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© 2016 Elsevier Ltd All rights reserved. The evolution of the human immune system reflects the need to balance defense against constantly evolving pathogens and maintenance of self-tolerance. Evidence for the role of genetics in common complex autoimmune disease comes from several sources. Relatives of patients with autoimmune disease are more likely than the general population to have the same or another autoimmune condition, indicating shared genetic predispositions; an association between HLA alleles and autoimmunity has long been recognized and increasing numbers of disease associated non-HLA variants are being revealed by genome-wide studies. However, not all the variation in individual susceptibility can be explained by our current understanding of genetics. Future studies need to address this missing heritability, in the context of environmental and other chance events. Environmental effects interact with genetic predisposition, in some cases by epigenetic effects; complexity is increased by epistasis, structural and rare variants. Mechanistic insights from systems biology are beginning to illuminate the functional effects of genetic modifications, and suggest potential targets for more effective therapeutics.

Original publication





Book title

Encyclopedia of Immunobiology

Publication Date





133 - 141