Figure 1: Study design.
From: Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles
Our study design consisted of looking for genetic associations with CIAG across the minor allele frequency spectrum. (a) First, we recruited CIAG cases (red circle) and both treated and untreated controls (blue circles). Next, we used multiple technologies to genotype variants including genotyping arrays for both common and rare variants, whole-exome sequencing, imputation of classical HLA four-digit alleles and amino acids in the major histocompatibility complex, and copy number variants. Finally, we performed association tests for each class of variants. Results that exceeded the multiple-testing threshold are coloured in yellow. References to figures and tables are listed in blue italics. (b) We used multiple technologies to genotype variants including whole-exome sequencing (green), exome array (pink), OmniExpress (blue) and Illumina 550K genome-wide arrays (orange). In addition, we used allele counts from the Exome Sequencing Project as extra control chromosomes (purple). As demonstrated by the Venn diagrams, the majority of cases (n=163) and treated controls (n=250) were genotyped on more than one platform.
