Candidate genes for schizophrenia: A survey of association studies and gene ranking

Abstract

More than 500 genes have been reported with positive or negative association with schizophrenia. The wealth of this information, along with the complex nature of psychiatric disorders, provides a challenging but also unique opportunity for the investigation of molecular and cellular mechanisms in schizophrenia. In this study, we performed a comprehensive survey of the published association studies collected in the SchizophreniaGene database. We observed over time a strong trend for increases in the number of published reports, the number of studied genes, and the sample size of the studies. We also examined the studies, genes, and sample sizes in different ethnic populations and the distribution of these association studies and their employed markers among these susceptibility genes. We then selected and ranked candidate genes using a combined odds ratio method. The evaluation of this candidate gene set against sets selected by other methods suggested its utility in follow-up association studies and in further bioinformatics analysis. We also examined the functional biases of the selected genes.

Convergent functional genomics of genome‐wide association data for bipolar disorder: Comprehensive identification of candidate genes, pathways and mechanisms

“…At least part of the problem facing genetic-only approaches in complex disorders may be related to extreme genetic heterogeneity [Walsh et al, 2008]. Given the mounting convergent evidence implicating many more genes in complex disorders [Walsh et al, 2008;Sun et al, 2008a] than the small number identified by the first-generation GWAS to date, there is a strong need for improvements in methodology. One strategy is to include in the next generation of GWAS larger number of subjects, and/or pool independent studies into meta-analyses [Zeggini et al, 2008].…”

Molecular Pharmacology and Ligand Docking Studies Reveal a Single Amino Acid Difference between Mouse and Human Serotonin 5-HT2A Receptors That Impacts Behavioral Translation of Novel 4-Phenyl-2-dimethylaminotetralin Ligands

“…Serotonin (5-HT) 5-HT2A, 5-HT2B, and 5-HT2C G protein-coupled receptors (GPCRs) are pharmacotherapeutic targets of interest due in part to their involvement in several psychiatric disorders, as inferred from human genetic studies (Dracheva et al, 2008;Sun et al, 2008;Nichols, 2009;Thanseem et al, 2012). Drug discovery programs targeting 5-HT2 receptors are focused on treating psychosis (5-HT2A antagonists), sleep disorders (5-HT2A antagonists), cluster headaches (5-HT2 agonists), anxiety (5-HT2B/2C antagonists), and obesity (5-HT2C agonists) (Sewell et al, 2006;Abbas and Roth, 2008;Smith et al, 2010).…”

The Effect of Inflammation on Preterm Birth

“…However, most common variants individually or in combination confer relatively small increments in risk (1.1 to 1.5-fold) and explain only a small proportion of heritability ). According to Dolan et al (2010) genetic associations with preterm birth reveals a paucity of research in the area, compared with more mature genetic association fields like schizophrenia and Alzheimer's disease (Allen et al, 2008;Sun et al, 2008;Dolan et al, 2010). So far, no robustly replicated genetic variants contributing to this complex disease have been identified .…”