A genome-wide association study of anorexia nervosa View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-10

AUTHORS

V Boraska, C S Franklin, J A B Floyd, L M Thornton, L M Huckins, L Southam, N W Rayner, I Tachmazidou, K L Klump, J Treasure, C M Lewis, U Schmidt, F Tozzi, K Kiezebrink, J Hebebrand, P Gorwood, R A H Adan, M J H Kas, A Favaro, P Santonastaso, F Fernández-Aranda, M Gratacos, F Rybakowski, M Dmitrzak-Weglarz, J Kaprio, A Keski-Rahkonen, A Raevuori, E F Van Furth, M C T Slof-Op 't Landt, J I Hudson, T Reichborn-Kjennerud, G P S Knudsen, P Monteleone, A S Kaplan, A Karwautz, H Hakonarson, W H Berrettini, Y Guo, D Li, N J Schork, G Komaki, T Ando, H Inoko, T Esko, K Fischer, K Männik, A Metspalu, J H Baker, R D Cone, J Dackor, J E DeSocio, C E Hilliard, J K O'Toole, J Pantel, J P Szatkiewicz, C Taico, S Zerwas, S E Trace, O S P Davis, S Helder, K Bühren, R Burghardt, M de Zwaan, K Egberts, S Ehrlich, B Herpertz-Dahlmann, W Herzog, H Imgart, A Scherag, S Scherag, S Zipfel, C Boni, N Ramoz, A Versini, M K Brandys, U N Danner, C de Kovel, J Hendriks, B P C Koeleman, R A Ophoff, E Strengman, A A van Elburg, A Bruson, M Clementi, D Degortes, M Forzan, E Tenconi, E Docampo, G Escaramís, S Jiménez-Murcia, J Lissowska, A Rajewski, N Szeszenia-Dabrowska, A Slopien, J Hauser, L Karhunen, I Meulenbelt, P E Slagboom, A Tortorella, M Maj, G Dedoussis, D Dikeos, F Gonidakis, K Tziouvas, A Tsitsika, H Papezova, L Slachtova, D Martaskova, J L Kennedy, R D Levitan, Z Yilmaz, J Huemer, D Koubek, E Merl, G Wagner, P Lichtenstein, G Breen, S Cohen-Woods, A Farmer, P McGuffin, S Cichon, I Giegling, S Herms, D Rujescu, S Schreiber, H-E Wichmann, C Dina, R Sladek, G Gambaro, N Soranzo, A Julia, S Marsal, R Rabionet, V Gaborieau, D M Dick, A Palotie, S Ripatti, E Widén, O A Andreassen, T Espeseth, A Lundervold, I Reinvang, V M Steen, S Le Hellard, M Mattingsdal, I Ntalla, V Bencko, L Foretova, V Janout, M Navratilova, S Gallinger, D Pinto, S W Scherer, H Aschauer, L Carlberg, A Schosser, L Alfredsson, B Ding, L Klareskog, L Padyukov, P Courtet, S Guillaume, I Jaussent, C Finan, G Kalsi, M Roberts, D W Logan, L Peltonen, G R S Ritchie, J C Barrett, The Wellcome Trust Case Control Consortium, 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, Fredrik O Vannberg, Hannah Blackburn, Wei-Min Chen, Sarah Edkins, Mathew Gillman, Emma Gray, Sarah E Hunt, Suna Onengut-Gumuscu, Simon Potter, Stephen S Rich, Douglas Simpkin, Pamela Whittaker, X Estivill, A Hinney, P F Sullivan, D A Collier, E Zeggini, C M Bulik

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. More... »

PAGES

1085

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  • Journal

    TITLE

    Molecular Psychiatry

    ISSUE

    10

    VOLUME

    19

    Author Affiliations

  • University of Split
  • Wellcome Sanger Institute
  • Queen Mary University of London
  • University of North Carolina at Chapel Hill
  • Oxford Centre for Diabetes, Endocrinology and Metabolism
  • Michigan State University
  • King's College London
  • University of Aberdeen
  • Paris Descartes University
  • University Medical Center Utrecht
  • University of Padua
  • University of Barcelona
  • Institut Hospital del Mar d'Investigacions Mèdiques
  • Institute of Psychiatry and Neurology
  • Poznan University of Medical Sciences
  • National Institute for Health and Welfare
  • University of Helsinki
  • Helsinki University Central Hospital
  • Leiden University Medical Center
  • University of Oslo
  • Norwegian Institute of Public Health
  • University of Salerno
  • University of Toronto
  • Medical University of Vienna
  • University of Pennsylvania
  • Children's Hospital of Philadelphia
  • Scripps Research Institute
  • International University of Health and Welfare
  • National Institute of Mental Health
  • Tokai University
  • University of Tartu
  • University of Lausanne
  • Vanderbilt University
  • Seattle University
  • Centre for Psychiatry and Neuroscience
  • University College London
  • RWTH Aachen University
  • Charité
  • University of Erlangen-Nuremberg
  • University of Würzburg
  • Massachusetts General Hospital
  • Heidelberg University
  • Centrum Onkologii Instytut
  • Nofer Institute of Occupational Medicine
  • University of Eastern Finland
  • University of Naples Federico II
  • Harokopio University
  • National and Kapodistrian University of Athens
  • Panagiotis & Aglaia Kyriakou Children's Hospital
  • Charles University
  • Centre for Addiction and Mental Health
  • Karolinska Institute
  • University of Basel
  • Martin Luther University Halle-Wittenberg
  • Kiel University
  • Ludwig Maximilian University of Munich
  • Pasteur Institute of Lille
  • McGill University and Génome Québec Innovation Centre
  • Catholic University of the Sacred Heart
  • Hospital Universitari Vall d'Hebron
  • International Agency For Research On Cancer
  • Virginia Commonwealth University
  • Broad Institute
  • Finnish Institute of Occupational Health
  • University of Bergen
  • Haukeland University Hospital
  • Masaryk Memorial Cancer Institute
  • Palacký University, Olomouc
  • Lunenfeld-Tanenbaum Research Institute
  • Icahn School of Medicine at Mount Sinai
  • Hospital for Sick Children
  • University Hospital of Montpellier
  • European Bioinformatics Institute
  • Eli Lilly (United Kingdom)
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/mp.2013.187

    DOI

    http://dx.doi.org/10.1038/mp.2013.187

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041076958

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24514567


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    98 schema:description 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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