PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Lu, Z.A.* ; Ploner, A.* ; Birgegård, A.* ; Eating Disorders Working Group of the Psychiatric Genomics Consortium (Zeggini, E. ; Wichmann, H.-E. ; Southam, L. ; Hatzikotoulas, K.) ; Landén, M.* ; Bulik, C.M.* ; Bergen, S.E.*

Leveraging transdiagnostic genetic liability to psychiatric disorders to dissect clinical outcomes of anorexia nervosa.

Mol. Psychiatry, DOI: 10.1038/s41380-025-03264-x (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Anorexia nervosa (AN) has extensive genetic correlations with other psychiatric disorders, and genetic risk for different psychiatric disorders was associated with distinct clinical courses in AN. Uncovering associations between transdiagnostic psychiatric genetic liability and AN outcomes can facilitate its personalized treatment. In this study, we investigated the associations between transdiagnostic psychiatric genetic liability and outcomes of AN. Genomic structural equation models were fitted to genome-wide association data for AN and psychiatric disorders with high genetic correlations with AN (obsessive-compulsive symptoms [OCS], major depressive disorder [MDD], schizophrenia, and anxiety disorders) to extract one shared and five trait-specific genetic components. Next, we calculated the polygenic risk scores (PRS) for these components, including PRSshared, PRSAN-specific, PRSOCS-specific, PRSMDD-specific, PRSSCZ-specific and PRSANX-specific, which index the shared genetic liability to all five psychiatric traits, and genetic liability specific to AN, OCS, MDD, SCZ and ANX, respectively. We then tested associations between these PRSs and clinical outcomes reported between 1997 and 2018 among AN cases from the Anorexia Nervosa Genetics Initiative (ANGI), linked to Swedish National Registers. The clinical outcomes included cumulative disease burden (i.e., number of diagnoses, medication prescriptions, and inpatient days), risks of psychiatric comorbidities, and AN symptomatology. Among 4028 included AN cases, the mean (SD) birth year was 1985 (9), and 3947 (98.0%) were female. Within AN, +1 SD increase of PRSshared was associated with 9–39% excess risk of disease burden and psychiatric comorbidity, whereas the associations between PRSAN-specific and most clinical outcomes were statistically non-significant. +1 SD increase of PRSMDD-specific was associated with 3–29% increased risk of AN disease burden. Our findings show that shared psychiatric liability is associated with more adverse AN outcomes, whereas AN-specific liability is not a good indicator for its clinical course. This study provides a novel perspective on factors influencing heterogeneity in AN clinical course.
Impact Factor
Scopus SNIP
Altmetric
10.100
2.523
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506700-001
G-504000-009
DOI 10.1038/s41380-025-03264-x
Scopus ID 105018071077
PubMed ID 40983652
Erfassungsdatum 2025-10-16
[➜Report correction]