Functional enrichment analysis was conducted to test whether high-priority genes identified in the fine-mapping results were expressed in specific tissue types or enriched in certain cell types or gene pathways. High-priority genes were defined as those mapped from variants in credible intervals containing less than five variants. That is, for each variant in credible intervals with less than five variants, we used the UCSC genome annotation database to assign genes. We assigned intergenic variants to the nearest gene. We mapped genes from variants with PIP < 0.01 (as ‘control’ genes) in the same way. Functional enrichment was then evaluated by estimating a relative risk (as described and implemented previously52), defined as the ratio of the proportion of genes mapped from variants in credible intervals with less than five variants that are in a given annotation category to the proportion of genes mapped from variants, within associated loci, with PIP < 0.01 in the same annotation category. Annotation categories were derived from GTEx tissue expression53, central nervous systems cell types50 and gene pathways54.
