Sham, 2011), are based on the degree of genetic relatedness among individuals from different families of origin that is due to measured genetic variants, as opposed to the degree of genetic relatedness implied by different familial relationships (monozygotic twin siblings, dizygotic twins or other sibling pairs, parent-offspring pairs, and the like). GREML determines the degree to which genetic relatedness between pairs of individuals accounts for phenotypic variance, using a mixed model to estimate the genetic variance in the phenotype. Because subjects are not from the same family, phenotypic similarity between them cannot be due to the collection of factors that contribute to family resemblance, including shared environment. It must be due to genetic variants inherited independently by subjects who are unrelated by kinship that influence the trait under study or that are linked with causal variants. Endophenotype research can be extended by GREML in ways that are not possible with classic twin- or family-based methods, such as to partition heritability by different characteristics of the genome, such as chromosome, minor allele frequency, and functional annotation, a method of attaching relevant biological information to genomic elements. (See J. J. Lee, Vattikuti, & Chow, 2016, for a discussion.) GREML also can be
