Furthermore, it has been shown that some (both heterozygous and homozygous) APOE variant combinations are disruptive enough to lead to the development of a lipid storage phenotype in humans, characterized by dysbetalipoproteinemia, and splenomegaly, caused by accumulation of foam cells/sea-blue histiocytes in the spleen [1,8,12,21,43]. Here, APOE is linked to Splenomegaly.