Risk factors for anorexia nervosa: A population-based investigation of sex differences in polygenic risk and early life exposures

Hannah Chatwin*, Katrine Holde, Zeynep Yilmaz, Janne Tidselbak Larsen, Clara Albiñana, Bjarni Jóhann Vilhjálmsson, Preben Bo Mortensen, Laura M Thornton, Cynthia M Bulik, Liselotte Vogdrup Petersen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

2 Citations (Scopus)
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Abstract

OBJECTIVE: To examine sex differences in risk factors for anorexia nervosa (AN).

METHOD: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome.

RESULTS: The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons.

CONCLUSIONS: Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures.

PUBLIC SIGNIFICANCE: Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.

Original languageEnglish
JournalInternational Journal of Eating Disorders
Volume56
Issue9
Pages (from-to)1703-1716
Number of pages14
ISSN0276-3478
DOIs
Publication statusPublished - Sept 2023

Keywords

  • anorexia nervosa
  • epidemiology
  • polygenic risk
  • risk factors
  • sex differences

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