Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Hunna J. Watson, Laura M. Thornton, Zeynep Yilmaz, Jessica H. Baker, Jonathan RI. Coleman, Roger AH. Adan, Lars Alfredsson, Ole A. Andreassen, Helga Ask, Wade H. Berrettini, Michael Boehnke, Ilka Boehm, Claudette Boni, Katharina Buehren, Josef Bulant, Roland Burghardt, Xiao Chang, Sven Cichon, Roger D. Cone, Philippe CourtetScott Crow, James J. Crowley, Unna N. Danner, Martina de Zwaan, George Dedoussis, Janiece E. DeSocio, Danielle M. Dick, Dimitris Dikeos, Christian Dina, Srdjan Djurovic, Monika Dmitrzak-Weglarz, Elisa Docampo-Martinez, Philibert Duriez, Karin Egberts, Stefan Ehrlich, Johan G. Eriksson, Geòrgia Escaramís, Tõnu Esko, Xavier Estivill, Anne Farmer, Fernando Fernández-Aranda, Manfred M. Fichter, Manuel Föcker, Lenka Foretova, Andreas J. Forstner, Oleksandr Frei, Steven Gallinger, Ina Giegling, Johanna Giuranna, Fragiskos Gonidakis, Philip Gorwood, Mònica Gratacòs, Sébastien Guillaume, Yiran Guo, Hakon Hakonarson, Joanna Hauser, Alexandra Havdahl, Johannes Hebebrand, Sietske G. Helder, Stefan Herms, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, James I. Hudson, Hartmut Imgart, Stephanie Jamain, Vladimir Janout, Susana Jiménez-Murcia, Ian R. Jones, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Martien JH. Kas, Pamela K. Keel, James L. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Lars Klareskog, Kelly L. Klump, Gun Peggy S. Knudsen, Maria C. La Via, Stephanie Le Hellard, Marion Leboyer, Dong Li, Lisa Lilenfeld, Bochao Lin, Jolanta Lissowska, Jurjen Luykx, Pierre Magistretti, Mario Maj, Sara Marsal, Christian R. Marshall, Morten Mattingsdal, Ingrid Meulenbelt, Nadia Micali, Karen S. Mitchell, Alessio Maria Monteleone, Palmiero Monteleone, Richard Myers, Marie Navratilova, Ionna Ntalla, Julie K. O'Toole, Roel A. Ophoff, Leonid Padyukov, Jacques Pantel, Hana Papežová, Dalila Pinto, Anu Raevuori, Nicolas Ramoz, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Stephan Ripke, Franziska Ritschel, Marion Roberts, Alessandro Rotondo, Dan Rujescu, Filip Rybakowski, André Scherag, Stephen W. Scherer, Ulrike Schmidt, Laura J. Scott, Jochen Seitz, Yasmina Silén, Lenka Šlachtová, P. Eline Slagboom, Margarita CT. Slof-Op 't Landt, Agnieszka Slopien, Sandro Sorbi, Beata Świątkowska, Alfonso Tortorella, Federica Tozzi, Janet Treasure, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Esther Walton, Elisabeth Widen, 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, Scott Gordon, Sarah Maguire, Janne T. Larsen, Richard Parker, Liselotte V. Petersen, Jennifer Jordan, Martin Kennedy, Tracey D. Wade, Andreas Birgegård, Paul Lichtenstein, Mikael Landén, Nicholas G. Martin, Preben Bo Mortensen, Gerome Breen, Cynthia M. Bulik

Research output: Contribution to journalArticlepeer-review

Abstract

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.
Original languageEnglish
JournalBiological Psychiatry Global Open Science
Early online date20 Sep 2021
DOIs
Publication statusE-pub ahead of print - 20 Sep 2021

Keywords

  • age at onset
  • anorexia nervosa
  • early-onset
  • genetics
  • genetic risk score
  • GWAS
  • menarche
  • Mendelian randomization
  • puberty

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