Fig. 1

Trisomy 21 induces the kynurenine pathway. a Differentially abundant metabolites in plasma samples from individuals with T21 were identified using a linear model adjusting for age, sex, and cohort. Metabolites that increased in the T21 group are shown in red and metabolites that decreased in the T21 group are blue. The horizontal gray line represents an adjusted p-value of 0.05. n = 165 independent samples, 75 with T21. b Boxplots showing the relative quantification in log₂-adjusted intensity for significantly differentially abundant metabolites. p-values were calculated using the linear model from a and the FDR method for multiple testing correction. c Boxplots showing log₂-adjusted ratios as indicated. p-values were calculated using an unmoderated t-test on the linear model in a. d Boxplots showing concentrations of kynurenine and quinolinic acid, as well as the ratio of kynurenine to tryptophan calculated from the absolute quantification of these metabolites in Cohort 3, n = 124 independent samples, 72 with T21. e Scatter plots comparing kynurenine/tryptophan ratios with concentrations of quinolinic acid from Cohort 3. Spearman’s rho (ρ) and FDR-corrected p-values are indicated. f Boxplots showing concentrations of tryptophan, l-formylkynurenine, and kynurenine, as well as the ratio of kynurenine to tryptophan calculated from the absolute quantification of these metabolites in the CSF of Cohort 4, n = 100 independent samples, 50 with T21. All boxplots show median, 25th, and 75th percentile values. Error bars are 1.5 times the interquartile range (IQR) or the maximum data point if < 1.5 IQR