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Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls

Journal article
Authors R. Y. Zhang
J. Song
Anniella Isgren
Joel Jakobsson
Kaj Blennow
C. M. Sellgren
Henrik Zetterberg
S. E. Bergen
Mikael Landén
Published in Translational Psychiatry
Volume 10
Issue 1
Pages 12
ISSN 2158-3188
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 12
Language en
Keywords c-reactive protein, weekly symptomatic status, genetic-variation, natural-history, association, loci, schizophrenia, identification, inflammation, pathways, Psychiatry
Subject categories Neurology


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=2.84x10(-10)). The strongest association in serum was also for YKL-40 but localized to the FANCI gene (rs188263039, P=5.80x10(-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.

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