Bipolar disorder (BD) is a complex disease with a high hereditability (around 80%) [1]. Despite a large amount of studies investigated genetic underpinnings of BD, to date they are still largely unknown. This is mostly due to the fact that several genes contribute to the liability to develop the disorder, each with a small effect size, furthermore pertaining to several different molecular pathways [2]. A further complication for the study of the genetics of BD is related to the influence of environmental factors that may explain a significant proportion of the risk to develop BD [3]. Nonetheless, some consistent findings have been obtained for several genes and new promising genes are receiving growing interest. In the present chapter, we aim to summarize current knowledge on genes consistently associated to BD, as well as to review new potential candidate genes. In brief, among several genes investigated in literature, the most replicated results [2] were found for some serotonin-related genes, especially SLC6A4 and TPH2 which have been consistently associated to the disease. Dopaminergic genes also, such as DRD4 and SLC6A3, are well-established genes. Other promising genes are related to amines metabolism: in particular the MAOA has been widely investigated in BD because of its key function in the degradation of serotonin, norepinephrine and dopamine. Furthermore, circadian rhythms related genes have been associated with the disease, such as PER3, ARNTL, and CLOCK. Even if this group of genes needs to be more extensively investigated, they are of particular interest because several lines of evidence point to circadian dysfunction in BD pathogenesis [4]. In the last few years, genome-wide association studies (GWAS) allowed to identify many new interesting susceptibility loci. Nevertheless, results are not replicated or only partially replicated in most of the cases. In addition increasing evidence suggests an overlap in genetic susceptibility with schizophrenia and some genes have been associated with both disorders [5].

Genetic basis of Bipolar disorder

MANDELLI, LAURA;Fabbri C.;SERRETTI, ALESSANDRO
2011

Abstract

Bipolar disorder (BD) is a complex disease with a high hereditability (around 80%) [1]. Despite a large amount of studies investigated genetic underpinnings of BD, to date they are still largely unknown. This is mostly due to the fact that several genes contribute to the liability to develop the disorder, each with a small effect size, furthermore pertaining to several different molecular pathways [2]. A further complication for the study of the genetics of BD is related to the influence of environmental factors that may explain a significant proportion of the risk to develop BD [3]. Nonetheless, some consistent findings have been obtained for several genes and new promising genes are receiving growing interest. In the present chapter, we aim to summarize current knowledge on genes consistently associated to BD, as well as to review new potential candidate genes. In brief, among several genes investigated in literature, the most replicated results [2] were found for some serotonin-related genes, especially SLC6A4 and TPH2 which have been consistently associated to the disease. Dopaminergic genes also, such as DRD4 and SLC6A3, are well-established genes. Other promising genes are related to amines metabolism: in particular the MAOA has been widely investigated in BD because of its key function in the degradation of serotonin, norepinephrine and dopamine. Furthermore, circadian rhythms related genes have been associated with the disease, such as PER3, ARNTL, and CLOCK. Even if this group of genes needs to be more extensively investigated, they are of particular interest because several lines of evidence point to circadian dysfunction in BD pathogenesis [4]. In the last few years, genome-wide association studies (GWAS) allowed to identify many new interesting susceptibility loci. Nevertheless, results are not replicated or only partially replicated in most of the cases. In addition increasing evidence suggests an overlap in genetic susceptibility with schizophrenia and some genes have been associated with both disorders [5].
Bipolar Disorder: Causes, Diagnosis and Treatment
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Mandelli L.; Porcelli S.; Fabbri C.; Serretti A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/103619
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