Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

Abstract

The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P¼0.0010, odds ratio¼1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis.

Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: Evidence for a common genetic vulnerability?

“…All studies used a case-control design and clinical diagnoses of psychiatric disorders were made by interviews or examination of patients' records by psychiatrists. Seven articles described screening of the control group for psychiatric disorders (Betcheva et al, 2009;Crisan, 2006;Jonsson et al, 2008;Lee et al, 2006;Ozbek et al, 2008;Sazci et al, 2005;Vilella et al, 2005) and five articles reported matching of the control group (Crisan, 2006;Jonsson et al, 2008;Lee et al, 2006;Sazci et al, 2003Sazci et al, , 2005. All samples used a PCR-based method for genotyping the A1298C polymorphism.…”

“…These studies have yielded largely inconclusive and often mixed results (Betcheva et al, 2009;Feng et al, 2009;Gaysina et al, 2008;Gilbody et al, 2007;Pan et al, 2009;Yu et al, 2004;Yuan et al, 2008). MTHFR is a crucial enzyme involved in one-carbon metabolism (OCM), a folate-mediated pathway essential for purine and thymidylate biosynthesis, the methylation of DNA and amino acids, and is necessary for reactions forming neurotransmitters (Sugden, 2006).…”

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia

“…The lack of association of rs6675281and schizophrenia is in line with the literature. 29,43,44 The rs3738401 SNP, together with rs751229, forms a common DISC1 haplotype, HEP3, spanning 62 kb from intron 1 to exon 2. HEP3 (T-A) was found to be overtransmitted to males with schizophrenia spectrum psychosis and severe mood disorders.…”

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

“…Dysfunction of the one-carbon metabolism has been linked to a range of disorders including neural tube defects [177,178], autism [179], leukemia [180,181], dementia [182][183][184], colorectal cancer [183,185], cardiovascular disease [186] and congenital abnormalities [187,188]. Genetic studies on associations between genetic variants in Mthfr and various major psychiatric disorders such as schizophrenia, bipolar disorder and unipolar depressive disorder, have yielded largely inconclusive and often mixed results [189][190][191][192][193][194][195]. Given the essential role of Mthfr in brain function and neurodevelopment [196,197], and the fact that family and twin studies have established considerable shared genetic variance between psychiatric disorders [198][199][200], a recent meta-analysis (on a total of more than 29,000 subjects) tested whether genetic variation in Mthfr contributes to the shared genetic vulnerability of schizophrenia, bipolar disorder and unipolar depressive disorder [201].…”