder; Judith Hendriks; Stefan Herms; Beate Herpertz-Dahlmann; Wolfgang Herzog; Christopher Hilliard; Laura Huckins; James Hudson; Julia Huemer; Hartmut Imgart; Hidetoshi Inoko; Sigrid Jall; Stephane Jamain; Vladimir Janout; Susana Jiménez-Murcia; Craig Johnson; Jenny Jordan; Antonio Julià; Anders Juréus; Gursharan Kalsi; Allan Kaplan; Jaakko Kaprio; Leila Karhunen; Andreas Karwautz; Martien Kas; Walter Kaye; Martin Kennedy; James Kennedy; Anna Keski-Rahkonen; Kirsty Kiezebrink; Youl Ri Kim; Lars Klareskog; Kelly Klump; Gun Peggy Knudsen; Bobby Koeleman; Doris Koubek; Maria La Via; Mikael Landén; Stephanie Le Hellard; Marion Leboyer; Robert Levitan; Dong Li; Paul Lichtenstein; Lisa Lilenfeld; Jolanta Lissowska; Astri Lundervold; Pierre Magistretti; Mario Maj; Katrin Mannik; Sara Marsal; Debora Kaminska; Nicholas Martin; Morten Mattingsdal; Sara McDevitt; Peter McGuffin; Elisabeth Merl; Andres Metspalu; Ingrid Meulenbelt; Nadia Micali; Karen Mitchell; Palmiero Monteleone; Alessio Maria Monteleone; Grant Montgomery; Preben Mortensen; Melissa Munn-Chernoff; Timo Müller; Benedetta Nacmias; Marie Navratilova; Ida Nilsson; Claes Norring; Ioanna Ntalla; Roel Ophoff; Julie O’Toole; Aarno Palotie; Jacques Pantel; Hana Papezova; Richard Parker; Dalila Pinto; Raquel Rabionet; Anu Raevuori; Andrzej Rajewski; Nicolas Ramoz; N. William Rayner; Ted Reichborn-Kjennerud; Valdo Ricca; Samuli Ripatti; Franziska Ritschel; Marion Roberts; Alessandro Rotondo; Dan Rujescu; Filip Rybakowski; Paolo Santonastaso; André Scherag; Stephen Scherer; Ulrike Schmidt; Nicholas Schork; Alexandra Schosser; Laura Scott; Jochen Seitz; Lenka Slachtova; Robert Sladek; P. Eline Slagboom; Margarita Slof-Op ’t Landt; Agnieszka Slopien; Tosha Smith; Nicole Soranzo; Sandro Sorbi; Lorraine Southam; Vidar Steen; Eric Strengman; Michael Strober; Jin Szatkiewicz; Neonila Szeszenia-Dabrowska; Ioanna Tachmazidou; Elena Tenconi; Alfonso Tortorella; Federica Tozzi; Janet Treasure; Matthias Tschöp; Artemis Tsitsika; Konstantinos Tziouvas; Annemarie van Elburg; Eric van Furth; Tracey Wade; Gudrun Wagner; Esther Walton; Hunna Watson; H. Erich Wichmann; Elisabeth Widen; Blake Woodside; Jack Yanovski; Shuyang Yao; Stephanie Zerwas; Stephan Zipfel

doi:10.1176/appi.ajp.2017.16121402

Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

Laramie Duncan, Zeynep Yilmaz, Helena Gaspar, Raymond Walters, Jackie Goldstein, Verneri Anttila, Brendan Bulik-Sullivan, Stephan Ripke, Laura Thornton, Anke Hinney, Mark Daly, Patrick F. Sullivan, Eleftheria Zeggini, Gerome Breen, Cynthia M. Bulik, Héléna Gaspar, Roger Adan, Lars Alfredsson, Tetsuya Ando, Ole AndreassenHarald Aschauer, Jessica Baker, Jeffrey Barrett, Vladimir Bencko, Andrew Bergen, Wade Berrettini, Andreas Birgegård, Claudette Boni, Vesna Boraska Perica, Harry Brandt, Roland Burghardt, Laura Carlberg, Matteo Cassina, Carolyn Cesta, Sven Cichon, Maurizio Clementi, Sarah Cohen-Woods, Joni Coleman, Roger Cone, Philippe Courtet, Steven Crawford, Scott Crow, Jim Crowley, Unna Danner, Oliver Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece DeSocio, Dick N. Danielle, Dimitris Dikeos, Christian Dina, Bo Ding, Monika Dmitrzak-Weglarz, Elisa Docampo, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Thomas Espeseth, Xavier Estivill, Angela Favaro, Fernando Fernández-Aranda, Manfred Fichter, Chris Finan, Krista Fischer, James Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Caroline Fox, Christopher Franklin, Valerie Gaborieau, Steven Gallinger, Giovanni Gambaro, Ina Giegling, Fragiskos Gonidakis, Philip Gorwood, Monica Gratacos, Sébastien Guillaume, Yiran Guo, Hakon Hakonarson, Katherine Halmi, Rebecca Harrison, Konstantinos Hatzikotoulas, Joanna Hauser, Johannes Hebebrand, Sietske Helder, Judith Hendriks, Stefan Herms, Beate Herpertz-Dahlmann, Wolfgang Herzog, Christopher Hilliard, Laura Huckins, James Hudson, Julia Huemer, Hartmut Imgart, Hidetoshi Inoko, Sigrid Jall, Stephane Jamain, Vladimir Janout, Susana Jiménez-Murcia, Craig Johnson, Jenny Jordan, Antonio Julià, Anders Juréus, Gursharan Kalsi, Allan Kaplan, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien Kas, Walter Kaye, Martin Kennedy, James Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl Ri Kim, Lars Klareskog, Kelly Klump, Gun Peggy Knudsen, Bobby Koeleman, Doris Koubek, Maria La Via, Mikael Landén, Stephanie Le Hellard, Marion Leboyer, Robert Levitan, Dong Li, Paul Lichtenstein, Lisa Lilenfeld, Jolanta Lissowska, Astri Lundervold, Pierre Magistretti, Mario Maj, Katrin Mannik, Sara Marsal, Debora Kaminska, Nicholas Martin, Morten Mattingsdal, Sara McDevitt, Peter McGuffin, Elisabeth Merl, Andres Metspalu, Ingrid Meulenbelt, Nadia Micali, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Grant Montgomery, Preben Mortensen, Melissa Munn-Chernoff, Timo Müller, Benedetta Nacmias, Marie Navratilova, Ida Nilsson, Claes Norring, Ioanna Ntalla, Roel Ophoff, Julie O’Toole, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, Dalila Pinto, Raquel Rabionet, Anu Raevuori, Andrzej Rajewski, Nicolas Ramoz, N. William Rayner, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Alessandro Rotondo, Dan Rujescu, Filip Rybakowski, Paolo Santonastaso, André Scherag, Stephen Scherer, Ulrike Schmidt, Nicholas Schork, Alexandra Schosser, Laura Scott, Jochen Seitz, Lenka Slachtova, Robert Sladek, P. Eline Slagboom, Margarita Slof-Op ’t Landt, Agnieszka Slopien, Tosha Smith, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar Steen, Eric Strengman, Michael Strober, Jin Szatkiewicz, Neonila Szeszenia-Dabrowska, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Matthias Tschöp, Artemis Tsitsika, Konstantinos Tziouvas, Annemarie van Elburg, Eric van Furth, Tracey Wade, Gudrun Wagner, Esther Walton, Hunna Watson, H. Erich Wichmann, Elisabeth Widen, Blake Woodside, Jack Yanovski, Shuyang Yao, Stephanie Zerwas, Stephan Zipfel

Department of Psychology

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

350 Citations (SciVal)

Abstract

Objective: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method: Following uniformquality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3, 495 anorexia nervosa cases and 10, 982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2 SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results: Results were obtained for 10, 641, 224 SNPs and insertion-deletion variants with minor allele frequencies.>1% and imputation quality scores >0.6. The h2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genomewide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Original language	English
Pages (from-to)	850-858
Number of pages	9
Journal	American Journal of Psychiatry
Volume	174
Issue number	9
Early online date	12 May 2017
DOIs	https://doi.org/10.1176/appi.ajp.2017.16121402
Publication status	Published - 1 Sept 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1176/appi.ajp.2017.16121402

Cite this

Duncan, L., Yilmaz, Z., Gaspar, H., Walters, R., Goldstein, J., Anttila, V., Bulik-Sullivan, B., Ripke, S., Thornton, L., Hinney, A., Daly, M., Sullivan, P. F., Zeggini, E., Breen, G., Bulik, C. M., Gaspar, H., Adan, R., Alfredsson, L., Ando, T., ... Zipfel, S. (2017). Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. American Journal of Psychiatry, 174(9), 850-858. https://doi.org/10.1176/appi.ajp.2017.16121402

Duncan, L, Yilmaz, Z, Gaspar, H, Walters, R, Goldstein, J, Anttila, V, Bulik-Sullivan, B, Ripke, S, Thornton, L, Hinney, A, Daly, M, Sullivan, PF, Zeggini, E, Breen, G, Bulik, CM, Gaspar, H, Adan, R, Alfredsson, L, Ando, T, Andreassen, O, Aschauer, H, Baker, J, Barrett, J, Bencko, V, Bergen, A, Berrettini, W, Birgegård, A, Boni, C, Perica, VB, Brandt, H, Burghardt, R, Carlberg, L, Cassina, M, Cesta, C, Cichon, S, Clementi, M, Cohen-Woods, S, Coleman, J, Cone, R, Courtet, P, Crawford, S, Crow, S, Crowley, J, Danner, U, Davis, O, de Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, J, Danielle, DN, Dikeos, D, Dina, C, Ding, B, Dmitrzak-Weglarz, M, Docampo, E, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Espeseth, T, Estivill, X, Favaro, A, Fernández-Aranda, F, Fichter, M, Finan, C, Fischer, K, Floyd, J, Föcker, M, Foretova, L, Forzan, M, Fox, C, Franklin, C, Gaborieau, V, Gallinger, S, Gambaro, G, Giegling, I, Gonidakis, F, Gorwood, P, Gratacos, M, Guillaume, S, Guo, Y, Hakonarson, H, Halmi, K, Harrison, R, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, S, Hendriks, J, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Hilliard, C, Huckins, L, Hudson, J, Huemer, J, Imgart, H, Inoko, H, Jall, S, Jamain, S, Janout, V, Jiménez-Murcia, S, Johnson, C, Jordan, J, Julià, A, Juréus, A, Kalsi, G, Kaplan, A, Kaprio, J, Karhunen, L, Karwautz, A, Kas, M, Kaye, W, Kennedy, M, Kennedy, J, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klareskog, L, Klump, K, Knudsen, GP, Koeleman, B, Koubek, D, La Via, M, Landén, M, Le Hellard, S, Leboyer, M, Levitan, R, Li, D, Lichtenstein, P, Lilenfeld, L, Lissowska, J, Lundervold, A, Magistretti, P, Maj, M, Mannik, K, Marsal, S, Kaminska, D, Martin, N, Mattingsdal, M, McDevitt, S, McGuffin, P, Merl, E, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, P, Monteleone, AM, Montgomery, G, Mortensen, P, Munn-Chernoff, M, Müller, T, Nacmias, B, Navratilova, M, Nilsson, I, Norring, C, Ntalla, I, Ophoff, R, O’Toole, J, Palotie, A, Pantel, J, Papezova, H, Parker, R, Pinto, D, Rabionet, R, Raevuori, A, Rajewski, A, Ramoz, N, William Rayner, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, S, Schmidt, U, Schork, N, Schosser, A, Scott, L, Seitz, J, Slachtova, L, Sladek, R, Eline Slagboom, P, Slof-Op ’t Landt, M, Slopien, A, Smith, T, Soranzo, N, Sorbi, S, Southam, L, Steen, V, Strengman, E, Strober, M, Szatkiewicz, J, Szeszenia-Dabrowska, N, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tschöp, M, Tsitsika, A, Tziouvas, K, van Elburg, A, van Furth, E, Wade, T, Wagner, G, Walton, E, Watson, H, Wichmann, HE, Widen, E, Woodside, B, Yanovski, J, Yao, S, Zerwas, S & Zipfel, S 2017, 'Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa', American Journal of Psychiatry, vol. 174, no. 9, pp. 850-858. https://doi.org/10.1176/appi.ajp.2017.16121402

@article{96d81c4d8e2f4f42944849179f5e093b,

title = "Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa",

abstract = "Objective: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method: Following uniformquality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3, 495 anorexia nervosa cases and 10, 982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2 SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results: Results were obtained for 10, 641, 224 SNPs and insertion-deletion variants with minor allele frequencies.>1% and imputation quality scores >0.6. The h2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genomewide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.",

author = "Laramie Duncan and Zeynep Yilmaz and Helena Gaspar and Raymond Walters and Jackie Goldstein and Verneri Anttila and Brendan Bulik-Sullivan and Stephan Ripke and Laura Thornton and Anke Hinney and Mark Daly and Sullivan, {Patrick F.} and Eleftheria Zeggini and Gerome Breen and Bulik, {Cynthia M.} and H{\'e}l{\'e}na Gaspar and Roger Adan and Lars Alfredsson and Tetsuya Ando and Ole Andreassen and Harald Aschauer and Jessica Baker and Jeffrey Barrett and Vladimir Bencko and Andrew Bergen and Wade Berrettini and Andreas Birgeg{\aa}rd and Claudette Boni and Perica, {Vesna Boraska} and Harry Brandt and Roland Burghardt and Laura Carlberg and Matteo Cassina and Carolyn Cesta and Sven Cichon and Maurizio Clementi and Sarah Cohen-Woods and Joni Coleman and Roger Cone and Philippe Courtet and Steven Crawford and Scott Crow and Jim Crowley and Unna Danner and Oliver Davis and {de Zwaan}, Martina and George Dedoussis and Daniela Degortes and Janiece DeSocio and Danielle, {Dick N.} and Dimitris Dikeos and Christian Dina and Bo Ding and Monika Dmitrzak-Weglarz and Elisa Docampo and Karin Egberts and Stefan Ehrlich and Ge{\`o}rgia Escaram{\'i}s and T{\~o}nu Esko and Thomas Espeseth and Xavier Estivill and Angela Favaro and Fernando Fern{\'a}ndez-Aranda and Manfred Fichter and Chris Finan and Krista Fischer and James Floyd and Manuel F{\"o}cker and Lenka Foretova and Monica Forzan and Caroline Fox and Christopher Franklin and Valerie Gaborieau and Steven Gallinger and Giovanni Gambaro and Ina Giegling and Fragiskos Gonidakis and Philip Gorwood and Monica Gratacos and S{\'e}bastien Guillaume and Yiran Guo and Hakon Hakonarson and Katherine Halmi and Rebecca Harrison and Konstantinos Hatzikotoulas and Joanna Hauser and Johannes Hebebrand and Sietske Helder and Judith Hendriks and Stefan Herms and Beate Herpertz-Dahlmann and Wolfgang Herzog and Christopher Hilliard and Laura Huckins and James Hudson and Julia Huemer and Hartmut Imgart and Hidetoshi Inoko and Sigrid Jall and Stephane Jamain and Vladimir Janout and Susana Jim{\'e}nez-Murcia and Craig Johnson and Jenny Jordan and Antonio Juli{\`a} and Anders Jur{\'e}us and Gursharan Kalsi and Allan Kaplan and Jaakko Kaprio and Leila Karhunen and Andreas Karwautz and Martien Kas and Walter Kaye and Martin Kennedy and James Kennedy and Anna Keski-Rahkonen and Kirsty Kiezebrink and Kim, {Youl Ri} and Lars Klareskog and Kelly Klump and Knudsen, {Gun Peggy} and Bobby Koeleman and Doris Koubek and {La Via}, Maria and Mikael Land{\'e}n and {Le Hellard}, Stephanie and Marion Leboyer and Robert Levitan and Dong Li and Paul Lichtenstein and Lisa Lilenfeld and Jolanta Lissowska and Astri Lundervold and Pierre Magistretti and Mario Maj and Katrin Mannik and Sara Marsal and Debora Kaminska and Nicholas Martin and Morten Mattingsdal and Sara McDevitt and Peter McGuffin and Elisabeth Merl and Andres Metspalu and Ingrid Meulenbelt and Nadia Micali and Karen Mitchell and Palmiero Monteleone and Monteleone, {Alessio Maria} and Grant Montgomery and Preben Mortensen and Melissa Munn-Chernoff and Timo M{\"u}ller and Benedetta Nacmias and Marie Navratilova and Ida Nilsson and Claes Norring and Ioanna Ntalla and Roel Ophoff and Julie O{\textquoteright}Toole and Aarno Palotie and Jacques Pantel and Hana Papezova and Richard Parker and Dalila Pinto and Raquel Rabionet and Anu Raevuori and Andrzej Rajewski and Nicolas Ramoz and {William Rayner}, N. and Ted Reichborn-Kjennerud and Valdo Ricca and Samuli Ripatti and Franziska Ritschel and Marion Roberts and Alessandro Rotondo and Dan Rujescu and Filip Rybakowski and Paolo Santonastaso and Andr{\'e} Scherag and Stephen Scherer and Ulrike Schmidt and Nicholas Schork and Alexandra Schosser and Laura Scott and Jochen Seitz and Lenka Slachtova and Robert Sladek and {Eline Slagboom}, P. and {Slof-Op {\textquoteright}t Landt}, Margarita and Agnieszka Slopien and Tosha Smith and Nicole Soranzo and Sandro Sorbi and Lorraine Southam and Vidar Steen and Eric Strengman and Michael Strober and Jin Szatkiewicz and Neonila Szeszenia-Dabrowska and Ioanna Tachmazidou and Elena Tenconi and Alfonso Tortorella and Federica Tozzi and Janet Treasure and Matthias Tsch{\"o}p and Artemis Tsitsika and Konstantinos Tziouvas and {van Elburg}, Annemarie and {van Furth}, Eric and Tracey Wade and Gudrun Wagner and Esther Walton and Hunna Watson and Wichmann, {H. Erich} and Elisabeth Widen and Blake Woodside and Jack Yanovski and Shuyang Yao and Stephanie Zerwas and Stephan Zipfel",

year = "2017",

month = sep,

day = "1",

doi = "10.1176/appi.ajp.2017.16121402",

language = "English",

volume = "174",

pages = "850--858",

journal = "American Journal of Psychiatry",

issn = "0002-953X",

publisher = "American Psychiatric Association",

number = "9",

}

TY - JOUR

T1 - Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

AU - Duncan, Laramie

AU - Yilmaz, Zeynep

AU - Gaspar, Helena

AU - Walters, Raymond

AU - Goldstein, Jackie

AU - Anttila, Verneri

AU - Bulik-Sullivan, Brendan

AU - Ripke, Stephan

AU - Thornton, Laura

AU - Hinney, Anke

AU - Daly, Mark

AU - Sullivan, Patrick F.

AU - Zeggini, Eleftheria

AU - Breen, Gerome

AU - Bulik, Cynthia M.

AU - Gaspar, Héléna

AU - Adan, Roger

AU - Alfredsson, Lars

AU - Ando, Tetsuya

AU - Andreassen, Ole

AU - Aschauer, Harald

AU - Baker, Jessica

AU - Barrett, Jeffrey

AU - Bencko, Vladimir

AU - Bergen, Andrew

AU - Berrettini, Wade

AU - Birgegård, Andreas

AU - Boni, Claudette

AU - Perica, Vesna Boraska

AU - Brandt, Harry

AU - Burghardt, Roland

AU - Carlberg, Laura

AU - Cassina, Matteo

AU - Cesta, Carolyn

AU - Cichon, Sven

AU - Clementi, Maurizio

AU - Cohen-Woods, Sarah

AU - Coleman, Joni

AU - Cone, Roger

AU - Courtet, Philippe

AU - Crawford, Steven

AU - Crow, Scott

AU - Crowley, Jim

AU - Danner, Unna

AU - Davis, Oliver

AU - de Zwaan, Martina

AU - Dedoussis, George

AU - Degortes, Daniela

AU - DeSocio, Janiece

AU - Danielle, Dick N.

AU - Dikeos, Dimitris

AU - Dina, Christian

AU - Ding, Bo

AU - Dmitrzak-Weglarz, Monika

AU - Docampo, Elisa

AU - Egberts, Karin

AU - Ehrlich, Stefan

AU - Escaramís, Geòrgia

AU - Esko, Tõnu

AU - Espeseth, Thomas

AU - Estivill, Xavier

AU - Favaro, Angela

AU - Fernández-Aranda, Fernando

AU - Fichter, Manfred

AU - Finan, Chris

AU - Fischer, Krista

AU - Floyd, James

AU - Föcker, Manuel

AU - Foretova, Lenka

AU - Forzan, Monica

AU - Fox, Caroline

AU - Franklin, Christopher

AU - Gaborieau, Valerie

AU - Gallinger, Steven

AU - Gambaro, Giovanni

AU - Giegling, Ina

AU - Gonidakis, Fragiskos

AU - Gorwood, Philip

AU - Gratacos, Monica

AU - Guillaume, Sébastien

AU - Guo, Yiran

AU - Hakonarson, Hakon

AU - Halmi, Katherine

AU - Harrison, Rebecca

AU - Hatzikotoulas, Konstantinos

AU - Hauser, Joanna

AU - Hebebrand, Johannes

AU - Helder, Sietske

AU - Hendriks, Judith

AU - Herms, Stefan

AU - Herpertz-Dahlmann, Beate

AU - Herzog, Wolfgang

AU - Hilliard, Christopher

AU - Huckins, Laura

AU - Hudson, James

AU - Huemer, Julia

AU - Imgart, Hartmut

AU - Inoko, Hidetoshi

AU - Jall, Sigrid

AU - Jamain, Stephane

AU - Janout, Vladimir

AU - Jiménez-Murcia, Susana

AU - Johnson, Craig

AU - Jordan, Jenny

AU - Julià, Antonio

AU - Juréus, Anders

AU - Kalsi, Gursharan

AU - Kaplan, Allan

AU - Kaprio, Jaakko

AU - Karhunen, Leila

AU - Karwautz, Andreas

AU - Kas, Martien

AU - Kaye, Walter

AU - Kennedy, Martin

AU - Kennedy, James

AU - Keski-Rahkonen, Anna

AU - Kiezebrink, Kirsty

AU - Kim, Youl Ri

AU - Klareskog, Lars

AU - Klump, Kelly

AU - Knudsen, Gun Peggy

AU - Koeleman, Bobby

AU - Koubek, Doris

AU - La Via, Maria

AU - Landén, Mikael

AU - Le Hellard, Stephanie

AU - Leboyer, Marion

AU - Levitan, Robert

AU - Li, Dong

AU - Lichtenstein, Paul

AU - Lilenfeld, Lisa

AU - Lissowska, Jolanta

AU - Lundervold, Astri

AU - Magistretti, Pierre

AU - Maj, Mario

AU - Mannik, Katrin

AU - Marsal, Sara

AU - Kaminska, Debora

AU - Martin, Nicholas

AU - Mattingsdal, Morten

AU - McDevitt, Sara

AU - McGuffin, Peter

AU - Merl, Elisabeth

AU - Metspalu, Andres

AU - Meulenbelt, Ingrid

AU - Micali, Nadia

AU - Mitchell, Karen

AU - Monteleone, Palmiero

AU - Monteleone, Alessio Maria

AU - Montgomery, Grant

AU - Mortensen, Preben

AU - Munn-Chernoff, Melissa

AU - Müller, Timo

AU - Nacmias, Benedetta

AU - Navratilova, Marie

AU - Nilsson, Ida

AU - Norring, Claes

AU - Ntalla, Ioanna

AU - Ophoff, Roel

AU - O’Toole, Julie

AU - Palotie, Aarno

AU - Pantel, Jacques

AU - Papezova, Hana

AU - Parker, Richard

AU - Pinto, Dalila

AU - Rabionet, Raquel

AU - Raevuori, Anu

AU - Rajewski, Andrzej

AU - Ramoz, Nicolas

AU - William Rayner, N.

AU - Reichborn-Kjennerud, Ted

AU - Ricca, Valdo

AU - Ripatti, Samuli

AU - Ritschel, Franziska

AU - Roberts, Marion

AU - Rotondo, Alessandro

AU - Rujescu, Dan

AU - Rybakowski, Filip

AU - Santonastaso, Paolo

AU - Scherag, André

AU - Scherer, Stephen

AU - Schmidt, Ulrike

AU - Schork, Nicholas

AU - Schosser, Alexandra

AU - Scott, Laura

AU - Seitz, Jochen

AU - Slachtova, Lenka

AU - Sladek, Robert

AU - Eline Slagboom, P.

AU - Slof-Op ’t Landt, Margarita

AU - Slopien, Agnieszka

AU - Smith, Tosha

AU - Soranzo, Nicole

AU - Sorbi, Sandro

AU - Southam, Lorraine

AU - Steen, Vidar

AU - Strengman, Eric

AU - Strober, Michael

AU - Szatkiewicz, Jin

AU - Szeszenia-Dabrowska, Neonila

AU - Tachmazidou, Ioanna

AU - Tenconi, Elena

AU - Tortorella, Alfonso

AU - Tozzi, Federica

AU - Treasure, Janet

AU - Tschöp, Matthias

AU - Tsitsika, Artemis

AU - Tziouvas, Konstantinos

AU - van Elburg, Annemarie

AU - van Furth, Eric

AU - Wade, Tracey

AU - Wagner, Gudrun

AU - Walton, Esther

AU - Watson, Hunna

AU - Wichmann, H. Erich

AU - Widen, Elisabeth

AU - Woodside, Blake

AU - Yanovski, Jack

AU - Yao, Shuyang

AU - Zerwas, Stephanie

AU - Zipfel, Stephan

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Objective: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method: Following uniformquality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3, 495 anorexia nervosa cases and 10, 982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2 SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results: Results were obtained for 10, 641, 224 SNPs and insertion-deletion variants with minor allele frequencies.>1% and imputation quality scores >0.6. The h2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genomewide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

AB - Objective: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method: Following uniformquality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3, 495 anorexia nervosa cases and 10, 982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2 SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. Results: Results were obtained for 10, 641, 224 SNPs and insertion-deletion variants with minor allele frequencies.>1% and imputation quality scores >0.6. The h2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genomewide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

U2 - 10.1176/appi.ajp.2017.16121402

DO - 10.1176/appi.ajp.2017.16121402

M3 - Article

SN - 0002-953X

VL - 174

SP - 850

EP - 858

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

IS - 9

ER -

Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this