Genetics of psoriasis

Abstract

Psoriasis has long been considered a genetic disorder. The fi rst observation that psoriasis is an inherited, familial skin disorder was made in 1957. Extensive epidemiologic evidence and monozygotic twin concordance studies confi rmed familial clustering of this chronic infl ammatory disease and drove scientifi c investigation into the genetic basis of psoriasis. Since 1957, the list of psoriasis-associated genetic polymorphisms, including some rare causal mutations, has grown tremendously due to advanced high-throughput genotyping platforms and statistical methods. Nevertheless, the majority of psoriasis patients lack known psoriasis- associated susceptibility loci and the exact molecular mechanisms by which polymorphisms contribute to psoriasis remains poorly understood. Recent work points to a complex interplay between genetics, epigenetics, and the infl ammatory signaling networks of skin and immune cell mediators. In contrast, other mutations appear to be causative, such as the recently identifi ed mutations in IL36RN and CARD14, and shed light on new immunologic pathways driving pustular psoriasis. Evidence is also rapidly accumulating for the role of epigenetic changes in psoriasis heritability. The decreasing cost and rapid advancements in genetic technologies in combination with the formation of multi-institutional patient registries will likely result in a better understanding of the “missing heritability” in psoriasis and other complex, multigenic diseases.