Database of genetic studies of bipolar disorder

Department of Psychiatry, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Psychiatric genetics (Impact Factor: 1.94). 11/2010; 21(2):57-68. DOI: 10.1097/YPG.0b013e328341a346
Source: PubMed


This study describes the construction and preliminary analysis of a database of summary level genetic findings for bipolar disorder from the literature. The database is available for noncommercial use at This may be the first complete collection of published gene-specific linkage and association findings on bipolar disorder, including genome-wide association studies. Both the positive and negative findings have been incorporated so that the statistical and contextual significance of each finding may be compared semi-quantitatively and qualitatively across studies of mixed technologies. The database is appropriate for searching a literature populated by mainly underpowered studies, and if 'hits' are viewed as tentative knowledge for future hypothesis generation. It can serve as the basis for a mega-analysis of candidate genes. Herein, we discuss the most robust and best replicated gene findings to date in a contextual manner.

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Available from: John E Piletz, Oct 07, 2015
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    • "Primary studies reported a potential association of anxiety-related traits and mood disorders, including BD, with the S allele of 5HTTLPR (Collier et al., 1996; Lesch et al., 1996); however, the association issue has remained controversial. Nearly half of the conducted genetic studies, including genomewide association studies and single nucleotide polymorphism (SNP) studies, have produced negative results (Piletz et al., 2011). As well, the statistically significant results of two meta-analyses on SNP studies favor the association (Cho et al., 2005; Jiang et al., 2013), whereas another meta-analysis found no significant association between 5HTTLPR and BD (Seifuddin et al., 2012). "
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    ABSTRACT: Serotonin transporter gene linked polymorphic region, also called 5HTTLPR, is a candidate in the genetics of bipolar disorder; however, the results of previous association studies are inconsistent. Several explanations have been proposed for that inconsistency; among them are the existing differences both in the genetic basis of bipolar disorder subtypes and the genetic backgrounds of the studied populations. We aimed to investigate the association of 5HTTLPR with bipolar disorder type I (BP-1) in Iranian population. In this case-control study, 146 patients with BP-1 and 165 controls were recruited. The patients were selected through the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition. It was required that the patients do not have any present history of general medical conditions, substance abuse, and concurrent major psychiatric disorders. The polymorphism was evaluated by blood sampling and subsequent DNA extraction, polymerase chain reaction, and agarose gel electrophoresis. Chi-square test was used for analyzing allelic and genotype frequencies and two-tailed P values were obtained. The S allele was significantly more frequent in the BP-1 patients compared with the controls (P = 0.02, S allele odds ratio = 1.5, confidence interval 95% = 1.06-2.11). Our statistically significant results suggest that the role of 5HTTLPR in the pathogenesis of BP-1 needs to be clarified by further scrutiny in Iranian population and other populations of Near East. © 2015 Wiley Publishing Asia Pty Ltd.
    Asia-Pacific Psychiatry 03/2015; DOI:10.1111/appy.12179 · 0.63 Impact Factor
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    • "The genes and environmental factors implicated in the various diseases (Alzheimer's disease, attention deficit hyperactivity disorder, autism, bipolar disorder, chronic fatigue syndrome, depression, schizophrenia, multiple sclerosis , Parkinson's disease, anorexia, and childhood obesity ) are listed at PolygenicPathways (http://www.polygenicpathways and at sites therein (including the autism database at Mindspec (AutDB) [40], the Bipolar database at the University of Chicago [41], AlzGene, MSGene, PDGene and SZGene [42] [43] [44] [45]). Genome-wide association data can be accessed at the National Human Genome Research Institute "
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    ABSTRACT: Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P from 8.01E - 05 (ADHD) to 1.22E - 71) (multiple sclerosis), and autism (P = 0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself.
    03/2013; 2013(2):965046. DOI:10.1155/2013/965046
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    • "Specific glutamatergic neurotransmission candidate susceptibility genes include citron (CIT) positive (Lyons-Warren et al., 2005) and negative (Yosifova et al., 2009), D-amino acid oxidase (DAO) positive (Fallin et al., 2005; Prata et al., 2008) and negative (Shi et al., 2008), and the nitric oxide synthase (NOS) genes NOS1 (neuronal) positive (Fallin et al., 2005; Yosifova et al., 2009) and negative (Buttenschon et al., 2004; Gratacos et al., 2009; Okumura et al., 2010), and NOS3 (endothelial) positive (Reif et al., 2006) and negative (Gratacos et al., 2009; Sklar et al., 2002). GluRs identified as BP candidate genes include the ionotropic α-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor subunits GRIA1 positive (Kerner et al., 2009; Shi et al., 2008) and negative (Gratacos et al., 2009), GRIA2 positive (Perlis et al., 2009) and negative (Shi et al., 2008; Sklar et al., 2002), kainate (KA) receptor subunit GRIK4 positive (Pickard et al., 2008; Pickard et al., 2006) and negative (Gratacos et al., 2009), N-methyl-D-aspartate (NMDA) receptor subunits GRIN1 positive (Mundo et al., 2003; Shi et al., 2008; Yosifova et al., 2009) and negative (Georgi et al., 2006), GRIN2A positive (Itokawa et al., 2003) and negative (Gratacos et al., 2009; Shi et al., 2008), GRIN2B positive (Avramopoulos et al., 2007; Fallin et al., 2005; Lorenzi et al., 2010; Martucci et al., 2006; Zhao et al., 2011) and negative (Gratacos et al., 2009; Shi et al., 2008), GRIN2C positive (Shi et al., 2008), and GRIN2D positive (Shi et al., 2008), and metabotropic glutamate receptors (mGluRs) GRM1 positive (Baum et al., 2008; Frank et al., 2011) and negative (Fan et al., 2010; Shi et al., 2008), GRM3 positive (Fallin et al., 2005; Sklar et al., 2008) and negative (Gratacos et al., 2009; Marti et al., 2002; Shi et al., 2008; Yosifova et al., 2009), GRM4 positive (Fallin et al., 2005) and negative (Shi et al., 2008; Sklar et al., 2002), GRM7 positive (Gratacos et al., 2009) and negative (Baum et al., 2008; Shi et al., 2008; Sklar et al., 2002; Yosifova et al., 2009), among other glutamatergic neurotransmission candidates (Cherlyn et al., 2010; Piletz et al., 2011). A high percentage of these glutamatergic neurotransmission/GluR candidate genes also overlap in susceptibility with SZ (Cherlyn et al., 2010; Fallin et al., 2005; Frank et al., 2011; Marti et al., 2002; Martucci et al., 2006; Pickard et al., 2006), highlighting the complex, multigenic, multifactorial nature of these neuropsychiatric disorders and the difficulty teasing apart genes that might discriminate these two conditions. "
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    ABSTRACT: Functional genomics and proteomics approaches are being employed to evaluate gene and encoded protein expression changes with the tacit goal to find novel targets for drug discovery. Genome-wide association studies (GWAS) have attempted to identify valid candidate genes through single nucleotide polymorphism (SNP) analysis. Furthermore, microarray analysis of gene expression in brain regions and discrete cell populations has enabled the simultaneous quantitative assessment of relevant genes. The ability to associate gene expression changes with neuropsychiatric disorders, including bipolar disorder (BP), and their response to therapeutic drugs provides a novel means for pharmacotherapeutic interventions. This review summarizes gene and pathway targets that have been identified in GWAS studies and expression profiling of human postmortem brain in BP, with an emphasis on glutamate receptors (GluRs). Although functional genomic assessment of BP is in its infancy, results to date point towards a dysregulation of GluRs that bear some similarity to schizophrenia (SZ), although the pattern is complex, and likely to be more complementary than overlapping. The importance of single population expression profiling of specific neurons and intrinsic circuits is emphasized, as this approach provides informative gene expression profile data that may be underappreciated in regional studies with admixed neuronal and non-neuronal cell types.
    Pharmacology Biochemistry and Behavior 02/2012; 100(4):705-11. DOI:10.1016/j.pbb.2011.09.015 · 2.78 Impact Factor
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