A genome-wide association study of anorexia nervosa

Boraska, Vesna and Franklin, Christopher S. and Floyd, James A.B. and Thornton, Laura M. and Huckins, Laura M. and Southam, Lorraine and Rayner, N. William and Tachmazidou, Ioanna and Klumpp, Kelly and Treasure, Janet and Lewis, Cathryn M. and Schmidt, Ulrike and Tozzi, Federica and Kiezebrink, Kirsty and Hebebrand, Johannes and Gorwood, Philip and Adan, Roger A. H. and Kas, Martin J. H. and Favaro, Angela and Santonastaso, Paolo and Fernández-Aranda, Fernando and Gratacòs, Mònica and Rybakowski, Filip and Dmitrzak-Weglarz, Monika and Kaprio, Jaakko and Keski-Rahkonen, Anna and Raevuori, Anu and Van Furth, Eric F. and Slof-Op 't Landt, Margarita and Hudson, James I. and Reichborn-Kjennerud, Ted and Knudsen, Gun Peggy S. and Monteleone, Palmiero and Kaplan, Allan S. and Karwautz, Andreas and Hakonarson, Hakon and Berrettini, Wade H. and Guo, Yiran and Li, Dong and Schork, Nicholas and Komaki, Gen and Ando, Tetsuya and Inoko, Hidetoshi and Esko, Tõnu and Fischer, Krista and Männik, Katrin and Metspalu, Andres and Baker, Jessica H. and Cone, Roger D. and Dackor, Jennifer and DeSocio, Janiece E. and Hilliard, Christopher E. and O'Toole, Julie K. and Pantel, Jacques and Szatkiewicz, Jin P. and Taico, Chrysecolla and Zerwas, Stephanie and Trace, Sara E. and Davis, Oliver S. P. and Helder, Sietske and Buhren, Katherina and Burghardt, Roland and de Zwaan, Martina and Egberts, Karin and Ehrlich, Stefan and Herpertz-Dahlmann, Beate and Herzog, Wolfgang and Imgart, Hartmut and Scherag, André and Scherag, Susann and Zipfel, Stephan and Boni, Claudette and Ramoz, Nicolas and Versini, Audrey and Brandys, Marek K. and Danner, Unna N. and de Kovel, Carolien and Hendriks, Judith and Koeleman, Bobby P. C. and Ophoff, Roel A. and Strengman, Eric and van Elburg, Annemarie A. and Bruson, Alice and Clementi, Maurizio and Degortes, Daniela and Forzan, Monica and Tenconi, Elena and Docampo, Elisa and Escaramis, Georgia and Jiménez-Murcia, Susana and Lissowska, Jolanta and Rajewski, Andrzej and Szeszenia-Dabrowska, Neonila and Slopien, Agnieszka and Hauser, Joanna and Karhunen, Leila and Meulenbelt, Ingrid and Slagboom, P. Eline and Tortorella, Alfonso and Maj, Mario and Dedoussis, George and Dikeos, Dimitris and Gonidakis, Fragiskos and Tziouvas, Konstantinos and Tsitsika, Artemis and Papezova, Hana and Slachtova, Lenka and Martaskova, Debora and Kennedy, James L. and Levitan, Robert D. and Yilmaz, Zeynep and Huemer, Julia and Koubek, Doris and Merler, Elisabeth and Wagner, Gudrun and Lichtenstein, Paul and Breen, Gerome and Cohen-Woods, Sarah and Farmer, Ann and McGuffin, Peter and Cichon, Sven and Giegling, Ina and Herms, Stefan and Rujescu, Dan and Schreiber, Stefan and Wichmann, H-Erich and Dina, Christian and Sladek, Rob and Gambaro, Giovanni and Soranzo, Nicole and Julia, Antonio and Marsal, Sara and Rabionet, Raquel and Gaborieau, Valerie and Dick, Danielle M. and Palotie, Aarno and Ripatti, Samuli and Widen, Elisabeth and Andreassen, Ole A. and Espeseth, Thomas and Lundervold, Astri J. and Reinvang, Ivar and Steen, Vidar M. and Le Hellard, Stephanie and Mattingsdal, Morten and Ntalla, Ioanna and Bencko, Vladimir and Foretova, Lenka and Janout, Vladimir and Navratilova, Marie and Gallinger, Steven and Pinto, Dalila and Scherer, Stephen W. and Aschauer, Harald and Carlberg, Laura and Schosser, Alexandra and Alfredsson, Lars and Ding, Bo and Klareskog, Lars and Padyukov, Leonid and Finan, Chris and Guillaume, Phillippe and Kalsi, Gursharan and Roberts, Marion and Logan, Darren W. and Peltonen, Leena and Ritchie, Graham R. S. and Barrett, Jeffrey C. and Wellcome Trust Case Control Consortium, and Estivill, Xavier and Hinney, Anke and Sullivan, Patrik F. and Collier, David A. and Zeggini, Eleftheria and Bulik, Cynthia M.. (2014) A genome-wide association study of anorexia nervosa. Molecular Psychiatry, 19 (10). pp. 1085-1094.

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Official URL: https://edoc.unibas.ch/61529/

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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 x 10(-7)) in SOX2OT and rs17030795 (P=5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 x 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 x 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 x 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:17 Jul 2020 10:11
Deposited On:17 Jul 2020 10:11

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