Abstract
Dr. Sand et al in press Sand P, Eichhammer P, Langguth B, Hajak G (in press): COMT association data in schizophrenia: new caveats. Biol Psychiatry. Google Scholar have pointed out the limitation of using “haplotype relative risk” model to calculate the effect size of transmission/disequilibrium test (TDT) studies in a previous study ( Glatt et al 2003 Glatt S.J. Faraone S.V. Tsuang M.T. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: Meta-analysis of case-control and family-based studies. Am J Psychiatry. 2003; 160: 469-476 Crossref PubMed Scopus (311) Google Scholar ). They further used the method introduced by Lohmueller et al 2003 Lohmueller K.E. Pearce C.L. Pike M. Lander E.S. Hirschhorn J.N. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003; 33: 177-182 Crossref PubMed Scopus (1615) Google Scholar to re-analyze the five TDT studies in that study and found no significant overall evidence for association between the catechol-O-methyltransferase (COMT) Val allele and schizophrenia in both European and Asian populations. They therefore concluded that the combined results from the TDT studies are now in better agreement with our previous observations ( Fan et al 2005 Fan J.B. Zhang C.S. Gu N.F. Li X.W. Sun W.W. Wang H.Y. et al. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: A large-scale association study plus meta-analysis. Biol Psychiatry. 2005; 57: 139-144 Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar ). COMT Association Data in Schizophrenia: New CaveatsBiological PsychiatryVol. 60Issue 6PreviewFan et al (2005) have alerted us to the unresolved disparity between ethnicities regarding catechol-O-methyltransferase (COMT) effect size in family-based association studies of schizophrenia. According to Glatt et al (2003), it would seem that only in Europeans is the effect of the Val allele considerably stronger (odds ratio [OR] = 2.2) than is observed in population-based association studies (OR = 1.1). There is reason to doubt this view, because Glatt et al (2003) re-calculated ORs for the original studies with a model known as the “haplotype relative risk” model. Full-Text PDF
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