After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder

Gershon, Elliot S.; Alliey‐Rodriguez, Ney; Liu, Chun Yu

doi:10.1176/appi.ajp.2010.10091340

Cited by 179 publications

(127 citation statements)

References 19 publications

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“…Most recent evidence supports a combination of genetic and environmental factors contributing to the development of the disorder (Marenco and Weinberger, 2000). To date, no one gene, single-nucleotide polymorphism, or mutation has been consistently linked to the illness, and it is likely that multiple susceptibility genes create a predisposition to developing schizophrenia (Fanous et al, 2012;Gershon et al, 2011;Levinson et al, 2012). Genetics studies, which have led the way for diseases such as breast cancer and cystic fibrosis, have been much less impactful in the schizophrenia field.…”

Section: Introduction: the Problem Of Schizophreniamentioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

107

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We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness.

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Section: Introduction: the Problem Of Schizophreniamentioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

107

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“…Is now plausible that multiple rare variants each have a potent effect on disease risk and that they could accumulate to become a substantial component of mental disease risk 44 . The search for genetic information that are associated with the outbreak of TB involves structural and environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Associação entre polimorfismos genéticos e transtorno bipolar

Alves¹,

Silva²,

Neto³

et al. 2012

Rev. psiquiatr. clín.

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Bipolar disorder (BD) is a common disorder that affects approximately 1% of the population. It is associated with both chronic and acute severe features, such as low remission rates and a high prevalence of clinical and psychiatric comorbidities. The aim of the present article is to synthesize data from various articles that investigated genetic polymorphisms associated with BD. The 129 articles selected identified 79 (85.87%) genes associated with BD. This analysis identified the five genes that are the most cited in the literature: CANAC1C, DAOA, TPH2, ANK3 and DISC1. Of the 92 genes identified in these articles, 33 (35.87%) showed no association with BD. This analysis showed that, despite recent advances with respect to the role of genetic polymorphism in predisposition to BD, further research is still required to elucidate its influence on this disorder.Alves VM, et al. / Rev Psiq Clín. 2012;39(1):34-9 Keywords: Bipolar disorder, genes, polymorphisms, heredity, gene ontology, association with bipolar disorder. ResumoTranstorno bipolar (TB) é uma doença comum que afeta aproximadamente 1% da população. Apresenta características crônicas e agudas graves, com índices de remissão de baixa e alta prevalência de comorbidades clínicas e psiquiátricas. O objetivo do presente artigo é sintetizar dados de vários artigos que investigaram polimorfismos genéticos associados com TB. Dentre os 129 artigos selecionados, identificaram-se 79 (85,87%) genes associados com TB. Essa análise identificou cinco genes que são os mais citados na literatura: CANAC1C, DAOA, TPH2, ANK3 e DISC1. Dos 92 genes identificados nesses artigos, 33 (35,87%) não mostraram associação com TB. Essa análise mostrou que, apesar dos avanços recentes com relação ao papel do polimorfismo genético na predisposição para TB, mais pesquisas ainda são necessárias para elucidar sua influência sobre esse transtorno.Alves VM, et al. / Rev Psiq Clín. 2012;39(1):34-9 Palavras-chave: Transtorno bipolar, genes, polimorfismos, hereditariedade, ontologia genética, associação com transtorno bipolar.

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“…In the long term the aim will be to undertake studies similar to GWAS with very large sample sizes [113]. Until sequencing technology is inexpensive enough to perform these large sample studies various approaches have been suggested to further our understanding.…”

Section: Next Generation Sequencingmentioning

confidence: 99%

Genetics of Schizophrenia and other Psychotic Disorders

Pepper¹,

Cardno²

2014

CPSR

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Abstract:Research into the genetic basis of schizophrenia is advancing rapidly. This review gives a broad overview of results from successive phases of studies in this field, linking these with recent findings and likely future research directions. Among recent findings, large-scale epidemiological studies based on Scandinavian population registers, have provided further evidence of substantial heritability and evidence that a wide range of psychotic and non-psychotic disorders partly share genetic risk factors with schizophrenia. In molecular genetics, large collaborative genomewide association studies (GWAS) are providing evidence of common risk variants, each of small effect, and many more variants are likely to be found as samples sizes increase further. A range of rarer chromosomal copy number variants (CNVs) have been associated with schizophrenia, and both GWAS and CNV studies have provided molecular evidence of genetic overlap between schizophrenia and other disorders. There is increasing interest in phenotypes beyond diagnosis, including further clinical variables and endophenotypes. Next-generation sequencing studies are beginning, with the potential for fast, inexpensive sequencing of the whole genome in large samples, and there is an increasing focus on the functional effects of the candidate risk variants that are being identified.

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After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder

Cited by 179 publications

References 19 publications

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

Associação entre polimorfismos genéticos e transtorno bipolar

Genetics of Schizophrenia and other Psychotic Disorders

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