Figure 1.

Alteration of TCA Cycle Metabolites in CS, CS-like syndrome, or BRRS Cases Compared to Population Controls

A general logistic regression model was applied to evaluate the association between metabolite levels and genotype and/or phenotype, with age and gender as covariates. Heatmaps (A and F) depict TCA cycle metabolites (top label) and significance of associations relative to various phenotypic or genotypic group comparisons (left label). Blue color corresponds to an association with decreased metabolite levels, whereas orange color corresponds to an association with increased metabolite levels. Color intensity corresponds to different thresholds of p value significance (scale on the right).

(A) Heatmap depicting the association between TCA cycle metabolite levels and phenotypes, irrespective of genotype status, compared to population controls.

(B–E) Stratified gender depiction of increased citrate and lactate, but decreased isocitrate and succinate in all CS, CS-like syndrome, or BRRS cases (n = 511) compared to population controls (n = 98). Metabolite levels were log-transformed and center-scaled to have a mean of 0 and a standard deviation of 1. The line in the middle of each scatter plot is plotted at the mean. Error bars represent the 95% confidence intervals.

(F) Heatmap depicting the association between TCA cycle metabolite levels and genotypes, irrespective of phenotype status. The first three rows represent comparisons between individuals of different genotypes and population controls. The last two rows represent comparisons between individuals of various genotypes.