Fig. 1

Illustration of rare variant association analysis using Bin-KAT for neuroimaging genomics. First, rare variants were binned/collapsed based on biological knowledge, such as exon, gene, pathway, protein family, evolutionary conversed regions (ECR) or regulatory region, using BioBin. Then, statistical tests including a burden test and a dispersion test (SKAT), were incorporated into BioBin, called Bin-KAT [19]. Bin-KAT provides an option of performing unified rare variant association analysis methods in one tool to identify biologically-informed bins significantly associated with imaging endophenotypes of interest. VCF, variant call format