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-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.

© 2021 The Authors.

Overview publication

TitleCommon Genetic Variation and Age of Onset of Anorexia Nervosa.
DateOctober 1st, 2022
Issue nameBiological psychiatry global open science
Issue numberv2.4:368-378
DOI10.1016/j.bpsgos.2021.09.001
PubMed36324647
AuthorsWatson HJ, Thornton LM, Yilmaz Z, Baker JH, Coleman JRI, Adan RAH, Alfredsson L, Andreassen OA, Ask H, Berrettini WH, Boehnke M, Boehm I, Boni C, Buehren K, Bulant J, Burghardt R, Chang X, Cichon S, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, de Zwaan M, Dedoussis G, DeSocio JE, Dick DM, Dikeos D, Dina C, Djurovic S, Dmitrzak-Weglarz M, Docampo-Martinez E, Duriez P, Egberts K, Ehrlich S, Eriksson JG, Escaramís G, Esko T, Estivill X, Farmer A, Fernández-Aranda F, Fichter MM, Föcker M, Foretova L, Forstner AJ, 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 SG, Herms S, Herpertz-Dahlmann B, Herzog W, Hinney A, Hübel C, Hudson JI, Imgart H, Jamain S, Janout V, Jiménez-Murcia S, Jones IR, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Kas MJH, Keel PK, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Leboyer M, Li D, Lilenfeld L, Lin B, Lissowska J, Luykx J, Magistretti P, Maj M, Marsal S, Marshall CR, Mattingsdal M, Meulenbelt I, Micali N, Mitchell KS, Monteleone AM, Monteleone P, Myers R, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, 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 SW, Schmidt U, Scott LJ, Seitz J, Silén Y, Šlachtová L, Slagboom PE, Slof-Op 't Landt MCT, Slopien A, Sorbi S, Świątkowska B, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Walton E, Widen E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Gordon S, Maguire S, Larsen JT, Parker R, Petersen LV, Jordan J, Kennedy M, Wade TD, Birgegård A, Lichtenstein P, Landén M, Martin NG, Mortensen PB, Breen G & Bulik CM
KeywordsAge of onset, Anorexia nervosa, Early-onset, GWAS, Genetic risk score, Genetics, Menarche, Mendelian randomization, Puberty
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