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A genome-wide association study of anorexia nervosa

Molecular Psychiatry volume 19, pages 1085–1094 (2014)Cite this article

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Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

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Acknowledgements

ACKNOWLEDGMENT FOR FUNDING, BIOMATERIALS, AND CLINICAL DATA

This work was funded by a grant from the WTCCC3 WT088827/Z/09 entitled ‘A genomewide association study of anorexia nervosa’.

WELLCOME TRUST ACKNOWLEDGMENTS

1 This work was supported by the WellcomeTrust (098051).

2 Eleftheria Zeggini is supported by the Wellcome Trust (098051).

3 Vesna Boraska is supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM (‘Gaining Experience’ Grant 2A), The National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN- Postdoc fellowship) and the Wellcome Trust (098051).

4 Christopher S Franklin is supported by the WTCCC3 project, which is supported by the Wellcome Trust (WT090355/A/09/Z, WT090355/B/09/Z).

5 James A B Floyd is supported by the WTCCC3 project, which is supported by the Wellcome Trust (WT090355/A/09/Z, WT090355/B/09/Z).

6 Lorraine Southam is supported by the Wellcome Trust (098051).

7 William N Rayner is supported by the Wellcome Trust (098051).

8 The Wellcome Trust Case Control Consortium 3 project is supported by the Wellcome Trust (WT090355/A/09/Z, WT090355/B/09/Z).

9 We acknowledge use of data from the British 1958 Birth Cohort and the UK National Blood Service.

10 We obtained High Density SNP Association Analysis of Melanoma: Case-Control and Outcomes Investigation data set through dbGaP (dbGaP Study Accession: phs000187.v1.p1). Research support to collect data and develop an application to support this project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740 and 5R01CA133996.

11 Laura Huckins acknowledges Wellcome Trust (098051) and the MRC (MR/J500355/1) and Ximena Ibarra-Soria for advice on RNA-seq analysis.

ACKNOWLEDGMENTS FOR CASES

Austria, Medical University of Vienna: The study was partly supported by the European Commission, Framework 5 research program, Integrated Project QLK1-CT-1999-00916 ‘Factors in Healthy Eating’ given to the consortium lead by Professor J Treasure and Professor D Collier, London. We thank Gerald Nobis, Dr Maria Haidvogl and Dr Julia Philipp for help with data collection and interview work.

Canada, Canadian Institutes of Health Research (CIHR): Zeynep Yilmaz was supported by a CIHR Doctoral Research Award (Genetic Determinants of Low Body Weight in Anorexia Nervosa; funding reference: GSD-111968). The Toronto authors thank Sajid Shaikh, Maria Tampakeras and Natalie Freeman for DNA preparation and laboratory support.

Canada, The Ontario Mental Health Foundation (OMHF): The collection of the Toronto DNA samples was supported by a grant from the OMHF, awarded to Allan S Kaplan and Robert D Levitan (Polymorphism in Serotonin System Genes: Putative Role in Increased Eating Behaviour in Seasonal Affective Disorder and Bulimia Nervosa).

Czech Republic, Charles University: The study was supported by Grants IGA MZ ČR NS/10045-4 and IGA NT 14094/3 from the Czech Ministry of Education and Health and PRVOUK P24/LF1/3 and P26/LF1/4 Charles University, Prague, and from the Marie Curie Research Training Network INTACT (MRTN-CT-2006-035988).

Finland, University of Helsinki: Academy of Finland Center of Excellence in Complex Disease Genetics (Grant numbers: 213506, 129680), ENGAGE—European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, Grant agreement number 201413. Data collection in the Finnish Twin studies has been supported by the National Institute of Alcohol Abuse and Alcoholism (Grants AA-12502, AA-00145 and AA-09203 to RJ Rose and AA15416 and K02AA018755 to DM Dick), the Academy of Finland (Grants 100499, 205585, 118555 and 141054, 265240 and 264146 to JK). AR and LK were supported by the Academy of Finland, Grants 259764 and 28327, respectively.

France, Institut National de la Santé et de la Recherche Médicale (INSERM), France: This French cohort was recruited with grants from EC Framework V ‘Factors in Healthy Eating’ (a consortium coordinated by Janet Treasure and David Collier, King’s College London), and from INRA/INSERM (4M406D), and the participation of Audrey Versini’s work was supported by grants from ‘Région Ile-de-France’. Cases were ascertained from Sainte-Anne Hospital (Paris) and Robert Debre Hospital (Paris).

Genetics of Anorexia Nervosa (GAN), National Institute of Mental Health: The data and collection of biomaterials for the GAN study have been supported by the National Institutes of Health Grants (MH066122, MH066117, MH066145, MH066296, MH066147, MH0662, MH066193, MH066287, MH066288 and MH066146). The principal investigators and co-investigators of this study were University of Pittsburgh, Pittsburgh, PA: Walter Kaye, M.D., Bernie Devlin, Ph.D.; University of North Carolina at Chapel Hill, Chapel Hill, NC: Cynthia M Bulik, Ph.D.; Roseneck Hospital for Behavioral Medicine, Prien and Department of Psychiatry, University of Munich, Germany: Manfred M Fichter, M.D.; Kings College London, Institute of Psychiatry, London, UK: Janet Treasure, M.D.; Toronto General Hospital, Toronto, Ontario, Canada: Allan Kaplan, M.D., D. Blake Woodside, M.D.; Laureate Psychiatric Hospital, Tulsa, OK: Craig L. Johnson, Ph. D.; Weill Cornell Medical College, White Plains, NY: Katherine Halmi, M.D.; Sheppard Pratt Health System, Towson: Harry A. Brandt, M.D., Steve Crawford, M.D.; Neuropsychiatric Research Institute, Fargo, ND; James E. Mitchell, M.D.; University of California at Los Angeles, Los Angeles, CA: Michael Strober, Ph.D.; University of Pennsylvania, Philadelphia, PA: Wade Berrettini, M.D., Ph.D.; and University of Birmingham, England: Ian Jones, M.D. We are indebted to the participating families for their contribution of time and effort in support of this study. We thank the Price Foundation for sponsoring the earlier work of this collaboration and also thank the study managers and clinical interviewers for their efforts in participant screening and clinical assessments.

Germany, University of Duisburg-Essen: Sample collection was funded by grants from the German Federal Ministry of Education and Research (BMBF; EDNET 01GV0602, 01GV0624, 01GV0623 and 01GV0905, NGFNplus: 01GS0820) and the IFORES program of the University of Duisburg-Essen. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Germany, Professor Ehrlich’s work is supported by DFG Grant EH 367/5-1 and the SFB 940.

GlaxoSmithKline (GSK), Leeds (Yorkshire Centre for Eating Disorders): We acknowledge the support of the Medical Research Council and GlaxoSmithKline for providing financial support of this project. The support of the Carnegie Trust in the form of a travel award is also acknowledged. We also acknowledge the help and support of the Discovery and Pipeline Genetics, and Translational Medicine and Genetics departments at GSK for their contributions to this study. In particular, they also acknowledge Mike Stubbins, Julia Perry, Sarah Bujac, David Campbell (at GSK currently or at the time when the study was performed), John Blundell (Leeds University) and Evleen Mann (Yorkshire Centre for Eating Disorders), for their fundamental contribution to the realization of this study.

Greece, Eating Disorders Unit, 1st Department of Psychiatry, Athens University, Medical School. Special thanks goes to Associate Professor Varsou E, Head of Eating Disorders Unit, and Professor Papadimitriou G, Chairman and Director of 1st Department of Psychiatry, Athens University, Medical School, for their advice and support.

Italy, Padua (BIOVEDA): BIOVEDA was funded thanks to a Grant of Veneto Region in 2009. Samples were collected at Padua, Verona, Treviso, Vicenza and Portogruaro hospitals.

Netherlands, Department of Translational Neuroscience, The Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht and Rintveld, Center for Eating Disorders, Altrecht in Zeist: Marek K. Brandys was supported by funding from the Marie Curie Research Training Network INTACT (Individually tailored stepped care for women with eating disorders; reference number: MRTN-CT-2006-035988). Martien Kas was supported by a ZonMW VIDI-Grant (91786327) from The Netherlands Organization for Scientific Research (NWO).

Norway, The National Institute of Public Health Twin Panel (NIPHTP): The NIPHTP was supported in part by grants from The Norwegian Research Council, The Norwegian Foundation for Health and Rehabilitation, The Norwegian Council for Mental Health and The European Commission under the program ‘Quality of Life and Management of the Living Resources’ of 5th Framework Program (no. QLG2-CT-2002-01254).

Poland, Poznan University of Medical Sciences (PUMS): PUMS study was sponsored by KBN scientific Grant no. PO5B 12823

Spain, Center for Genomic Regulation (CRG), Barcelona. Spanish Plan Nacional SAF2008-00357 (NOVADIS); the Generalitat de Catalunya AGAUR 2009 SGR-1502; the Instituto de Salud Carlos III (FIS/FEDER PI11/00733); and the European Commission 7th Framework Program, Project N. 261123 (GEUVADIS), and Project N. 262055 (ESGI).

Spain, Department of Psychiatry University Hospital of Bellvitge-IDIBELL, Barcelona: Financial support was received from Fondo de Investigación Sanitaria—FIS (PI11/210) and AGAUR (2009SGR1554). CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) is an initiative of ISCIII.

Sweden, Karolinska Institutet, Stockholm: The Swedish Twin Registry is supported by the Swedish Department of Higher Education. The STR was supported by grants from the Ministry for Higher Education, the Swedish Research Council (M-2005-1112 and 2009-2298), GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254), NIH Grant DK U01-066134, The Swedish Foundation for Strategic Research (SSF; ICA08-0047), the Swedish Heart-Lung Foundation, the Royal Swedish Academy of Science, and ENGAGE (within the European Union Seventh Framework Programme, HEALTH-F4-2007-201413).

United Kingdom, King’s College London: Financial support was received from the European Union (Framework-V Multicentre Research Grant, QLK1–1999-916), a Multicentre EU Marie Curie Research Training Network Grant, INTACT (MRTN-CT-2006-035988) and a Marie-Curie Intra-European Fellowship (FP-7-People-2009-IEF, No. 254774). Oliver Davis is supported by a Sir Henry Wellcome Fellowship from the Wellcome Trust (WT088984). Cathryn Lewis is partly supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King’s College London.

United States, McLean Hospital/Harvard Medical School, Cambridge, MA: The collection of DNA from participants at the McLean Hospital/Harvard Medical School site was supported in part by an investigator-initiated grant from Ortho-McNeil Janssen Scientific Affairs (principal investigator: Dr Hudson).

United States, University of North Carolina: Sample collection was funded by a grant from the Foundation of Hope, Raleigh, North Carolina. Sara Trace, Jin Szatkiewicz and Jessica Baker were funded by T32 MH076694 (PI: Bulik). Sara Trace was funded by a 2012–2015 Hilda and Preston Davis Foundation Postdoctoral Fellowship Program in Eating Disorders Research Award. Stephanie Zerwas was funded by a UNC BIRWCH award K12HD001441. The Clinical and Translational Science Award (CTSA) program at UNC-Chapel Hill provided additional assistance UL1TR000083.

United States, Vanderbilt University School of Medicine, Nashville TN, and the Kartini Clinic for Disordered Eating, Portland, OR: Cases were ascertained from the Kartini Clinic, Portland Oregon. Sample collection and processing was funded by a Bristol-Myers Squibb Freedom to Discover Unrestricted Metabolic Diseases Research grant to RDC.

ACKNOWLEDGMENTS FOR REPLICATION SAMPLES

Children’s Hospital of Philadelphia/Price Foundation: We gratefully thank all the patients and their families who were enrolled in this study, as well as all the control subjects who donated blood samples to Children’s Hospital of Philadelphia (CHOP) for genetic research purposes. We thank the Price Foundation for their support of the Collaborative Group effort that was responsible for recruitment of patients, collection of clinical information and provision of the DNA samples used in this study. We also thank the Klarman Family Foundation for supporting the study. We thank the technical staff at the Center for Applied Genomics at CHOP for producing the genotypes used for analyses and the nursing, medical assistant and medical staff for their invaluable help with sample recruitments. CTB and NJS are funded in part by the Scripps Translational Sciences Institute Clinical Translational Science Award (Grant Number U54 RR0252204-01). All genome-wide genotyping was funded by an Institute Development Award to the Center for Applied Genomics from the CHOP. 2011–2014 Davis Foundation Postdoctoral Fellowship Program in Eating Disorders Research Award, Yiran Guo; 2012–2015 Davis Foundation Postdoctoral Fellowship Program in Eating Disorders Research Award, Dong Li.

Estonia, Estonian Genome Center of the University of Tartu (EGCUT): EGCUT received targeted financing from Estonian Government SF0180142s08, Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG). We acknowledge EGCUT technical personnel, especially Mr V Soo and S Smit. Data analyses were carried out in part in the High Performance Computing Center of University of Tartu.

Japan, National Institute of Mental Health, National Center of Neurology and Psychiatry: The data and sample collection have been supported by Grants-in-Aid for Scientific Research 20390201 and 23390201 to G Komaki from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. We are indebted to the members of the Japanese Genetic Research Group For Eating Disorders for their contribution of time and effort in collecting samples and clinical data.

The Price Foundation Collaborative Group: Harry Brandt, Steve Crawford, Scott Crow, Manfred M Fichter, Katherine A Halmi, Craig Johnson, Allan S Kaplan, Maria La Via, James Mitchell, Michael Strober, Alessandro Rotondo, Janet Treasure, D Blake Woodside, Cynthia M Bulik, Pamela Keel, Kelly L Klump, Lisa Lilenfeld, Laura M Thornton, Kathy Plotnicov, Andrew W Bergen, Wade Berrettini, Walter Kaye and Pierre Magistretti.

ACKNOWLEDGMENTS FOR CONTROLS

Austria: Controls in Vienna were collected with support to Harald Aschauer by Österreichische Nationalbank (ÖNB Project No. 5777 and 13198), Austrian Science Fund (Project No. P7639), European Science Foundation (ESF Programme MNMI) and European Commission (Biomed 1, J1182E25A).

Canada: NIH Grant No. U24 CA074783 to S Gallinger. This work was made possible through collaboration and cooperative agreements with the Colon Cancer Family Registry and PIs. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating institutions or investigators in the Colon CFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the Colon CFR.

Czech Republic: Support came from the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101).

dbGAP DAC: Research support to collect data and develop an application to support this project was provided by 3P50CA093459, 5P50CA097007, 5R01ES011740 and 5R01CA133996.

Germany: We thank all probands from the community-based cohorts of PopGen, KORA and the Heinz Nixdorf Recall (HNR) study. This study was supported by the German Federal Ministry of Education and Research (BMBF), within the context of the National Genome Research Network plus (NGFNplus), and the MooDS-Net (Grant 01GS08144 to SC). The KORA research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the BMBF and by the State of Bavaria. The Heinz Nixdorf Recall cohort was established with the support of the Heinz Nixdorf Foundation.

Greece: This research has been co-financed by the European Union (European Social Fund –ESF) and Greek national funds through the Operational Program ‘Education and Lifelong Learning’ of the National Strategic Reference Framework (NSRF)—Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund.

Italy (North), Verona: The INCIPE study was co-sponsored by Fondazione Cassa di Risparmio di Verona, Azienda Ospedaliera di Verona, and University of Verona. Samples were collected in Verona, Padua, Monselice and Dolo. Co-principal investigators were Antonio Lupo and Giovanni Gambaro.

Netherlands: Genotyping of controls was funded by NIH/NIMH R01 MH078075, granted to Roel Ophoff.

Sweden: The Swedish Research Council (2006-7481 and 2009-6189), and the Swedish Council of Working Life and Social Research (2008-0567).

Author information

Author notes

  1. V Boraska, C S Franklin, J A B Floyd and L M Thornton: These authors contributed equally to this work.

  2. See Appendix.

  3. X Estivill and A Hinney: These authors contributed equally to this work.

  4. P F Sullivan, D A Collier, E Zeggini and C M Bulik: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    V Boraska, C S Franklin, J A B Floyd, L M Huckins, L Southam, N W Rayner, I Tachmazidou, N Soranzo, A Palotie, C Finan, D W Logan, L Peltonen, G R S Ritchie, J C Barrett & E Zeggini

  2. University of Split School of Medicine, Split, Croatia

    V Boraska

  3. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, UK

    J A B Floyd

  4. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    L M Thornton, F Tozzi, J H Baker, C E Hilliard, C Taico, S Zerwas, S E Trace, Z Yilmaz, P F Sullivan & C M Bulik

  5. Wellcome Trust Centre for Human Genetics (WTCHG), University of Oxford, Oxford, UK

    N W Rayner

  6. Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Oxford, UK

    N W Rayner

  7. Department of Psychology, Michigan State University, East Lansing, MI, USA

    K L Klump

  8. Section of Eating Disorders, Institute of Psychiatry, King’s College London, London, UK

    J Treasure & U Schmidt

  9. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK

    C M Lewis, O S P Davis, S Helder, G Breen, S Cohen-Woods, A Farmer, P McGuffin, G Kalsi, M Roberts & D A Collier

  10. Health Services Research Unit, University of Aberdeen, Aberdeen, UK

    K Kiezebrink

  11. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany

    J Hebebrand, S Scherag & A Hinney

  12. INSERM U894, Centre of Psychiatry and Neuroscience, Paris, France

    P Gorwood, C Boni, N Ramoz & A Versini

  13. Sainte-Anne Hospital (CMME), University of Paris-Descartes, Paris, France

    P Gorwood

  14. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    R A H Adan, M J H Kas, M K Brandys & J Hendriks

  15. Altrecht Eating Disorders Rintveld, Zeist, The Netherlands

    R A H Adan, M K Brandys, U N Danner & A A van Elburg

  16. Department of Neurosciences, University of Padova, Padova, Italy

    A Favaro, P Santonastaso, D Degortes & E Tenconi

  17. Department of Psychiatry and CIBERON, University Hospital of Bellvitge-IDIBELL, Barcelona, Spain

    F Fernández-Aranda & S Jiménez-Murcia

  18. Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain

    F Fernández-Aranda & S Jiménez-Murcia

  19. Genomics and Disease Group, Centre for Genomic Regulation (CRG), Barcelona, Spain

    M Gratacos, E Docampo, G Escaramís, R Rabionet & X Estivill

  20. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    M Gratacos, E Docampo, G Escaramís, R Rabionet & X Estivill

  21. Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    M Gratacos, E Docampo, G Escaramís, R Rabionet & X Estivill

  22. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    M Gratacos, E Docampo, G Escaramís, R Rabionet & X Estivill

  23. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland

    F Rybakowski

  24. Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland

    M Dmitrzak-Weglarz, A Slopien & J Hauser

  25. Hjelt Institute, University of Helsinki, Helsinki, Finland

    J Kaprio, A Keski-Rahkonen & A Raevuori

  26. Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland

    J Kaprio

  27. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland

    J Kaprio

  28. Department of Adolescent Psychiatry, Helsinki University Central Hospital, Helsinki, Finland

    A Raevuori

  29. Center for Eating Disorders Ursula, Leidschendam, The Netherlands

    E F Van Furth & M C T Slof-Op 't Landt

  30. Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands

    E F Van Furth

  31. Department of Medical Statistics, Molecular Epidemiology Section, Leiden University Medical Centre, Leiden, The Netherlands

    M C T Slof-Op 't Landt, I Meulenbelt & P E Slagboom

  32. Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA, USA

    J I Hudson

  33. Department of Genetics, Environment and Mental Health, Norwegian Institute of Public Health, Oslo, Norway

    T Reichborn-Kjennerud & G P S Knudsen

  34. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    T Reichborn-Kjennerud

  35. Department of Psychiatry, University of Naples SUN, Naples, Italy

    P Monteleone, A Tortorella & M Maj

  36. Chair of Psychiatry, University of Salerno, Salerno, Italy

    P Monteleone

  37. Centre for Addiction and Mental Health, Toronto, ON, Canada

    A S Kaplan, J L Kennedy, R D Levitan & Z Yilmaz

  38. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    A S Kaplan, J L Kennedy & R D Levitan

  39. Department of Child and Adolescent Psychiatry, Eating Disorders Unit, Medical University of Vienna, Vienna, Austria

    A Karwautz, J Huemer, D Koubek, E Merl & G Wagner

  40. The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    H Hakonarson, Y Guo & D Li

  41. The Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    H Hakonarson

  42. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    W H Berrettini

  43. Department of Molecular and Experimental Medicine and The Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA, USA

    N J Schork

  44. Department of Psychosomatic Research, National Institute of Mental Health, NCNP, Tokyo, Japan

    G Komaki & T Ando

  45. School of Health Sciences at Fukuoka, International University of Health and Welfare, Fukuoka, Japan

    G Komaki

  46. Department of Molecular Life Sciences, Tokai University School of Medicine, Kanagawa, Japan

    H Inoko

  47. Estonian Genome Center, University of Tartu, Tartu, Estonia

    T Esko, K Fischer & A Metspalu

  48. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    K Männik & A Metspalu

  49. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

    K Männik

  50. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    R D Cone

  51. Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    J Dackor, J P Szatkiewicz & P F Sullivan

  52. Seattle University College of Nursing, Seattle, WA, USA

    J E DeSocio

  53. Kartini Clinic, Portland, OR, USA

    J K O'Toole

  54. Centre de Psychiatrie et Neurosciences - Inserm U894, Paris, France

    J Pantel

  55. Department of Genetics, Evolution and Environment, University College London, UCL Genetics Institute, London, UK

    O S P Davis

  56. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Clinics RWTH Aachen, Aachen, Germany

    K Bühren & B Herpertz-Dahlmann

  57. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité, Berlin, Germany

    R Burghardt

  58. Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany

    M de Zwaan

  59. Department of Psychosomatic Medicine and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany

    M de Zwaan

  60. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Würzburg, Würzburg, Germany

    K Egberts

  61. Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

    S Ehrlich

  62. Athinoula A. Martinos Center for Biomedical Imaging, Psychiatric Neuroimaging Research Program, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, USA

    S Ehrlich

  63. Departments of Psychosocial and Internal Medicine, Heidelberg University, Heidelberg, Germany

    W Herzog

  64. Parklandklinik, Bad Wildungen, Germany

    H Imgart

  65. Institute for Medical Informatics, Biometry and Epidemiology, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany

    A Scherag

  66. Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tübingen, Tübingen, Germany

    S Zipfel

  67. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    C de Kovel, B P C Koeleman & E Strengman

  68. Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA

    R A Ophoff

  69. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center, Utrecht, Utrecht, The Netherlands

    R A Ophoff

  70. Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands

    A A van Elburg

  71. Department of Woman and Child Health, Clinical Genetics Unit, University of Padova, Padova, Italy

    A Bruson, M Clementi & M Forzan

  72. M. Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland

    J Lissowska

  73. Department of Epidemiology, Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland

    A Rajewski & N Szeszenia-Dabrowska

  74. Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    L Karhunen

  75. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, The Netherlands

    P E Slagboom

  76. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece

    G Dedoussis, K Tziouvas & I Ntalla

  77. 1st Department of Psychiatry, Athens University Medical School, Athens, Greece

    D Dikeos

  78. 1st Department of Psychiatry, Eating Disorders Unit, Athens University Medical School, Athens, Greece

    F Gonidakis

  79. 2nd Department of Pediatrics – Medical School, Adolescent Health Unit (A.H.U.), University of Athens ‘P. & A. Kyriakou’ Children’s Hospital, Athens, Greece

    A Tsitsika

  80. Department of Psychiatry, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    H Papezova & D Martaskova

  81. Department of Pediatrics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    L Slachtova

  82. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    P Lichtenstein

  83. Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany

    S Cichon & S Herms

  84. Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany

    S Cichon

  85. Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland

    S Cichon & S Herms

  86. Klinikum der Medizinischen Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany

    I Giegling & D Rujescu

  87. Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany

    S Schreiber

  88. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    H-E Wichmann

  89. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany

    H-E Wichmann

  90. CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France

    C Dina

  91. McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada

    R Sladek

  92. Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus-Gemelly Hospitals, Catholic University, Rome, Italy

    G Gambaro

  93. Unitat de Recerca de Reumatologia (URR), Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona, Spain

    A Julia & S Marsal

  94. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France

    V Gaborieau

  95. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    D M Dick

  96. The Finnish Institute of Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    A Palotie, S Ripatti & E Widén

  97. The Program for Human and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA

    A Palotie

  98. Finnish Institute of Occupational Health, Helsinki, Finland

    S Ripatti & E Widén

  99. Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    O A Andreassen, T Espeseth & M Mattingsdal

  100. Department of Psychology, University of Oslo, Oslo, Norway

    T Espeseth & I Reinvang

  101. Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway

    A Lundervold

  102. Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway

    A Lundervold

  103. K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway

    A Lundervold

  104. Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway

    V M Steen & S Le Hellard

  105. Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    V M Steen & S Le Hellard

  106. Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    V Bencko

  107. Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    L Foretova & M Navratilova

  108. Palacky University, Olomouc, Czech Republic

    V Janout

  109. University Health Network, Toronto General Hospital, Toronto, ON, Canada

    S Gallinger

  110. Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, ON, Canada

    S Gallinger

  111. Departments of Psychiatry, and Genetics and Genomic Sciences, Seaver Autism Center, and the Mindich Child Health and Development Institute, Mount Sinai School of Medicine, New York, NY, USA

    D Pinto

  112. The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada

    S W Scherer

  113. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

    H Aschauer, L Carlberg & A Schosser

  114. The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    L Alfredsson & B Ding

  115. Department of Medicine at the Karolinska University Hospital, Rheumatology Unit, Solna, Sweden

    L Klareskog & L Padyukov

  116. Inserm, U1061, Université Montpellier 1, Montpellier, France

    P Courtet, S Guillaume & I Jaussent

  117. Department of Emergency Psychiatry, CHU Montpellier, Montpellier, France

    P Courtet, S Guillaume & I Jaussent

  118. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge

    G R S Ritchie

  119. Eli Lilly and Company, Erl Wood Manor, Windlesham, UK

    D A Collier

  120. Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    C M Bulik

Authors
  1. V Boraska
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  2. C S Franklin
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  33. P Monteleone
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  34. A S Kaplan
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  39. D Li
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  41. G Komaki
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  42. T Ando
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Consortia

The Wellcome Trust Case Control Consortium 322

  • Carl A Anderson
  • , Jeffrey C Barrett
  • , James A B Floyd
  • , Christopher S Franklin
  • , Ralph McGinnis
  • , Nicole Soranzo
  • , Eleftheria Zeggini
  • , Jennifer Sambrook
  • , Jonathan Stephens
  • , Willem H Ouwehand
  • , Wendy L McArdle
  • , Susan M Ring
  • , David P Strachan
  • , Graeme Alexander
  • , Cynthia M Bulik
  • , David A Collier
  • , Peter J Conlon
  • , Anna Dominiczak
  • , Audrey Duncanson
  • , Adrian Hill
  • , Cordelia Langford
  • , Graham Lord
  • , Alexander P Maxwell
  • , Linda Morgan
  • , Leena Peltonen
  • , Richard N Sandford
  • , Neil Sheerin
  • , Nicole Soranzo
  • , Fredrik O Vannberg
  • , Jeffrey C Barrett
  • , Hannah Blackburn
  • , Wei-Min Chen
  • , Sarah Edkins
  • , Mathew Gillman
  • , Emma Gray
  • , Sarah E Hunt
  • , Cordelia Langford
  • , Suna Onengut-Gumuscu
  • , Simon Potter
  • , Stephen S Rich
  • , Douglas Simpkin
  •  & Pamela Whittaker

Corresponding author

Correspondence to C M Bulik.

Ethics declarations

Competing interests

Patrick F Sullivan was on the SAB of Expression Analysis (Durham, NC, USA). Cynthia Bulik was a consultant for Shire Pharmaceuticals at the time the manuscript was written. Federica Tozzi was a full-time employee of GSK at the time when the study was performed. David A Collier was employed by Eli Lilly, UK for a portion of the time that this study was performed. James L Kennedy has received honoraria from Eli Lilly and Roche. Robert D Levitan has received honorarium from Astra-Zeneca. The remaining authors declare no conflict of interest.

Additional information

WELLCOME TRUST SANGER INSTITUTE: THE WTCCC3 Data Analysis Group: Carl A Anderson1, Jeffrey C Barrett1, James AB Floyd1, Christopher S Franklin1, Ralph McGinnis1, Nicole Soranzo1, Eleftheria Zeggini1. UK Blood Services Controls: Jennifer Sambrook2, Jonathan Stephens2, Willem H Ouwehand2. 1958 Birth Cohort Controls: Wendy L McArdle3, Susan M Ring3, David P Strachan4. Management Committee: Graeme Alexander5, Cynthia M Bulik6, David A Collier7, Peter J Conlon8, Anna Dominiczak9, Audrey Duncanson10, Adrian Hill11, Cordelia Langford1, Graham Lord12, Alexander P Maxwell13, Linda Morgan14, Leena Peltonen1, Richard N Sandford15, Neil Sheerin12, Nicole Soranzo1, Fredrik O Vannberg11, Jeffrey C Barrett1 (chair). DNA, Genotyping, and Informatics Group: Hannah Blackburn1, Wei-Min Chen16, Sarah Edkins1, Mathew Gillman1, Emma Gray1, Sarah E Hunt1, Cordelia Langford1, Suna Onengut-Gumuscu16, Simon Potter1, Stephen S Rich16, Douglas Simpkin1, Pamela Whittaker1.

Supplementary Information accompanies the paper on the Molecular Psychiatry website

APPENDIX

WELLCOME TRUST SANGER INSTITUTE: THE WTCCC3

Data Analysis Group: Carl A Anderson1, Jeffrey C Barrett1, James AB Floyd1, Christopher S Franklin1, Ralph McGinnis1, Nicole Soranzo1, Eleftheria Zeggini1.

UK Blood Services Controls: Jennifer Sambrook2, Jonathan Stephens2, Willem H Ouwehand2.

1958 Birth Cohort Controls: Wendy L McArdle3, Susan M Ring3, David P Strachan4.

Management Committee: Graeme Alexander5, Cynthia M Bulik6, David A Collier7, Peter J Conlon8, Anna Dominiczak9, Audrey Duncanson10, Adrian Hill11, Cordelia Langford1, Graham Lord12, Alexander P Maxwell13, Linda Morgan14, Leena Peltonen1, Richard N Sandford15, Neil Sheerin12, Nicole Soranzo1, Fredrik O Vannberg11, Jeffrey C Barrett1 (chair).

DNA, Genotyping, and Informatics Group: Hannah Blackburn1, Wei-Min Chen16, Sarah Edkins1, Mathew Gillman1, Emma Gray1, Sarah E Hunt1, Cordelia Langford1, Suna Onengut-Gumuscu16, Simon Potter1, Stephen S Rich16, Douglas Simpkin1, Pamela Whittaker1.

  1. 1

    The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK

  2. 2

    Division of Transfusion Medicine, Department of Haematology, University of Cambridge, NHSBT Cambridge Centre, Long Road, Cambridge, CB2 0PT, UK

  3. 3

    Department of Social Medicine, University of Bristol, Bristol BS8 2BN, UK

  4. 4

    St. George’s University, Division of Community Health Sciences, London SW19 0RE, UK

  5. 5

    Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK

  6. 6

    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

  7. 7

    Institute of Psychiatry, King’s College London, London SE5 8AF

  8. 8

    Department of Nephrology, Beaumont Hospital, Dublin, Ireland; and Royal College of Surgeons Dublin, Dublin, Ireland

  9. 9

    BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK

  10. 10

    Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK

  11. 11

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JA, UK

  12. 12

    MRC Centre for Transplantation, King’s College London, London SE1 9RT, UK

  13. 13

    Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK

  14. 14

    School of Molecular Medical Sciences, University of Nottingham, Nottingham NG7 2UH, UK

  15. 15

    Academic Department of Medical Genetics, Cambridge University, Cambridge CB2 0QQ, UK

  16. 16

    Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

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Boraska, V., Franklin, C., Floyd, J. et al. A genome-wide association study of anorexia nervosa. Mol Psychiatry 19, 1085–1094 (2014). https://doi.org/10.1038/mp.2013.187

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  • DOI: https://doi.org/10.1038/mp.2013.187

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