Common Genetic Variation and Age of Onset of Anorexia Nervosa.
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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, Boehm Ilka, Boni Claudette, Buehren Katharina, Bulant Josef, Burghardt Roland, Chang Xiao, Cichon Sven, Cone Roger D, Courtet Philippe, Crow Scott, Crowley James J, Danner Unna N, de Zwaan Martina, Dedoussis George, DeSocio Janiece E, Dick Danielle M, Dikeos Dimitris, Dina Christian, Djurovic Srdjan, Dmitrzak-Weglarz Monika, Docampo-Martinez Elisa, Duriez Philibert, Egberts Karin, Ehrlich Stefan, Eriksson Johan G, Escaramís Geòrgia, Esko Tõnu, Estivill Xavier, Farmer Anne, Fernández-Aranda Fernando, Fichter Manfred M, Föcker Manuel, Foretova Lenka, Forstner Andreas J, Frei Oleksandr, Gallinger Steven, Giegling Ina, Giuranna Johanna, Gonidakis Fragiskos, Gorwood Philip, Gratacòs Mònica, Guillaume Sébastien, Guo Yiran, Hakonarson Hakon, Hauser Joanna, Havdahl Alexandra, Hebebrand Johannes, Helder Sietske G, Herms Stefan, Herpertz-Dahlmann Beate, Herzog Wolfgang, Hinney Anke, Hübel Christopher, Hudson James I, Imgart Hartmut, Jamain Stephanie, Janout Vladimir, Jiménez-Murcia Susana, Jones Ian R, Julià Antonio, Kalsi Gursharan, Kaminská Deborah, Kaprio Jaakko, Karhunen Leila, Kas Martien J H, Keel Pamela K, Kennedy James L, Keski-Rahkonen Anna, Kiezebrink Kirsty, Klareskog Lars, Klump Kelly L, Knudsen Gun Peggy S, La Via Maria C, Le Hellard Stephanie, Leboyer Marion, Li Dong, Lilenfeld Lisa, Lin Bochao, Lissowska Jolanta, Luykx Jurjen, Magistretti Pierre, Maj Mario, Marsal Sara, Marshall Christian R, Mattingsdal Morten, Meulenbelt Ingrid, Micali Nadia, Mitchell Karen S, Monteleone Alessio Maria, Monteleone Palmiero, Myers Richard, Navratilova Marie, Ntalla Ionna, O'Toole Julie K, Ophoff Roel A, Padyukov Leonid, Pantel Jacques, Papežová Hana, Pinto Dalila, Raevuori Anu, Ramoz Nicolas, Reichborn-Kjennerud Ted, Ricca Valdo, Ripatti Samuli, Ripke Stephan, Ritschel Franziska, Roberts Marion, Rotondo Alessandro, Rujescu Dan, Rybakowski Filip, Scherag André, Scherer Stephen W, Schmidt Ulrike, Scott Laura J, Seitz Jochen, Silén Yasmina, Šlachtová Lenka, Slagboom P Eline, Slof-Op 't Landt Margarita C T, Slopien Agnieszka, Sorbi Sandro, Świątkowska Beata, Tortorella Alfonso, Tozzi Federica, Treasure Janet, Tsitsika Artemis, Tyszkiewicz-Nwafor Marta, Tziouvas Konstantinos, van Elburg Annemarie A, van Furth Eric F, Walton Esther, Widen Elisabeth, Zerwas Stephanie, Zipfel Stephan, Bergen Andrew W, Boden Joseph M, Brandt Harry, Crawford Steven, Halmi Katherine A, Horwood L John, Johnson Craig, Kaplan Allan S, Kaye Walter H, Mitchell James E, Olsen Catherine M, Pearson John F, Pedersen Nancy L, Strober Michael, Werge Thomas, Whiteman David C, Woodside D Blake, Gordon Scott, Maguire Sarah, Larsen Janne T, Parker Richard, Petersen Liselotte V, Jordan Jennifer, Kennedy Martin, Wade Tracey D, Birgegård Andreas, Lichtenstein Paul, Landén Mikael, Martin Nicholas G, Mortensen Preben Bo, Breen Gerome, Bulik Cynthia M
Аннотация
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-h 2) 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.