Common Genetic Variation and Age of Onset of Anorexia Nervosa

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 s...

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Authors: Watson, Hunna J.; Thornton, Laura M.; Yilmaz, Zeynep; Baker, Jessica H.; Coleman, Jonathan R. I.; Adan, Roger A. H.; Alfredsson, Lars; Andreassen, Ole A.; Ask, Helga; Berrettini, Wade H.; Boehnke, Michael; Scherag, André; Scherer, Stephen W.; Schmidt, Ulrike; Scott, Laura J.; Seitz, Jochen; Silén, Yasmina; Slachtova, Lenka; Slagboom, P. Eline; Slof-Op't Landt, Margarita C. T.; Dedoussis, George; Ehrlich, Stefan; Buehren, Katharina; Slopien, Agnieszka; Sorbi, Sandro; Swiqtkowska, Beata; Tortorella, Alfonso; Tozzi, Federica; Treasure, Janet; Tsitsika, Artemis; Tyszkiewicz-Nwafor, Marta; Tziouvas, Konstantinos; Eriksson, Johan G.; DeSocio, Janiece E.; Elburg, Annemarie A. van; Bulant, Josef; Furth, Eric F. van; Walton, Esther; Widen, Elisabeth; Zerwas, Stephanie; Zipfel, Stephan; Bergen, Andrew W.; Boden, Joseph M.; Escaramís Babiano, Geòrgia; Brandt, Harry; Dick, Danielle M.; Crawford, Steven; Halmi, Katherine A.; Burghardt, Roland; Horwood, L. John; Johnson, Craig; Kaplan, Allan S.; Kaye, Walter H.; Mitchell, James E.; Esko, Tõnu; Olsen, Catherine M.; Pearson, John F.; Dikeos, Dimitris; Pedersen, Nancy L.; Strober, Michael; Werge, Thomas; Chang, Xiao; Whiteman, David C.; Woodside, D. Blake; Gordon, Scott; Estivill, Xavier, 1955-; Maguire, Sarah; Larsen, Janne T.; Parker, Richard; Dina, Christian; Petersen, Liselotte Vogdrup; Jordan, Jennifer; Kennedy, Martin; Wade, Tracey D.; Cichon, Sven; Birgegård, Andreas; Farmer, Anne; Lichtenstein, Paul; Landén, Mikael; Martin, Nicholas G.; Mortensen, Preben Bo; Djurovic, Srdjan; Breen, Gerome; Bulik, Cynthia M.; Cone, Roger D.; Courtet, Philippe; Crow, Scott; Fernández Aranda, Fernando; Crowley, James J.; Danner, Unna N.; Dmitrzak-Weglarz, Monika; Docampo Martínez, Elisa; Duriez, Philibert; Monteleone, Palmiero; Egberts, Karin; Fichter, Manfred M.; Föcker, Manuel; Myers, Richard; Ramoz, Nicolás; Foretova, Lenka; Forstner, Andreas J.; Frei, Oleksandr; Gallinger, Steven; Giegling, Ina; Giuranna, Johanna; Gonidakis, Fragiskos; Gorwood, Philip; Gratacòs, Mònica; Guillaume, Sébastien; Reichborn-Kjennerud, Ted; Navratilova, Marie; Guo, Yiran; Hakonarson, Hakon; Hauser, Joanna; Havdahl, Alexandra; Hebebrand, Johannes; Helder, Sietske G.; Herms, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Ricca, Valdo; Hinney, Anke; Ntalla, Ioanna; Hübel, Christopher; Hudson, James I.; Imgart, Hartmut; Jamain, Stephanie; Janout, Vladimir; Jiménez-Murcia, Susana; Jones, Ian R.; Julià, Antonio; Ripatti, Samuli; Kalsi, Gursharan; Kaminská, Deborah; O'Toole, Julie K.; Kaprio, Jaakko; Karhunen, Leila; Kas, Martien J. H.; Keel, Pamela P.; Kennedy, James L.; Keski-Rahkonen, Anna; Kiezebrink, Kirsty; Ripke, Stephan; Klareskog, Lars; Klump, Kelly L.; Knudsen, Gun Peggy S.; Ophoff, Roel A.; Via, Maria C. La; Le Hellard, Stephanie; Leboyer, Marion; Li, Dong; Lilenfeld, Lisa; Lin, Bochao; Ritschel, Franziska; Lissowska, Jolanta; Luykx, Jurjen; Magistretti, Pierre J.; Maj, Mario; Padyukov, Leonid; Marsal Barril, Sara; Marshall, Christian R.; Mattingsdal, Morten; Meulenbelt, Ingrid; Micali, Nadia; Roberts, Marion; Mitchell, Karen S.; Monteleone, Alessio Maria; Pantel, Jacques; Papezova, Hana; Pinto, Dalila; Boehm, Ilka; Raevuori, Anu; Rotondo, Alessandro; Rujescu, Dan; Boni, Claudette; Zwaan, Martina de; Rybakowski, Filip
Format: Article
Status:Published version
Publication date:2022
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/205025
Online Access:https://hdl.handle.net/2445/205025
Access Level:Open access
Keyword:Anorèxia nerviosa
Genètica
Lleis de Mendel
Anorexia nervosa
Genetics
Mendel's law
Summary: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.

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