Fig. 9: Effects of multiple sclerosis (MS) covariates on cerebrospinal fluid (CSF) biomarkers.

a Association of the CSF proteome with body mass index (BMI) was tested using BMI as a continuous and categorical variable (normal <30, obese ≥30), yielding comparable results. b Volcano plot of somamer associations with BMI (continuous). Circle colors highlight proteins linked to lipid metabolism (blue), axon guidance/synapses (purple), pro-inflammatory molecules (red), and pathways/clusters (gray). Vertical gray line = coefficient of 0; dashed blue line = unadjusted p ≤ 0.05. The insert shows the correlation of BMI with leptin (LEP) levels adjusted for healthy control (HC) age and sex. Female samples (pink circles) and male samples (blue triangles) are shown with sex-specific regression lines and 95% confidence intervals (CIs) characterized by Pearson correlation coefficient (R) and unadjusted p-value. c Examples of BMI-associated somamers. Top: scatter plot of BMI and HC-adjusted C-reactive protein (CRP) levels shows a significant association without sex effect. Bottom: boxplot shows significant differences in NEO1 between normal and obese BMI categories. Females shown as pink circles, males as blue triangles. Significance tested by two-sided Wilcoxon rank-sum test. Boxplots display medians, quartiles, and whiskers (1.5 × interquartile range [IQR]). Gray dashed lines show HC means. d Association of somamers with HLA-DRB1*15:01/03 haplotype tested by regression across three genotypes. One-sided Chi-squared analysis (false discovery rate [FDR]-adjusted) revealed enrichment of astrocyte-, neuronal-, oligodendrocyte-, oligodendroglial precursor cell (OPC)-, endothelial-, microglia-, and plasma cell–specific proteins in homozygous carriers of the susceptibility allele. e Examples: DSCAM positively, PLK1 negatively associated with DRB115:01/03 haplotype. Female (pink circles) and male (blue triangles) samples shown; significance tested by two-sided one-way ANOVA. Boxplots as in (c), with gray dashed lines marking HC means. f Ingenuity Pathway Analysis (IPA) predictions of processes activated (orange) or inhibited (blue) from DRB1*15:01/03-associated proteins. Bar length indicates activation z score; green dots show –log10 p-values. All p-values of regression coefficients were tested in a two-sided test.