At least a part of RA risk could be explained by gene–gene and gene-environment interactions. There are currently more than 150 candidate loci with polymorphisms that associate with RA, mainly related to seropositive disease, and new discoveries are anticipated in the future from investigation of diverse human populations.

Hereditary spherocytosis is characterized by hemolysis of spheroidal RBCs and anemia. Hereditary elliptocytosis (ovalocytosis) is a rare autosomal dominant disorder in which RBCs are oval or elliptical. Hemolysis is usually absent or slight, with little or no anemia except in some homozygous patients (hereditary pyropoikilocytosis). Pathophysiology