A splicing quantitative trait locus (sQTL) is a SNP that predicts alternative mRNA splicing associated with a trait. Similar to Li et al.23, we standardized excision-splicing ratios and then quantile normalized splicing data across individuals. Our analyses used default settings on MatrixQTL to find cis-acting sQTLs that may affect mRNA splicing in a nearby gene, which tests all SNPs within 1 megabase (Mb) of a genomic region. sQTLs were defined as a SNP associated with a differentially spliced gene that survived a BH-FDR correction for multiple testing per SNP. To determine whether sQTLs resided in specific regions of the genome we annotated sQTLs in 11 annotation categories from ANNOVAR (version 4.1)29. The annotation categories that were built on hg18 genome coordinates were updated to their corresponding hg19 values using CrossMap (version 0.5.1)30. Genetic analyses (polygenic score and sQTLs) controlled for sex, age, and two ancestral principal components.
