Chunk #40 — ONLINE METHODS — Data acquisition, quality control, and normalization — Association of intron usage with Alzheimer’s disease and neuropathology traits.
The association analysis with neuropathology traits and intron usage was performed using a linear model, adjusting for experimental batch, RNA integrity number (RIN), sex, age at death, and post-mortem interval (PMI). To test for association with Alzheimer’s disease, we limited the comparison to those participants clinical diagnosis of Alzheimer’s disease and those who have neither diagnosis (Supplementary Table 1). We used Leafcutter20 to identify intron clusters with at least one differentially excised intron by jointly modeling intron clusters using a Dirichlet-multinomial GLM20. To account for neuronal loss and cell type proportion in each brain sample, we used gene expression level of cell type specific genes as an additional covariate. However, these measures did not affect our association analysis. We report differentially spliced introns at Bonferroni-corrected P < 0.05 to correct for multiple hypothesis testing.
