Abstract
This study aims at assessing the burden of rare (minor allele frequency < 1%) predicted damaging variants in the whole exome of 92 bipolar I disorder (BD) patients and 1051 controls of French ancestry. Patients exhibiting an extreme phenotype (earlier onset and family history of mood disorder) were preferentially included to increase the power to detect an association. A collapsing strategy was used to test the overall burden of rare variants in cases versus controls at the gene level. Only protein-truncating and predicted damaging missense variants were included in the analysis. Thirteen genes exhibited p values exceeding 10−3 and could be considered as potential risk factors for BD. Furthermore, the validity of the association was supported when the Exome Aggregation Consortium database non-Finnish European population was used as controls for eight of them. Their gene products are involved in various cerebral processes, some of which were previously implicated in BD and belong to pathways implicated in the therapeutic effect of lithium, the main mood stabilizer. However, exome-wide threshold for association study was not reached, emphasizing that larger samples are needed.
Highlights
Introduction BipolarI disorder (BD) is a chronic psychiatric illness characterized by mood oscillations, with episodes of mania and depression
This study aims at comparing the burden of rare predicted damaging variants in the whole exome between bipolar I disorder (BD) and controls at the gene level
Patients were prescreened according to the MINI scale (Mini International Neuropsychiatric Interview) according to DSM-IV-TR criteria and underwent a comprehensive clinical examination including the assessment of the Diagnostic Interview for Genetic Studies scale[11] and psychiatric family history through Affective Disorder Evaluation[12]
Summary
Introduction BipolarI disorder (BD) is a chronic psychiatric illness characterized by mood oscillations, with episodes of mania and depression. Twin, and adoption studies have provided strong evidence for the importance of genetic factors in the etiology of BD2. Linkage studies in multiplex families identified mostly non-replicated findings[3]. Mendelian genes are unlikely to be involved in BD. Genome-wide association studies (GWAS) identified several significantly associated loci carrying common variants that explain altogether only a small fraction of the genetic component of BD5. It has been hypothesized that for complex diseases such as BD, rare non-synonymous coding variants of moderateto-large effect might explain a substantial part of the socalled missing heritability[6]. With the development and generalization of massive parallel sequencing, it is possible to assess this hypothesis at the scale of all 20,000 human genes by whole-exome sequencing (WES)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
