Editing Psoriasis (section)

===Genetics===
{{See also|List of human leukocyte antigen alleles associated with cutaneous conditions}}
Around one-third of people with psoriasis report a [[family history (medicine)|family history]] of the disease, and researchers have identified genetic [[locus (genetics)|loci]] associated with the condition. [[twin|Identical twin]] studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for fraternal twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.<ref name=Krueger>{{cite journal | vauthors = Krueger G, Ellis CN | title = Psoriasis--recent advances in understanding its pathogenesis and treatment | journal = Journal of the American Academy of Dermatology | volume = 53 | issue = 1 Suppl 1 | pages = S94–100 | date = July 2005 | pmid = 15968269 | doi = 10.1016/j.jaad.2005.04.035 }}</ref>

Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the [[immune system]], particularly the [[major histocompatibility complex]] (MHC) and [[T cells]]. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.<ref name=Nestle>{{cite journal | vauthors = Nestle FO, Kaplan DH, Barker J | title = Psoriasis | journal = The New England Journal of Medicine | volume = 361 | issue = 5 | pages = 496–509 | date = July 2009 | pmid = 19641206 | doi = 10.1056/NEJMra0804595 | s2cid = 203791161 | doi-access = free }}</ref>

Classic genome-wide [[linkage analysis]] has identified nine loci on different [[chromosome]]s associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (''[[PSORS1]]'' through ''PSORS9''). Within those loci are genes on pathways that lead to inflammation. Certain variations ([[mutation]]s) of those genes are commonly found in psoriasis.<ref name=Nestle/> [[Genome-wide association study|Genome-wide association scans]] have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal [[proteins]], which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.<ref name=Nestle/>

The major determinant is ''PSORS1'', which probably accounts for 35–50% of psoriasis heritability.<ref>{{cite journal | vauthors = Smith CH, Barker JN | title = Psoriasis and its management | journal = BMJ | volume = 333 | issue = 7564 | pages = 380–4 | date = August 2006 | pmid = 16916825 | pmc = 1550454 | doi = 10.1136/bmj.333.7564.380 }}</ref> It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. ''PSORS1'' is located on [[chromosome 6]] in the MHC, which controls important immune functions. Three genes in the ''PSORS1'' locus have a strong association with psoriasis vulgaris: ''HLA-C'' variant ''HLA-Cw6'',<ref name="Prieto2013"/> which encodes an MHC class I protein; ''[[CCHCR1]]'', variant WWC, which encodes a [[coiled coil]] protein overexpressed in psoriatic [[epidermis]]; and ''[[CDSN]]'', variant allele 5, which encodes [[corneodesmosin]], a protein expressed in the granular and [[cornified layer]]s of the epidermis and upregulated in psoriasis.<ref name=Nestle/>

Two major immune system genes under investigation are interleukin-12 subunit beta (''IL12B'') on [[Chromosome 5 (human)|chromosome 5q]], which expresses interleukin-12B; and ''[[IL23R]]'' on chromosome 1p, which expresses the interleukin-23 receptor and is involved in T cell differentiation. Interleukin-23 receptor and ''IL12B'' have both been strongly linked with psoriasis.<ref name="Prieto2013"/> T cells are involved in the inflammatory process that leads to psoriasis.<ref name=Nestle/> These genes are on the pathway that upregulates tumor necrosis factor-α and [[NF-κB|nuclear factor κB]], two genes involved in inflammation.<ref name=Nestle/> The first gene directly linked to psoriasis was identified as the ''[[CARD14]] ''gene located in the ''PSORS2'' locus. A rare mutation in the gene encoding for the ''[[CARD14]]''-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).<ref name = Jordan1>{{cite journal | vauthors = Jordan CT, Cao L, Roberson ED, Duan S, Helms CA, Nair RP, Duffin KC, Stuart PE, Goldgar D, Hayashi G, Olfson EH, Feng BJ, Pullinger CR, Kane JP, Wise CA, Goldbach-Mansky R, Lowes MA, Peddle L, Chandran V, Liao W, Rahman P, Krueger GG, Gladman D, Elder JT, Menter A, Bowcock AM | title = Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis | journal = American Journal of Human Genetics | volume = 90 | issue = 5 | pages = 796–808 | date = May 2012 | pmid = 22521419 | pmc = 3376540 | doi = 10.1016/j.ajhg.2012.03.013 }}</ref><ref name = Jordan2>{{cite journal | vauthors = Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, Ryan C, Duan S, Helms CA, Liu Y, Chen Y, McBride AA, Hwu WL, Wu JY, Chen YT, Menter A, Goldbach-Mansky R, Lowes MA, Bowcock AM | title = PSORS2 is due to mutations in CARD14 | journal = American Journal of Human Genetics | volume = 90 | issue = 5 | pages = 784–95 | date = May 2012 | pmid = 22521418 | pmc = 3376640 | doi = 10.1016/j.ajhg.2012.03.012 }}</ref>