RAREMETAL works in two steps. The first step, implemented in RAREMETALWORKER (RMW), analyzes individual studies and generates summary statistics that can later be combined across studies. This step can account for relatedness among individuals or hidden population structure using a variance component approach, based on either a kinship matrix estimated from pedigree (Abecasis et al., 2002) or a genomic relationship matrix estimated from marker data (Kang et al., 2010; Lippert et al., 2011). When chromosome X is analyzed, an additional variance component is used to describe kinship for X-linked markers.
