Fig. 6: Quantification of APOE intron-3 retaining transcript usage.

Quantification of intron retention usage by its normalised coverage to junction ratio across brain tissues within GTEx (a). Normalised coverage to junction ratio of the APOE intron-3 retention event in bulk RNA-sequencing data of post-mortem dorsolateral prefrontal cortex tissue samples from 634 individuals recruited within ROSMAP studies across Braak and Braak staging (b) and APOE ɛ4 allele status (c). In a, red dashed horizontal line presents the median normalised intron retention coverage to junction ratio within central nervous system tissues in GTEx. Number of samples within each of the tissue groups was as follows: amygdala—72; anterior cingulate cortex—84; caudate—117, cerebellar hemisphere—105; frontal cortex—108; hippocampus—94; hypothalamus—96; nucleus accumbens—113; putamen—97; spinal cord—71; substantia nigra—63. The Kruskal–Wallis p value show results from comparison of the differences in the normalised intron retention coverage to junction ratio between the different brain regions with pairwise regions comparisons shown in Supplementary Table 6. In b and c, the blue line represents the linear regression fit with the grey shaded area representing ± 95% confidence interval. Braak and Braak staging is a measure of severity of neurofibrillary tangle based on location. To improve the power of the study, we merged Braak and Braak stages I and II to “Braak mild stage”, Braak and Braak stages III and IV to “Braak moderate” and Braak and Braak stages V and VI to indicate “Braak severe” stage. For number of APOE ɛ4 alleles, a heterozygous state is represented by “1” and homozygous state by “2”.