Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients

Mol Psychiatry. 2001 Mar;6(2):243-5. doi: 10.1038/


Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance. Family and twin studies indicate a significant genetic contribution and pharmacological data suggest possible dysfunction of the serotonergic and dopaminergic pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles. Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% chi(2) = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemar's chi(2) = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Anorexia Nervosa / epidemiology
  • Anorexia Nervosa / genetics*
  • Catechol O-Methyltransferase / genetics*
  • Family Health*
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Israel
  • Linkage Disequilibrium
  • Polymorphism, Genetic*
  • Risk Factors


  • Catechol O-Methyltransferase