Figure 3: Gene-burden test results.
From: Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles
We evaluated whether cases were more likely to carry rare functional variants in a gene compared with controls using sequencing data from 67 cases and 376 controls. Variants were annotated using the variant effect predictor tool and divided into three sets of severity. The most severe category consists of loss-of-function (LOF) variants annotated as being nonsense and splice site (green). The intermediate category included all LOF variants as well as missense variants annotated as probably damaging by PolyPhen-2 (magenta). The least severe category consisted of all LOF, missense and untranslated region (UTR) variants (blue). We had varying minor allele frequency (MAF) cutoffs with the most restrictive being 0–1% MAF and the most inclusive being 0–5%. For each MAF and variant set, we assessed whether any genes deviated from expectation as demonstrated by the diagonal line. The only gene that showed enrichment was BTNL2 (P=7.0 × 10−8, Fisher’s exact test).
