Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Hunna J. Watson, Zeynep Yilmaz, Laura M. Thornton, Christopher Hübel, Jonathan R. I. Coleman, Héléna A. Gaspar, Julien Bryois, Anke Hinney, Virpi M. Leppä, Manuel Mattheisen, Sarah E. Medland, Stephan Ripke, Shuyang Yao, Paola Giusti-Rodríguez, Ken B. Hanscombe, Kirstin L. Purves, Roger A. H. Adan, Lars Alfredsson, Tetsuya Ando, Ole A. Andreassen & 192 others Jessica H. Baker, Wade H. Berrettini, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Matteo Cassina, Sven Cichon, Maurizio Clementi, Roger D. Cone, Philippe Courtet, Scott Crow, James J. Crowley, Unna N. Danner, Oliver S. P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Dimitris Dikeos, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo, Laramie E. Duncan, Karin Egberts, Stefan Ehrlich, Geòrgia Escaramís, Tõnu Esko, Xavier Estivill, Anne Farmer, Angela Favaro, Fernando Fernández-Aranda, Manfred M. Fichter, Krista Fischer, Manuel Föcker, Lenka Foretova, Andreas J. Forstner, Monica Forzan, Christopher S. Franklin, Steven Gallinger, Ina Giegling, Johanna Giuranna, Fragiskos Gonidakis, Philip Gorwood, Monica Gratacos Mayora, Sébastien Guillaume, Yiran Guo, Hakon Hakonarson, Konstantinos Hatzikotoulas, Joanna Hauser, Johannes Hebebrand, Sietske G. Helder, Stefan Herms, Beate Herpertz-Dahlmann, Wolfgang Herzog, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Susana Jiménez-Murcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J. H. Kas, James L. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Lars Klareskog, Kelly L. Klump, Gun Peggy S. Knudsen, Maria C. La Via, Stephanie Le Hellard, Robert D. Levitan, Dong Li, Lisa Lilenfeld, Bochao Danae Lin, Jolanta Lissowska, Jurjen Luykx, Pierre J. Magistretti, Mario Maj, Katrin Mannik, Sara Marsal, Christian R. Marshall, Morten Mattingsdal, Sara McDevitt, Peter McGuffin, Andres Metspalu, Ingrid Meulenbelt, Nadia Micali, Karen Mitchell, Alessio Maria Monteleone, Palmiero Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Roel A. Ophoff, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Dalila Pinto, Raquel Rabionet, Anu Raevuori, Nicolas Ramoz, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Alessandro Rotondo, Dan Rujescu, Filip Rybakowski, Paolo Santonastaso, André Scherag, Stephen W. Scherer, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C. T. Slof-Op ‘t Landt, Agnieszka Slopien, Sandro Sorbi, Beata Świątkowska, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Gudrun Wagner, Esther Walton, Elisabeth Widen, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Andrew W. Bergen, Joseph M. Boden, Harry Brandt, Steven Crawford, Katherine A. Halmi, L. John Horwood, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, James E. Mitchell, Catherine M. Olsen, John F. Pearson, Nancy L. Pedersen, Michael Strober, Thomas Werge, David C. Whiteman, D. Blake Woodside, Garret D. Stuber, Scott Gordon, Jakob Grove, Anjali K. Henders, Anders Juréus, Katherine M. Kirk, Janne T. Larsen, Richard Parker, Liselotte Petersen, Jennifer Jordan, Martin Kennedy, Grant W. Montgomery, Tracey D. Wade, Andreas Birgegård, Paul Lichtenstein, Claes Norring, Mikael Landén, Nicholas G. Martin, Preben Bo Mortensen, Patrick F. Sullivan, Gerome Breen, Cynthia M. Bulik, Anorexia Nervosa Genetics Initiative, Eating Disorders Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
Original languageEnglish
Pages (from-to)1207-1214
Number of pages8
JournalNature Genetics
Volume51
Early online date15 Jul 2019
DOIs
Publication statusPublished - Aug 2019

Fingerprint

Genome-Wide Association Study
Anorexia Nervosa
Psychiatry
Body Mass Index
Genomics
Exercise
Lipids
Mortality

Keywords

  • LD SCORE REGRESSION
  • EATING-DISORDERS
  • GENETIC CORRELATIONS
  • POLYGENIC RISK
  • COMORBIDITY
  • PREVALENCE
  • HERITABILITY
  • VARIANTS
  • INSIGHTS
  • MYC

ASJC Scopus subject areas

  • Genetics

Cite this

Watson, H. J., Yilmaz, Z., Thornton, L. M., Hübel, C., Coleman, J. R. I., Gaspar, H. A., ... Consortium, E. D. W. G. O. T. P. G. (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, 51, 1207-1214. https://doi.org/10.1038/s41588-019-0439-2

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. / Watson, Hunna J.; Yilmaz, Zeynep; Thornton, Laura M.; Hübel, Christopher; Coleman, Jonathan R. I.; Gaspar, Héléna A.; Bryois, Julien; Hinney, Anke; Leppä, Virpi M.; Mattheisen, Manuel; Medland, Sarah E.; Ripke, Stephan; Yao, Shuyang; Giusti-Rodríguez, Paola; Hanscombe, Ken B.; Purves, Kirstin L.; Adan, Roger A. H.; Alfredsson, Lars; Ando, Tetsuya; Andreassen, Ole A.; Baker, Jessica H.; Berrettini, Wade H.; Boehm, Ilka; Boni, Claudette; Perica, Vesna Boraska; Buehren, Katharina; Burghardt, Roland; Cassina, Matteo; Cichon, Sven; Clementi, Maurizio; Cone, Roger D.; Courtet, Philippe; Crow, Scott; Crowley, James J.; Danner, Unna N.; Davis, Oliver S. P.; de Zwaan, Martina; Dedoussis, George; Degortes, Daniela; DeSocio, Janiece E.; Dick, Danielle M.; Dikeos, Dimitris; Dina, Christian; Dmitrzak-Weglarz, Monika; Docampo, Elisa; Duncan, Laramie E.; Egberts, Karin; Ehrlich, Stefan; Escaramís, Geòrgia; Esko, Tõnu; Estivill, Xavier; Farmer, Anne; Favaro, Angela; Fernández-Aranda, Fernando; Fichter, Manfred M.; Fischer, Krista; Föcker, Manuel; Foretova, Lenka; Forstner, Andreas J.; Forzan, Monica; Franklin, Christopher S.; Gallinger, Steven; Giegling, Ina; Giuranna, Johanna; Gonidakis, Fragiskos; Gorwood, Philip; Mayora, Monica Gratacos; Guillaume, Sébastien; Guo, Yiran; Hakonarson, Hakon; Hatzikotoulas, Konstantinos; Hauser, Joanna; Hebebrand, Johannes; Helder, Sietske G.; Herms, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Huckins, Laura M.; Hudson, James I.; Imgart, Hartmut; Inoko, Hidetoshi; Janout, Vladimir; Jiménez-Murcia, Susana; Julià, Antonio; Kalsi, Gursharan; Kaminská, Deborah; Kaprio, Jaakko; Karhunen, Leila; Karwautz, Andreas; Kas, Martien J. H.; Kennedy, James L.; Keski-Rahkonen, Anna; Kiezebrink, Kirsty; Kim, Youl-Ri; Klareskog, Lars; Klump, Kelly L.; Knudsen, Gun Peggy S.; La Via, Maria C.; Le Hellard, Stephanie; Levitan, Robert D.; Li, Dong; Lilenfeld, Lisa; Lin, Bochao Danae; Lissowska, Jolanta; Luykx, Jurjen; Magistretti, Pierre J.; Maj, Mario; Mannik, Katrin; Marsal, Sara; Marshall, Christian R.; Mattingsdal, Morten; McDevitt, Sara; McGuffin, Peter; Metspalu, Andres; Meulenbelt, Ingrid; Micali, Nadia; Mitchell, Karen; Monteleone, Alessio Maria; Monteleone, Palmiero; Munn-Chernoff, Melissa A.; Nacmias, Benedetta; Navratilova, Marie; Ntalla, Ioanna; O’Toole, Julie K.; Ophoff, Roel A.; Padyukov, Leonid; Palotie, Aarno; Pantel, Jacques; Papezova, Hana; Pinto, Dalila; Rabionet, Raquel; Raevuori, Anu; Ramoz, Nicolas; Reichborn-Kjennerud, Ted; Ricca, Valdo; Ripatti, Samuli; Ritschel, Franziska; Roberts, Marion; Rotondo, Alessandro; Rujescu, Dan; Rybakowski, Filip; Santonastaso, Paolo; Scherag, André; Scherer, Stephen W.; Schmidt, Ulrike; Schork, Nicholas J.; Schosser, Alexandra; Seitz, Jochen; Slachtova, Lenka; Slagboom, P. Eline; Slof-Op ‘t Landt, Margarita C. T.; Slopien, Agnieszka; Sorbi, Sandro; Świątkowska, Beata; Szatkiewicz, Jin P.; Tachmazidou, Ioanna; Tenconi, Elena; Tortorella, Alfonso; Tozzi, Federica; Treasure, Janet; Tsitsika, Artemis; Tyszkiewicz-Nwafor, Marta; Tziouvas, Konstantinos; van Elburg, Annemarie A.; van Furth, Eric F.; Wagner, Gudrun; Walton, Esther; Widen, Elisabeth; Zeggini, Eleftheria; Zerwas, Stephanie; Zipfel, Stephan; Bergen, Andrew W.; Boden, Joseph M.; Brandt, Harry; Crawford, Steven; Halmi, Katherine A.; Horwood, L. John; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Mitchell, James E.; Olsen, Catherine M.; Pearson, John F.; Pedersen, Nancy L.; Strober, Michael; Werge, Thomas; Whiteman, David C.; Woodside, D. Blake; Stuber, Garret D.; Gordon, Scott; Grove, Jakob; Henders, Anjali K.; Juréus, Anders; Kirk, Katherine M.; Larsen, Janne T.; Parker, Richard; Petersen, Liselotte; Jordan, Jennifer; Kennedy, Martin; Montgomery, Grant W.; Wade, Tracey D.; Birgegård, Andreas; Lichtenstein, Paul; Norring, Claes; Landén, Mikael; Martin, Nicholas G.; Mortensen, Preben Bo; Sullivan, Patrick F.; Breen, Gerome; Bulik, Cynthia M. (Corresponding Author); Initiative, Anorexia Nervosa Genetics; Consortium, Eating Disorders Working Group of the Psychiatric Genomics.

In: Nature Genetics, Vol. 51, 08.2019, p. 1207-1214.

Research output: Contribution to journalArticle

Watson, HJ, Yilmaz, Z, Thornton, LM, Hübel, C, Coleman, JRI, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Medland, SE, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Purves, KL, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Baker, JH, Berrettini, WH, Boehm, I, Boni, C, Perica, VB, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OSP, de Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Mayora, MG, Guillaume, S, Guo, Y, Hakonarson, H, Hatzikotoulas, K, Hauser, J, Hebebrand, J, Helder, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Kaprio, J, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, Y-R, Klareskog, L, Klump, KL, Knudsen, GPS, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, Mattingsdal, M, McDevitt, S, McGuffin, P, Metspalu, A, Meulenbelt, I, Micali, N, Mitchell, K, Monteleone, AM, Monteleone, P, Munn-Chernoff, MA, Nacmias, B, Navratilova, M, Ntalla, I, O’Toole, JK, Ophoff, RA, Padyukov, L, Palotie, A, Pantel, J, Papezova, H, Pinto, D, Rabionet, R, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Santonastaso, P, Scherag, A, Scherer, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op ‘t Landt, MCT, Slopien, A, Sorbi, S, Świątkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, JE, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Stuber, GD, Gordon, S, Grove, J, Henders, AK, Juréus, A, Kirk, KM, Larsen, JT, Parker, R, Petersen, L, Jordan, J, Kennedy, M, Montgomery, GW, Wade, TD, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Martin, NG, Mortensen, PB, Sullivan, PF, Breen, G, Bulik, CM, Initiative, ANG & Consortium, EDWGOTPG 2019, 'Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa', Nature Genetics, vol. 51, pp. 1207-1214. https://doi.org/10.1038/s41588-019-0439-2
Watson, Hunna J. ; Yilmaz, Zeynep ; Thornton, Laura M. ; Hübel, Christopher ; Coleman, Jonathan R. I. ; Gaspar, Héléna A. ; Bryois, Julien ; Hinney, Anke ; Leppä, Virpi M. ; Mattheisen, Manuel ; Medland, Sarah E. ; Ripke, Stephan ; Yao, Shuyang ; Giusti-Rodríguez, Paola ; Hanscombe, Ken B. ; Purves, Kirstin L. ; Adan, Roger A. H. ; Alfredsson, Lars ; Ando, Tetsuya ; Andreassen, Ole A. ; Baker, Jessica H. ; Berrettini, Wade H. ; Boehm, Ilka ; Boni, Claudette ; Perica, Vesna Boraska ; Buehren, Katharina ; Burghardt, Roland ; Cassina, Matteo ; Cichon, Sven ; Clementi, Maurizio ; Cone, Roger D. ; Courtet, Philippe ; Crow, Scott ; Crowley, James J. ; Danner, Unna N. ; Davis, Oliver S. P. ; de Zwaan, Martina ; Dedoussis, George ; Degortes, Daniela ; DeSocio, Janiece E. ; Dick, Danielle M. ; Dikeos, Dimitris ; Dina, Christian ; Dmitrzak-Weglarz, Monika ; Docampo, Elisa ; Duncan, Laramie E. ; Egberts, Karin ; Ehrlich, Stefan ; Escaramís, Geòrgia ; Esko, Tõnu ; Estivill, Xavier ; Farmer, Anne ; Favaro, Angela ; Fernández-Aranda, Fernando ; Fichter, Manfred M. ; Fischer, Krista ; Föcker, Manuel ; Foretova, Lenka ; Forstner, Andreas J. ; Forzan, Monica ; Franklin, Christopher S. ; Gallinger, Steven ; Giegling, Ina ; Giuranna, Johanna ; Gonidakis, Fragiskos ; Gorwood, Philip ; Mayora, Monica Gratacos ; Guillaume, Sébastien ; Guo, Yiran ; Hakonarson, Hakon ; Hatzikotoulas, Konstantinos ; Hauser, Joanna ; Hebebrand, Johannes ; Helder, Sietske G. ; Herms, Stefan ; Herpertz-Dahlmann, Beate ; Herzog, Wolfgang ; Huckins, Laura M. ; Hudson, James I. ; Imgart, Hartmut ; Inoko, Hidetoshi ; Janout, Vladimir ; Jiménez-Murcia, Susana ; Julià, Antonio ; Kalsi, Gursharan ; Kaminská, Deborah ; Kaprio, Jaakko ; Karhunen, Leila ; Karwautz, Andreas ; Kas, Martien J. H. ; Kennedy, James L. ; Keski-Rahkonen, Anna ; Kiezebrink, Kirsty ; Kim, Youl-Ri ; Klareskog, Lars ; Klump, Kelly L. ; Knudsen, Gun Peggy S. ; La Via, Maria C. ; Le Hellard, Stephanie ; Levitan, Robert D. ; Li, Dong ; Lilenfeld, Lisa ; Lin, Bochao Danae ; Lissowska, Jolanta ; Luykx, Jurjen ; Magistretti, Pierre J. ; Maj, Mario ; Mannik, Katrin ; Marsal, Sara ; Marshall, Christian R. ; Mattingsdal, Morten ; McDevitt, Sara ; McGuffin, Peter ; Metspalu, Andres ; Meulenbelt, Ingrid ; Micali, Nadia ; Mitchell, Karen ; Monteleone, Alessio Maria ; Monteleone, Palmiero ; Munn-Chernoff, Melissa A. ; Nacmias, Benedetta ; Navratilova, Marie ; Ntalla, Ioanna ; O’Toole, Julie K. ; Ophoff, Roel A. ; Padyukov, Leonid ; Palotie, Aarno ; Pantel, Jacques ; Papezova, Hana ; Pinto, Dalila ; Rabionet, Raquel ; Raevuori, Anu ; Ramoz, Nicolas ; Reichborn-Kjennerud, Ted ; Ricca, Valdo ; Ripatti, Samuli ; Ritschel, Franziska ; Roberts, Marion ; Rotondo, Alessandro ; Rujescu, Dan ; Rybakowski, Filip ; Santonastaso, Paolo ; Scherag, André ; Scherer, Stephen W. ; Schmidt, Ulrike ; Schork, Nicholas J. ; Schosser, Alexandra ; Seitz, Jochen ; Slachtova, Lenka ; Slagboom, P. Eline ; Slof-Op ‘t Landt, Margarita C. T. ; Slopien, Agnieszka ; Sorbi, Sandro ; Świątkowska, Beata ; Szatkiewicz, Jin P. ; Tachmazidou, Ioanna ; Tenconi, Elena ; Tortorella, Alfonso ; Tozzi, Federica ; Treasure, Janet ; Tsitsika, Artemis ; Tyszkiewicz-Nwafor, Marta ; Tziouvas, Konstantinos ; van Elburg, Annemarie A. ; van Furth, Eric F. ; Wagner, Gudrun ; Walton, Esther ; Widen, Elisabeth ; Zeggini, Eleftheria ; Zerwas, Stephanie ; Zipfel, Stephan ; Bergen, Andrew W. ; Boden, Joseph M. ; Brandt, Harry ; Crawford, Steven ; Halmi, Katherine A. ; Horwood, L. John ; Johnson, Craig ; Kaplan, Allan S. ; Kaye, Walter H. ; Mitchell, James E. ; Olsen, Catherine M. ; Pearson, John F. ; Pedersen, Nancy L. ; Strober, Michael ; Werge, Thomas ; Whiteman, David C. ; Woodside, D. Blake ; Stuber, Garret D. ; Gordon, Scott ; Grove, Jakob ; Henders, Anjali K. ; Juréus, Anders ; Kirk, Katherine M. ; Larsen, Janne T. ; Parker, Richard ; Petersen, Liselotte ; Jordan, Jennifer ; Kennedy, Martin ; Montgomery, Grant W. ; Wade, Tracey D. ; Birgegård, Andreas ; Lichtenstein, Paul ; Norring, Claes ; Landén, Mikael ; Martin, Nicholas G. ; Mortensen, Preben Bo ; Sullivan, Patrick F. ; Breen, Gerome ; Bulik, Cynthia M. ; Initiative, Anorexia Nervosa Genetics ; Consortium, Eating Disorders Working Group of the Psychiatric Genomics. / Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. In: Nature Genetics. 2019 ; Vol. 51. pp. 1207-1214.
@article{54ea1e6445a74e1d933fc2ae8d0cc04c,
title = "Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa",
abstract = "Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4{\%} of women and 0.3{\%} of men2–4, with twin-based heritability estimates of 50–60{\%}5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.",
keywords = "LD SCORE REGRESSION, EATING-DISORDERS, GENETIC CORRELATIONS, POLYGENIC RISK, COMORBIDITY, PREVALENCE, HERITABILITY, VARIANTS, INSIGHTS, MYC",
author = "Watson, {Hunna J.} and Zeynep Yilmaz and Thornton, {Laura M.} and Christopher H{\"u}bel and Coleman, {Jonathan R. I.} and Gaspar, {H{\'e}l{\'e}na A.} and Julien Bryois and Anke Hinney and Lepp{\"a}, {Virpi M.} and Manuel Mattheisen and Medland, {Sarah E.} and Stephan Ripke and Shuyang Yao and Paola Giusti-Rodr{\'i}guez and Hanscombe, {Ken B.} and Purves, {Kirstin L.} and Adan, {Roger A. H.} and Lars Alfredsson and Tetsuya Ando and Andreassen, {Ole A.} and Baker, {Jessica H.} and Berrettini, {Wade H.} and Ilka Boehm and Claudette Boni and Perica, {Vesna Boraska} and Katharina Buehren and Roland Burghardt and Matteo Cassina and Sven Cichon and Maurizio Clementi and Cone, {Roger D.} and Philippe Courtet and Scott Crow and Crowley, {James J.} and Danner, {Unna N.} and Davis, {Oliver S. P.} and {de Zwaan}, Martina and George Dedoussis and Daniela Degortes and DeSocio, {Janiece E.} and Dick, {Danielle M.} and Dimitris Dikeos and Christian Dina and Monika Dmitrzak-Weglarz and Elisa Docampo and Duncan, {Laramie E.} and Karin Egberts and Stefan Ehrlich and Ge{\`o}rgia Escaram{\'i}s and T{\~o}nu Esko and Xavier Estivill and Anne Farmer and Angela Favaro and Fernando Fern{\'a}ndez-Aranda and Fichter, {Manfred M.} and Krista Fischer and Manuel F{\"o}cker and Lenka Foretova and Forstner, {Andreas J.} and Monica Forzan and Franklin, {Christopher S.} and Steven Gallinger and Ina Giegling and Johanna Giuranna and Fragiskos Gonidakis and Philip Gorwood and Mayora, {Monica Gratacos} and S{\'e}bastien Guillaume and Yiran Guo and Hakon Hakonarson and Konstantinos Hatzikotoulas and Joanna Hauser and Johannes Hebebrand and Helder, {Sietske G.} and Stefan Herms and Beate Herpertz-Dahlmann and Wolfgang Herzog and Huckins, {Laura M.} and Hudson, {James I.} and Hartmut Imgart and Hidetoshi Inoko and Vladimir Janout and Susana Jim{\'e}nez-Murcia and Antonio Juli{\`a} and Gursharan Kalsi and Deborah Kaminsk{\'a} and Jaakko Kaprio and Leila Karhunen and Andreas Karwautz and Kas, {Martien J. H.} and Kennedy, {James L.} and Anna Keski-Rahkonen and Kirsty Kiezebrink and Youl-Ri Kim and Lars Klareskog and Klump, {Kelly L.} and Knudsen, {Gun Peggy S.} and {La Via}, {Maria C.} and {Le Hellard}, Stephanie and Levitan, {Robert D.} and Dong Li and Lisa Lilenfeld and Lin, {Bochao Danae} and Jolanta Lissowska and Jurjen Luykx and Magistretti, {Pierre J.} and Mario Maj and Katrin Mannik and Sara Marsal and Marshall, {Christian R.} and Morten Mattingsdal and Sara McDevitt and Peter McGuffin and Andres Metspalu and Ingrid Meulenbelt and Nadia Micali and Karen Mitchell and Monteleone, {Alessio Maria} and Palmiero Monteleone and Munn-Chernoff, {Melissa A.} and Benedetta Nacmias and Marie Navratilova and Ioanna Ntalla and O’Toole, {Julie K.} and Ophoff, {Roel A.} and Leonid Padyukov and Aarno Palotie and Jacques Pantel and Hana Papezova and Dalila Pinto and Raquel Rabionet and Anu Raevuori and Nicolas Ramoz 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 Scherer, {Stephen W.} and Ulrike Schmidt and Schork, {Nicholas J.} and Alexandra Schosser and Jochen Seitz and Lenka Slachtova and Slagboom, {P. Eline} and {Slof-Op ‘t Landt}, {Margarita C. T.} and Agnieszka Slopien and Sandro Sorbi and Beata Świątkowska and Szatkiewicz, {Jin P.} and Ioanna Tachmazidou and Elena Tenconi and Alfonso Tortorella and Federica Tozzi and Janet Treasure and Artemis Tsitsika and Marta Tyszkiewicz-Nwafor and Konstantinos Tziouvas and {van Elburg}, {Annemarie A.} and {van Furth}, {Eric F.} and Gudrun Wagner and Esther Walton and Elisabeth Widen and Eleftheria Zeggini and Stephanie Zerwas and Stephan Zipfel and Bergen, {Andrew W.} and Boden, {Joseph M.} and Harry Brandt and Steven Crawford and Halmi, {Katherine A.} and Horwood, {L. John} and Craig Johnson and Kaplan, {Allan S.} and Kaye, {Walter H.} and Mitchell, {James E.} and Olsen, {Catherine M.} and Pearson, {John F.} and Pedersen, {Nancy L.} and Michael Strober and Thomas Werge and Whiteman, {David C.} and Woodside, {D. Blake} and Stuber, {Garret D.} and Scott Gordon and Jakob Grove and Henders, {Anjali K.} and Anders Jur{\'e}us and Kirk, {Katherine M.} and Larsen, {Janne T.} and Richard Parker and Liselotte Petersen and Jennifer Jordan and Martin Kennedy and Montgomery, {Grant W.} and Wade, {Tracey D.} and Andreas Birgeg{\aa}rd and Paul Lichtenstein and Claes Norring and Mikael Land{\'e}n and Martin, {Nicholas G.} and Mortensen, {Preben Bo} and Sullivan, {Patrick F.} and Gerome Breen and Bulik, {Cynthia M.} and Initiative, {Anorexia Nervosa Genetics} and Consortium, {Eating Disorders Working Group of the Psychiatric Genomics}",
note = "Grant support for ANGI, the PGC-ED and its component groups is shown in Supplementary Table 17. We thank all study volunteers, study coordinators and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative is an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We are deeply grateful to all of the individuals who, through their participation, made ANGI a success. The goodwill that permeated the eating disorders community fueled by the enthusiasm of prominent bloggers, advocates, clinicians, treatment centers, scientists, organizations, families and especially those who have suffered from anorexia nervosa, yielded in an unprecedented and inspired global movement to complete this science. ANGI (United States): We thank Walden Behavioral Care, McCallum Place and the Renfrew Center for assisting with recruitment. We express our gratitude to J. Alexander (http://www.junealexander.com/) and C. Arnold (http://carriearnold.com/), who helped us disseminate information about ANGI. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS), the Carolina Data Warehouse and the Foundation of Hope, Raleigh, North Carolina. ANGI (Australia and New Zealand): We thank the Australia & and New Zealand Academy for Eating Disorders for assistance with recruitment and publicity. We thank VIVA! Communications for their efforts in promoting the study and the Butterfly Foundation for their ongoing support of anorexia nervosa research in Australia and EDANZ in New Zealand. We thank the QSkin Sun and Health Study for controls. We also acknowledge the assistance of S. Maguire and J. Russell (University of Sydney), P. Hay (Western Sydney University), S. Madden (Western Sydney University and the Sydney Children’s Hospital Network), S. Sawyer and E. Hughes (Royal Children’s Hospital, Melbourne), K. Fairweather-Schmidt (Flinders University), A. Fursland (Centre for Clinical Interventions and Curtin University), J. McCormack (Princess Margaret Hospital for Children), F. Wagg (Royal Hobart Hospital) and W. Ward (Royal Brisbane and Women’s Hospital) in recruitment. We also thank L. Nunn for validation work on the ED100Kv1 Questionnaire. Additionally, administrative support for data collection was received from the Australian Twin Registry, which is supported by an Enabling Grant (ID 310667) from the NHMRC administered by the University of Melbourne. In New Zealand, we also acknowledge assistance with recruitment from M. Roberts (University of Auckland), R. Lawson (South Island Eating Disorders Service), M. Meiklejohn (Auckland District Health Board) and R. Mysliwiec. Special thanks to those who provided their stories in relation to publicity about ANGI. ANGI (Sweden): We acknowledge the assistance of the Stockholm Centre for Eating Disorders (SC{\"A}) and thank the Swedish National Quality Register for Eating Disorders (Riks{\"a}t) and Lifegene. We would also like to thank the research nurses and data collectors at the Department of Medical Epidemiology and Biostatistics who worked on ANGI. ANGI (Denmark): We thank the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children’s Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the UK Biobank and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank M. Lam for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR BioResource. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was also supported by the National Institute of Mental Health of the US National Institutes of Health under Award Numbers U01MH109528 and U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.",
year = "2019",
month = "8",
doi = "10.1038/s41588-019-0439-2",
language = "English",
volume = "51",
pages = "1207--1214",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

AU - Watson, Hunna J.

AU - Yilmaz, Zeynep

AU - Thornton, Laura M.

AU - Hübel, Christopher

AU - Coleman, Jonathan R. I.

AU - Gaspar, Héléna A.

AU - Bryois, Julien

AU - Hinney, Anke

AU - Leppä, Virpi M.

AU - Mattheisen, Manuel

AU - Medland, Sarah E.

AU - Ripke, Stephan

AU - Yao, Shuyang

AU - Giusti-Rodríguez, Paola

AU - Hanscombe, Ken B.

AU - Purves, Kirstin L.

AU - Adan, Roger A. H.

AU - Alfredsson, Lars

AU - Ando, Tetsuya

AU - Andreassen, Ole A.

AU - Baker, Jessica H.

AU - Berrettini, Wade H.

AU - Boehm, Ilka

AU - Boni, Claudette

AU - Perica, Vesna Boraska

AU - Buehren, Katharina

AU - Burghardt, Roland

AU - Cassina, Matteo

AU - Cichon, Sven

AU - Clementi, Maurizio

AU - Cone, Roger D.

AU - Courtet, Philippe

AU - Crow, Scott

AU - Crowley, James J.

AU - Danner, Unna N.

AU - Davis, Oliver S. P.

AU - de Zwaan, Martina

AU - Dedoussis, George

AU - Degortes, Daniela

AU - DeSocio, Janiece E.

AU - Dick, Danielle M.

AU - Dikeos, Dimitris

AU - Dina, Christian

AU - Dmitrzak-Weglarz, Monika

AU - Docampo, Elisa

AU - Duncan, Laramie E.

AU - Egberts, Karin

AU - Ehrlich, Stefan

AU - Escaramís, Geòrgia

AU - Esko, Tõnu

AU - Estivill, Xavier

AU - Farmer, Anne

AU - Favaro, Angela

AU - Fernández-Aranda, Fernando

AU - Fichter, Manfred M.

AU - Fischer, Krista

AU - Föcker, Manuel

AU - Foretova, Lenka

AU - Forstner, Andreas J.

AU - Forzan, Monica

AU - Franklin, Christopher S.

AU - Gallinger, Steven

AU - Giegling, Ina

AU - Giuranna, Johanna

AU - Gonidakis, Fragiskos

AU - Gorwood, Philip

AU - Mayora, Monica Gratacos

AU - Guillaume, Sébastien

AU - Guo, Yiran

AU - Hakonarson, Hakon

AU - Hatzikotoulas, Konstantinos

AU - Hauser, Joanna

AU - Hebebrand, Johannes

AU - Helder, Sietske G.

AU - Herms, Stefan

AU - Herpertz-Dahlmann, Beate

AU - Herzog, Wolfgang

AU - Huckins, Laura M.

AU - Hudson, James I.

AU - Imgart, Hartmut

AU - Inoko, Hidetoshi

AU - Janout, Vladimir

AU - Jiménez-Murcia, Susana

AU - Julià, Antonio

AU - Kalsi, Gursharan

AU - Kaminská, Deborah

AU - Kaprio, Jaakko

AU - Karhunen, Leila

AU - Karwautz, Andreas

AU - Kas, Martien J. H.

AU - Kennedy, James L.

AU - Keski-Rahkonen, Anna

AU - Kiezebrink, Kirsty

AU - Kim, Youl-Ri

AU - Klareskog, Lars

AU - Klump, Kelly L.

AU - Knudsen, Gun Peggy S.

AU - La Via, Maria C.

AU - Le Hellard, Stephanie

AU - Levitan, Robert D.

AU - Li, Dong

AU - Lilenfeld, Lisa

AU - Lin, Bochao Danae

AU - Lissowska, Jolanta

AU - Luykx, Jurjen

AU - Magistretti, Pierre J.

AU - Maj, Mario

AU - Mannik, Katrin

AU - Marsal, Sara

AU - Marshall, Christian R.

AU - Mattingsdal, Morten

AU - McDevitt, Sara

AU - McGuffin, Peter

AU - Metspalu, Andres

AU - Meulenbelt, Ingrid

AU - Micali, Nadia

AU - Mitchell, Karen

AU - Monteleone, Alessio Maria

AU - Monteleone, Palmiero

AU - Munn-Chernoff, Melissa A.

AU - Nacmias, Benedetta

AU - Navratilova, Marie

AU - Ntalla, Ioanna

AU - O’Toole, Julie K.

AU - Ophoff, Roel A.

AU - Padyukov, Leonid

AU - Palotie, Aarno

AU - Pantel, Jacques

AU - Papezova, Hana

AU - Pinto, Dalila

AU - Rabionet, Raquel

AU - Raevuori, Anu

AU - Ramoz, Nicolas

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 W.

AU - Schmidt, Ulrike

AU - Schork, Nicholas J.

AU - Schosser, Alexandra

AU - Seitz, Jochen

AU - Slachtova, Lenka

AU - Slagboom, P. Eline

AU - Slof-Op ‘t Landt, Margarita C. T.

AU - Slopien, Agnieszka

AU - Sorbi, Sandro

AU - Świątkowska, Beata

AU - Szatkiewicz, Jin P.

AU - Tachmazidou, Ioanna

AU - Tenconi, Elena

AU - Tortorella, Alfonso

AU - Tozzi, Federica

AU - Treasure, Janet

AU - Tsitsika, Artemis

AU - Tyszkiewicz-Nwafor, Marta

AU - Tziouvas, Konstantinos

AU - van Elburg, Annemarie A.

AU - van Furth, Eric F.

AU - Wagner, Gudrun

AU - Walton, Esther

AU - Widen, Elisabeth

AU - Zeggini, Eleftheria

AU - Zerwas, Stephanie

AU - Zipfel, Stephan

AU - Bergen, Andrew W.

AU - Boden, Joseph M.

AU - Brandt, Harry

AU - Crawford, Steven

AU - Halmi, Katherine A.

AU - Horwood, L. John

AU - Johnson, Craig

AU - Kaplan, Allan S.

AU - Kaye, Walter H.

AU - Mitchell, James E.

AU - Olsen, Catherine M.

AU - Pearson, John F.

AU - Pedersen, Nancy L.

AU - Strober, Michael

AU - Werge, Thomas

AU - Whiteman, David C.

AU - Woodside, D. Blake

AU - Stuber, Garret D.

AU - Gordon, Scott

AU - Grove, Jakob

AU - Henders, Anjali K.

AU - Juréus, Anders

AU - Kirk, Katherine M.

AU - Larsen, Janne T.

AU - Parker, Richard

AU - Petersen, Liselotte

AU - Jordan, Jennifer

AU - Kennedy, Martin

AU - Montgomery, Grant W.

AU - Wade, Tracey D.

AU - Birgegård, Andreas

AU - Lichtenstein, Paul

AU - Norring, Claes

AU - Landén, Mikael

AU - Martin, Nicholas G.

AU - Mortensen, Preben Bo

AU - Sullivan, Patrick F.

AU - Breen, Gerome

AU - Bulik, Cynthia M.

AU - Initiative, Anorexia Nervosa Genetics

AU - Consortium, Eating Disorders Working Group of the Psychiatric Genomics

N1 - Grant support for ANGI, the PGC-ED and its component groups is shown in Supplementary Table 17. We thank all study volunteers, study coordinators and research staff who enabled this study. ANGI: The Anorexia Nervosa Genetics Initiative is an initiative of the Klarman Family Foundation. Additional support was offered by the National Institute of Mental Health. We are deeply grateful to all of the individuals who, through their participation, made ANGI a success. The goodwill that permeated the eating disorders community fueled by the enthusiasm of prominent bloggers, advocates, clinicians, treatment centers, scientists, organizations, families and especially those who have suffered from anorexia nervosa, yielded in an unprecedented and inspired global movement to complete this science. ANGI (United States): We thank Walden Behavioral Care, McCallum Place and the Renfrew Center for assisting with recruitment. We express our gratitude to J. Alexander (http://www.junealexander.com/) and C. Arnold (http://carriearnold.com/), who helped us disseminate information about ANGI. We acknowledge support from the North Carolina Translational and Clinical Sciences Institute (NC TraCS), the Carolina Data Warehouse and the Foundation of Hope, Raleigh, North Carolina. ANGI (Australia and New Zealand): We thank the Australia & and New Zealand Academy for Eating Disorders for assistance with recruitment and publicity. We thank VIVA! Communications for their efforts in promoting the study and the Butterfly Foundation for their ongoing support of anorexia nervosa research in Australia and EDANZ in New Zealand. We thank the QSkin Sun and Health Study for controls. We also acknowledge the assistance of S. Maguire and J. Russell (University of Sydney), P. Hay (Western Sydney University), S. Madden (Western Sydney University and the Sydney Children’s Hospital Network), S. Sawyer and E. Hughes (Royal Children’s Hospital, Melbourne), K. Fairweather-Schmidt (Flinders University), A. Fursland (Centre for Clinical Interventions and Curtin University), J. McCormack (Princess Margaret Hospital for Children), F. Wagg (Royal Hobart Hospital) and W. Ward (Royal Brisbane and Women’s Hospital) in recruitment. We also thank L. Nunn for validation work on the ED100Kv1 Questionnaire. Additionally, administrative support for data collection was received from the Australian Twin Registry, which is supported by an Enabling Grant (ID 310667) from the NHMRC administered by the University of Melbourne. In New Zealand, we also acknowledge assistance with recruitment from M. Roberts (University of Auckland), R. Lawson (South Island Eating Disorders Service), M. Meiklejohn (Auckland District Health Board) and R. Mysliwiec. Special thanks to those who provided their stories in relation to publicity about ANGI. ANGI (Sweden): We acknowledge the assistance of the Stockholm Centre for Eating Disorders (SCÄ) and thank the Swedish National Quality Register for Eating Disorders (Riksät) and Lifegene. We would also like to thank the research nurses and data collectors at the Department of Medical Epidemiology and Biostatistics who worked on ANGI. ANGI (Denmark): We thank the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). PGC: We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of individuals who have shared their life experiences with PGC investigators and the contributing studies. We are grateful to the Children’s Hospital of Philadelphia (CHOP), the Price Foundation Collaborative Group (PFCG), Genetic Consortium for Anorexia Nervosa (GCAN), Wellcome Trust Case-Control Consortium-3 (WTCCC-3), the UK Biobank and all PGC-ED members for their support in providing individual samples used in this study. We thank SURFsara (http://www.surf.nl) for support in using the Lisa Compute Cluster. We thank M. Lam for Ricopili consultation. This study also represents independent research partly funded by the English National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR BioResource. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the English Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). Research reported in this publication was also supported by the National Institute of Mental Health of the US National Institutes of Health under Award Numbers U01MH109528 and U01MH109514. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.

PY - 2019/8

Y1 - 2019/8

N2 - Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

AB - Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

KW - LD SCORE REGRESSION

KW - EATING-DISORDERS

KW - GENETIC CORRELATIONS

KW - POLYGENIC RISK

KW - COMORBIDITY

KW - PREVALENCE

KW - HERITABILITY

KW - VARIANTS

KW - INSIGHTS

KW - MYC

UR - http://www.nature.com/articles/s41588-019-0439-2

UR - http://www.mendeley.com/research/genomewide-association-study-identifies-eight-risk-loci-implicates-metabopsychiatric-origins-anorexi

UR - http://www.scopus.com/inward/record.url?scp=85068455956&partnerID=8YFLogxK

U2 - 10.1038/s41588-019-0439-2

DO - 10.1038/s41588-019-0439-2

M3 - Article

VL - 51

SP - 1207

EP - 1214

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -