Year: 2022
Type: article
Study design: Observational Study
Abstract: About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksät and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2,843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 yrs). Second, we indexed development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time ≥5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping and p value thresholding was robustly associated with disorder severity (βPGS = 1.30; 95% CI: 0.72, 1.88; p = 1.2 x 10-5) across all p value thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders.
Source: Translational Psychiatry
Institutions: Uppsala University, Science for Life Laboratory, Karolinska Institutet, University of Gothenburg, Aarhus University, University of North Carolina at Chapel Hill, King's College London, South London and Maudsley NHS Foundation Trust, National Institute for Health and Care Research, Maudsley Hospital
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $4,590
Funders: U.S. Department of Health and Human Services, Klarman Family Foundation, South London and Maudsley NHS Foundation Trust, Maudsley Charity, National Institute for Health and Care Research, King's College London, Lundbeckfonden, Vetenskapsrådet, H. Lundbeck A/S, National Institute of Mental Health
Awards: G103800658, G1181994271, G1375331873, Eating Disorders Genetics Initiative (EDGI), G2082591074, G211885902, G2332261527, G2417586468, G2953470886, G303339423, G3197369316, G3298186876, G3747547992, G3964009410, G4034426326, Predicting Binge and Purge Episodes from Passive and Active Apple Watch Data Using a Dynamical Systems Approach, A MULTI-PRONGED STRATEGY FOR THE STUDY OF BIPOLAR DISORDER, G4670273794, G5012122282, G5197328387, G5408826359, G5789614150, G7080914213, G712881263, G72353583, Predicting the multi-omic impact of psychiatric GWAS associations, G8652487745, 1/7 PGC: Advancing Discovery and Impact
OpenAlex ID: W4220905122