Genetic Influences On Inflammatory Biomarkers In Bipolar Disorder

Abstract

Background Inflammatory mechanisms have been implicated in the pathophysiology and progression of bipolar disorder. Markers of inflammation circulating in blood are often used in these investigations, but demonstrate little relationship to central nervous system inflammation and related biomarkers in the cerebrospinal fluid (CSF). This study investigates the genetic mediation of inflammation biomarkers in CSF and serum from subjects with bipolar disorder and healthy controls. Methods Subjects were drawn from the St. Goran Bipolar Project which enrolls patients from bipolar disorder clinics in Gothenburg and Stockholm in addition to age and sex-matched healthy controls. For the inflammation-related biomarkers YKL40, MCP1, sCD14, TIMP1, and TIMP2, CSF and serum levels were quantified, as well as CSF levels of IL8 and serum levels of CRP and MMP9. Subjects were genotyped using the Affymetrix 6.0 and Illumina OmniExpress arrays. Genome-wide association studies of these biomarkers were conducted for the 51-57 controls and 101-164 cases with available data using PLINK and included covariates for age, sex, and principle components accounting for population substructure. Results Genome-wide significant associations (p Discussion Levels of inflammatory biomarkers in CSF and serum are both genetically mediated but probably differentially. The associated genetic markers, in conjunction with the biomarker levels previously associated with bipolar disorder, could be used to aid diagnoses and as possible targets for the development of novel therapeutics.