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

A. Frisch*, N. Laufer, Y. Danziger, E. Michaelovsky, S. Leor, C. Carel, D. Stein, S. Fenig, M. Mimouni, A. Apter, A. Weizman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


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% χ2 = 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 χ2 = 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.

Original languageEnglish
Pages (from-to)243-245
Number of pages3
JournalMolecular Psychiatry
Issue number2
StatePublished - 2001


FundersFunder number
German-Israeli Foundation for Scientific Research and Development
National Institute for Psychobiology in Israel, Hebrew University of Jerusalem610-212.02


    • Catechol-O-methyltransferase (COMT)
    • Eating disorders
    • Haplotype relative risk (HRR)
    • Polymorphism
    • Transmission disequilibrium test (TDT)


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