Abstract
Bipolar disorder is a common, chronic psychiatric disorder. Despite high heritability, there is a paucity of identified genetic risk factors. Immune biomarkers are under more direct genetic influence than bipolar disorder. To explore the genetic associations with immune biomarker levels in cerebrospinal fluid (CSF) and blood serum which previously showed differences in bipolar disorder, we performed a study involving 291 individuals (184 bipolar disorder patients and 107 controls). The biomarkers assayed in both CSF and serum were: chitinase-3-like protein-1 (YKL-40), monocyte chemoattractant protein-1 (MCP-1), soluble cluster of differentiation (sCD14), tissue inhibitor of metalloproteinases-1 and 2 (TIMP-1 and TIMP-2). C-reactive protein (CRP) was only quantified in serum, and interleukin 8 (IL-8) measures were only available in CSF. Genome-wide association studies were conducted using PLINK for each of three genotyping waves and incorporated covariates for population substructure, age, sex, and body mass index (BMI). Results were combined by meta-analysis. Genome-wide significant associations were detected for all biomarkers except TIMP-1 and TIMP-2 in CSF. The strongest association in CSF was found for markers within the CNTNAP5 gene with YKL-40 (rs150248456, P = 2.84 × 10−10). The strongest association in serum was also for YKL-40 but localized to the FANCI gene (rs188263039, P = 5.80 × 10−26). This study revealed numerous biologically plausible genetic associations with immune biomarkers in CSF and blood serum. Importantly, the genetic variants regulating immune biomarker levels in CSF and blood serum differ. These results extend our knowledge of how biomarkers showing alterations in bipolar disorder are genetically regulated.
Highlights
Bipolar disorder is a chronic psychiatric disorder characterized by recurrent episodes of mania or hypomania and depression that afflicts about 60 million people worldwide[1,2,3]
cerebrospinal fluid (CSF) concentration of YKL40 differs between bipolar cases and controls[20], genes are likely to regulate the expression of biomarkers in people with and without bipolar disorder in a similar way
A previous genome-wide association studies (GWAS) of bipolar disorder in Norwegian individuals followed by replication in Icelandic samples found nominally significant (P < 0.05) markers located in this gene area[39]
Summary
Bipolar disorder is a chronic psychiatric disorder characterized by recurrent episodes of mania or hypomania and depression that afflicts about 60 million people worldwide[1,2,3]. The etiopathogenesis of bipolar disorder is not fully understood. One line of research has explored immunoinflammatory processes in bipolar disorder and a number of studies have investigated immune markers in serum[12,13,14,15,16]. Not necessarily indicative of immune and inflammatory activity in the brain. This is because concentrations of cytokines and other proteins in serum or plasma come from production in peripheral tissues and do not reflect inflammatory processes in the brain[17,18,19]. We previously investigated a set of immune biomarkers in cerebrospinal fluid (CSF) in bipolar disorder
Sign-in/Register to view highlights & summary 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.
