Editing Rheumatoid arthritis (section)

===Genetic===
Worldwide, RA affects approximately 1% of the adult population and occurs in one in 1,000 children. Studies show that RA primarily affects individuals between the ages of 40–60 years and is seen more commonly in females.<ref name=":14">{{cite journal | vauthors = Rennie KL, Hughes J, Lang R, Jebb SA | title = Nutritional management of rheumatoid arthritis: a review of the evidence | journal = Journal of Human Nutrition and Dietetics | volume = 16 | issue = 2 | pages = 97–109 | date = April 2003 | pmid = 12662368 | doi = 10.1046/j.1365-277x.2003.00423.x }}</ref><ref name=":16" /> A family history of RA increases the risk around three to five times; as of 2016, it was estimated that genetics may account for 40–65% of cases of seropositive RA, but only around 20% for seronegative RA.<ref name=Lancet2016/> RA is strongly associated with genes of the inherited tissue type [[major histocompatibility complex]] (MHC) antigen. [[HLA-DR4]] is the major genetic factor implicated – the relative importance varies across ethnic groups.<ref name="Elsevier"/>

[[Genome-wide association studies]] examining [[single-nucleotide polymorphism]]s have found around one hundred alleles associated with RA risk.<ref>{{cite journal | vauthors = Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Bridges SL, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapää-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M, Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K, Plenge RM | title = Genetics of rheumatoid arthritis contributes to biology and drug discovery | journal = Nature | volume = 506 | issue = 7488 | pages = 376–381 | date = February 2014 | pmid = 24390342 | pmc = 3944098 | doi = 10.1038/nature12873 | bibcode = 2014Natur.506..376. }}</ref> Risk alleles within the [[Human leukocyte antigen|HLA]] (particularly [[HLA-DRB1]]) genes harbor more risk than other loci.<ref>{{cite journal | vauthors = Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee HS, Jia X, Alfredsson L, Padyukov L, Klareskog L, Worthington J, Siminovitch KA, Bae SC, Plenge RM, Gregersen PK, de Bakker PI | title = Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis | journal = Nature Genetics | volume = 44 | issue = 3 | pages = 291–296 | date = January 2012 | pmid = 22286218 | pmc = 3288335 | doi = 10.1038/ng.1076 }}</ref> The HLA encodes proteins that control recognition of self- versus non-self molecules. Other risk loci include genes affecting co-stimulatory immune pathways{{em dash}}for example [[CD28]] and [[CD40]], cytokine signaling, lymphocyte receptor activation threshold (e.g., [[PTPN22]]), and innate immune activation{{em dash}}appear to have less influence than HLA mutations.<ref name=Lancet2016/><ref name="pmid131669381">{{cite journal | vauthors = Ghorban K, Ezzeddini R, Eslami M, Yousefi B, Sadighi Moghaddam B, Tahoori MT, Dadmanesh M, Salek Farrokhi A | title = PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a potential pathogenic mechanism in rheumatoid arthritis | journal = Immunology Letters | volume = 216 | pages = 106–113 | date = December 2019 | pmid = 31669381 | doi = 10.1016/j.imlet.2019.10.010 | s2cid = 204966226 }}</ref>

Despite the strong genetic components of the disease, [[Twin study|identical twin studies]] have shown only 12-15% concordance for twins raised in separate households. This indicates that rheumatoid arthritis most likely results from a combination of genetic and environmental factors, in a majority of cases.<ref>{{Cite journal |last1=Jang |first1=Sunhee |last2=Kwon |first2=Eui-Jong |last3=Lee |first3=Jennifer Jooha |date=2022-01-14 |title=Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells |journal=International Journal of Molecular Sciences |volume=23 |issue=2 |pages=905 |doi=10.3390/ijms23020905 |doi-access=free |issn=1422-0067 |pmc=8780115 |pmid=35055087}}</ref>