The Role of a Catechol-O-Methyltransferase (COMT) Val158Met Genetic Polymorphism in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816 Subjects

Abstract

An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case-control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion. The genotype distribution of subjects with schizophrenia was compared with healthy control subjects, using allelic, additive, dominant and recessive models. The pooled results from the meta-analysis (15,565 cases and 17,251 healthy subjects) after the elimination of heterogeneity showed an association between COMT Val108/158Met and schizophrenia [recessive model: OR 1.08 CI 95 % (1.01-1.15)]. We conducted subgroup analyses according to ethnicity. An association was observed in our Caucasian population in the additive model [OR 1.21 CI 95 % (1.06-1.37)] and in the recessive model [OR 1.21 CI 95 % (1.11-1.32)], but not in the allelic or dominant models. However, when we analysed our Asian population after the elimination of heterogeneity, no evidence of a significant association was found in any of the genetic models. Our analyses indicate that there is an association between COMT Val108/158Met and schizophrenia in the general population. Furthermore, in Caucasian populations, this risk could be increased.

Collaborative Counseling Considerations for Pharmacogenomic Tests

“…For example, recent reports indicate that the rs4680 (Val158Met) variant in the COMT gene that is on PGx test panels for psychiatric drugs 27 has a statistically significant relationship with schizophrenia. 45 However, the range of odds ratios quantifying the magnitude of this association where the relationship was greatest was 1.11-1.32 in whites. Although this is an 11-32% increase statistically, in the context of a disease where the baseline risk in the population is~1%, carrying the associated variant translates into a 1.1-1.3% risk of developing the disease.…”

“…Many of the disease phenotypes identified in association studies are known to be highly polygenic, and the associations may increase the overall risk for developing a particular condition very marginally. For example, recent reports indicate that the rs4680 (Val158Met) variant in the COMT gene that is on PGx test panels for psychiatric drugs has a statistically significant relationship with schizophrenia . However, the range of odds ratios quantifying the magnitude of this association where the relationship was greatest was 1.11–1.32 in whites.…”

Opportunities for an enhanced integration of neuroscience and genomics

“…For example, some studies examined the COMT Val158Met SNP (rs4680), involved in pre-frontal dopamine levels (e.g., Cerasa et al 2008; Egan et al 2001; Honea et al 2009; Taylor et al 2007), and the serotonin-transporter-linked polymorphic region (5-HTTLPR) in the serotonin transporter gene (SLC6A4; e.g., Dutt et al 2009; Hariri et al 2002). However the replication rate of these associations was often ill-fated (e.g., Barnes et al 2009; Gonzalez-Castro et al 2016; Nickl-Jockschat et al 2015; Wang et al 2013). This trend of unsuccessful candidate gene replications is not limited to imaging genetics studies, and problems with candidate gene studies have been well documented in many areas of psychiatric genetics (e.g., Duncan and Keller 2011; Karg et al 2011).…”

The Relationship between Mismatch Negativity and the <b><i>COMT</i></b>Val108/158Met Genotype in Schizophrenia

“…COMT shows a close relationship with DA. The COMT gene is thought to be related to the etiology of schizophrenia [9] and has thus attracted attention. The COMT gene is located on chromosome 22q11, a region involved in schizophrenia [10].…”