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

TY - JOUR

T1 - Risk factors for anorexia nervosa

T2 - A population-based investigation of sex differences in polygenic risk and early life exposures

AU - Chatwin, Hannah

AU - Holde, Katrine

AU - Yilmaz, Zeynep

AU - Larsen, Janne Tidselbak

AU - Albiñana, Clara

AU - Vilhjálmsson, Bjarni Jóhann

AU - Mortensen, Preben Bo

AU - Thornton, Laura M

AU - Bulik, Cynthia M

AU - Petersen, Liselotte Vogdrup

N1 - © 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - anorexia nervosa

KW - epidemiology

KW - polygenic risk

KW - risk factors

KW - sex differences

U2 - 10.1002/eat.23997

DO - 10.1002/eat.23997

M3 - Journal article

C2 - 37232007

SN - 0276-3478

VL - 56

SP - 1703

EP - 1716

JO - International Journal of Eating Disorders

JF - International Journal of Eating Disorders

IS - 9

ER -