Common Genetic Variation and Age of Onset of Anorexia Nervosa

Hunna J. Watson, Laura M. Thornton, Zeynep Yilmaz, Jessica H. Baker, Jonathan R.I. Coleman, Roger A.H. 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, Dong Li, Pierre Magistretti, Nicholas G. Martin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of 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 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of 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 (single nucleotide polymorphism–h2) were 0.01–0.04 for age of 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 of onset and early-onset AN estimated from independent GWASs significantly predicted age of 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 of onset and implicate biological pathways regulating menarche and reproduction.

Original languageEnglish (US)
Pages (from-to)368-378
Number of pages11
JournalBiological Psychiatry Global Open Science
Issue number4
StatePublished - Oct 2022


  • Age of onset
  • Anorexia nervosa
  • Early-onset
  • Genetic risk score
  • Genetics
  • GWAS
  • Menarche
  • Mendelian randomization
  • Puberty

ASJC Scopus subject areas

  • Phychiatric Mental Health
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry


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