Genetic Variants Involved in Bipolar Disorder, a Rough Road Ahead

Germano Orrù1, 2, *, Mauro Giovanni Carta3
1 Department of Surgical Sciences, Molecular Biology Service (MBS), University of Cagliari, Cagliari, Italy
2 National Research Council of Italy, ISPA, Sassari, Italy
3 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

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Creative Commons License
© 2018 Orrù and Carta.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Surgical Sciences, University of Cagliari, Germano Orrù Ph.D, via Ospedale 54, 09124 Cagliari, Italy; Tel: +39 070 609-2568; E-mail: orru@unica.it



Bipolar Disorder (BD), along with depression and schizophrenia, is one of the most serious mental illnesses, and one of the top 20 causes of severe impairment in everyday life. Recent molecular studies, using both traditional approaches and new procedures such as Whole-Genome Sequencing (WGS), have suggested that genetic factors could significantly contribute to the development of BD, with heritability estimates of up to 85%. However, it is assumed that BD is a multigenic and multifactorial illness with environmental factors that strongly contribute to disease development/progression, which means that progress in genetic knowledge of BD might be difficult to interpret in clinical practice.


The aim of this study is to provide a synthetic description of the main SNPs variants identified/confirmed by recent extensive WGS analysis as well as by reconstruction in an in vitro mechanism or by amygdala activation protocol in vivo.


Bibliographic data, genomic and protein Data Banks were consulted so as to carry out a cross genomic study for mutations, SNPs and chromosomal alterations described in these studies in BD patients.


Fifty-five different mutations have been described in 30 research papers by different genetic analyses including recent WGS analysis. Many of these studies have led to the discovery of the most probable susceptibility genes for BD, including ANK3, CACNA1C, NCAN, ODZ4, SYNE1, and TRANK1. Exploration has started the role of several of these mutations in BD pathophysiology using in vitro and animal models.


Although new genomic research technology in BD opens up new possibilities, the current results for common variants are still controversial because of four broad conditions: analytical validity, clinical validity, clinical utility and a reasonable cost for genetic analysis are not yet accessible.

Keywords: Bipolar disorder, Genome-Wide Association Studies (GWAS), Candidate genes, Polymorphisms, Molecular beacons, Mutations.