Year: 2026
Type: article
Abstract: ABSTRACT Objective Individuals with anorexia nervosa (AN) share premorbid traits with Parkinson's Disease (PD) (e.g., anxiety) and exhibit a two‐fold relative risk of a reported family history of PD. Published estimates of intra‐ and inter‐disorder genetic architecture were extracted and compared prior to conducting novel analyses to provide evidence for cross‐disorder genetic risk. Methods National register or meta‐analytic familial, twin, and common variant genome‐wide studies were searched; estimates and findings were extracted and compared. Novel cross‐disorder conditional and conjunctional false discovery rate analyses were performed. Results Sibling relative risks and additive genetic estimates of the two disorders were similar. AN had greater common variant heritability than PD whether measured via infinitesimal model (linkage disequilibrium score regression, LDSC) or causal mixture model (MiXeR). AN had greater polygenicity than PD (mean (SD) 2.50E‐03 (1.64E‐04) versus 2.72E‐4 (1.47E‐05), p < 0.001), but lower discoverability than PD (4.20E‐05 (2.69E‐06) versus 1.40E‐04 (6.95E‐06), p < 0.001). Global genetic correlation was significant (e.g., bivariate LDSC r g = 0.10, p = 0.0033). Novel analyses identified cross‐disorder enrichment, and cross‐disorder risk at chr3p21.31. Conclusions Cross‐disorder AN and PD research identified shared risk variants at chr3p21.31, genes and mechanisms (e.g., conditioning, fear, and reward) linked to a shared endophenotype.
Source: European Eating Disorders Review
DOI: 10.1002/erv.70158
Authors: Andrew W. Bergen, Carolina Makowski, Michael Garvin, Gulcan Cil, Angeline Krueger, Karlee McGlone, Irene Litvan, Heather Hower, Walter H. Kaye
Institutions: Oregon Research Institute, University of California San Diego
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: bronze
Funders: Brain and Behavior Research Foundation, Children's Hospital of Philadelphia, Louis and Harold Price Foundation, Wellcome Trust, Parkinson's Foundation, Genentech, University of California, San Diego, National Institute on Aging, National Institute of Mental Health, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke
Awards: Assessing skin biomarkers for preclinical diagnosis of PD and non-PD Parkinsonism, G7562614201, ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration, Cycle 2 (ALLFTD2), UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, The Progressive Supranuclear Palsy Clinical Trial Platform (PTP), Towards an etiological model of adolescent eating disorders through neuroimaging, genetics, and behavior, Dementia with Lewy Bodies Consortium
OpenAlex ID: W7212132007
