1. ¹Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA
2. ²The Department of Psychiatry, The Queens University, Belfast, Northern Ireland
3. ³The Health Research Board, Dublin, Ireland

Correspondence: X Chen, PhD, Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, VA 23298, USA. Email: xchen@vcu.edu; Tel: 804 828 8124; Fax: 804 828 1471

Received 16 December 2003; Revised 17 March 2004; Accepted 17 March 2004; Published online 4 May 2004.

Abstract

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.