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Common Genetic Variation and Age of Onset of Anorexia Nervosa
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SYSNO ASEP 0576271 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Common Genetic Variation and Age of Onset of Anorexia Nervosa Author(s) Watson, H. J. (US)
Thornton, L. M. (US)
Yilmaz, Z. (US)
Baker, J. H. (US)
Coleman, J. R. I. (GB)
Adan, R. A. H. (SE)
Alfredsson, L. (SE)
Andreassen, O. A. (NO)
Ask, H. (NO)
Berrettini, W. H. (US)
Boehnke, M. (US)
Boehm, I. (DE)
Boni, C. (FR)
Buehren, K. (DE)
Bulant, J. (CZ)
Burghardt, R. (DE)
Chang, X. (US)
Cichon, S. (DE)
Cone, R. D. (US)
Courtet, P. (FR)
Crow, S. (CH)
Crowley, J. J. (SE)
Danner, U. N. (NL)
de Zwaan, M. (DE)
Dedoussis, G. (GR)
DeSocio, J. E. (US)
Dick, D. M. (US)
Dikeos, D. (GR)
Dina, C. (FR)
Šlachtová, Lenka (UOCHB-X)
Bulik, C. M. (US)Number of authors 178 Source Title Biological Psychiatry. Global Open Science. - : Elsevier - ISSN 2667-1743
Roč. 2, č. 4 (2022), s. 368-378Number of pages 11 s. Language eng - English Country US - United States Keywords genome-wide association ; eating disorders ; familial aggregation OECD category Biochemistry and molecular biology Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 001050120400008 EID SCOPUS 85129769148 DOI 10.1016/j.bpsgos.2021.09.001 Annotation 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 earlyonset 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1016/j.bpsgos.2021.09.001
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