Department of Economics and Business Economics

Polygenic association with severity and long-term outcome in eating disorder cases

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  • Therese Johansson, Karolinska Institutet, Uppsala University
  • ,
  • Andreas Birgegård, Karolinska Institutet
  • ,
  • Ruyue Zhang, Karolinska Institutet
  • ,
  • Sarah E Bergen, Karolinska Institutet
  • ,
  • Mikael Landén, Karolinska Institutet, University of Gothenburg
  • ,
  • Liselotte V Petersen
  • Cynthia M Bulik, Karolinska Institutet, University of North Carolina
  • ,
  • Christopher Hübel

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 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the 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 (β PGS  = 1.30; 95% CI: 0.72, 1.88; p = 1.2 × 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.

Original languageEnglish
Article number61
JournalTranslational Psychiatry
Volume12
Issue1
Number of pages12
ISSN2158-3188
DOIs
Publication statusPublished - 2022

    Research areas

  • ENDURING ANOREXIA-NERVOSA, FOLLOW-UP, GENETIC CORRELATIONS, GENOME-WIDE ASSOCIATION, INPATIENT, MASS INDEX, PERCENT BODY-FAT, RECOVERY, RISK-FACTOR, SCHIZOPHRENIA

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