Common Genetic Variation and Age of Onset of Anorexia Nervosa
Publication date
2022-10
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.
Editors
Advisors
Supervisors
Document Type
Article
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Abstract
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.
Keywords
Age of onset, Anorexia nervosa, Early-onset, Genetic risk score, Genetics, GWAS, Menarche, Mendelian randomization, Puberty, Phychiatric Mental Health, Clinical Neurology, Psychiatry and Mental health, Biological Psychiatry, SDG 3 - Good Health and Well-being
Citation
Watson, H J, Thornton, L M, Yilmaz, Z, Baker, J H, Coleman, J R I, Adan, R A H, Alfredsson, L, Andreassen, O A, Ask, H, Berrettini, W H, Boehnke, M, Boehm, I, Boni, C, Buehren, K, Bulant, J, Burghardt, R, Chang, X, Cichon, S, Cone, R D, Courtet, P, Crow, S, Crowley, J J, Danner, U N, de Zwaan, M, Dedoussis, G, DeSocio, J E, Dick, D M, Dikeos, D, Dina, C, Djurovic, S, Dmitrzak-Weglarz, M, Docampo-Martinez, E, Duriez, P, Egberts, K, Ehrlich, S, Eriksson, J G, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Fernández-Aranda, F, Fichter, M M, Föcker, M, Foretova, L, Forstner, A J, Frei, O, Gallinger, S, Giegling, I, Giuranna, J, Gonidakis, F, Gorwood, P, Gratacòs, M, Guillaume, S, Guo, Y, Hakonarson, H, Hauser, J, Havdahl, A, Hebebrand, J, Helder, S G, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Hinney, A, Hübel, C, Hudson, J I, Imgart, H, Jamain, S, Janout, V, Jiménez-Murcia, S, Jones, I R, Julià, A, Kalsi, G, Kaminská, D, Kaprio, J, Karhunen, L, Kas, M J H, Keel, P K, Kennedy, J L, Keski-Rahkonen, A, Kiezebrink, K, Klareskog, L, Klump, K L, Knudsen, G P S, La Via, M C, Le Hellard, S, Leboyer, M, Li, D, Lilenfeld, L, Lin, B, Lissowska, J, Luykx, J, Magistretti, P, Maj, M, Marsal, S, Marshall, C R, Mattingsdal, M, Meulenbelt, I, Micali, N, Mitchell, K S, Monteleone, A M, Monteleone, P, Myers, R, Navratilova, M, Ntalla, I, O'Toole, J K, Ophoff, R A, Padyukov, L, Pantel, J, Papežová, H, Pinto, D, Raevuori, A, Ramoz, N, Reichborn-Kjennerud, T, Ricca, V, Ripatti, S, Ripke, S, Ritschel, F, Roberts, M, Rotondo, A, Rujescu, D, Rybakowski, F, Scherag, A, Scherer, S W, Schmidt, U, Scott, L J, Seitz, J, Silén, Y, Šlachtová, L, Slagboom, P E, Slof-Op ‘t Landt, M C T, Slopien, A, Sorbi, S, Świątkowska, B, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, A A, van Furth, E F, Walton, E, Widen, E, Zerwas, S, Zipfel, S, Bergen, A W, Boden, J M, Brandt, H, Crawford, S, Halmi, K A, Horwood, L J, Johnson, C, Kaplan, A S, Kaye, W H, Mitchell, J E, Olsen, C M, Pearson, J F, Pedersen, N L, Strober, M, Werge, T, Whiteman, D C, Woodside, D B, Gordon, S, Maguire, S, Larsen, J T, Parker, R, Petersen, L V, Jordan, J, Kennedy, M, Wade, T D, Birgegård, A, Lichtenstein, P, Landén, M, Martin, N G, Mortensen, P B, Breen, G & Bulik, C M 2022, 'Common Genetic Variation and Age of Onset of Anorexia Nervosa', Biological Psychiatry Global Open Science, vol. 2, no. 4, pp. 368-378. https://doi.org/10.1016/j.bpsgos.2021.09.001