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Our objective was to determine whether genetic variants are associated with pain and disease activity in rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants were included from two independent RA cohorts: FORWARD (National Databank for Rheumatic Diseases, training data set) and the Veterans Affairs Rheumatoid Arthritis Registry (VARA; validation data set). Multivariable linear regression was used to estimate the relationship between cross\u2010sectional pain scores and 36 fibromyalgia (FM)\u2013associated SNPs in FORWARD. SNP alleles were summed and weighted by these regression coefficients to generate a genetic risk score (GRS) for pain for each participant in both cohorts. Linear regressions and generalized estimating equations were used to determine the relationship between this GRS, an existing pain intensity GRS, and pain and self\u2010reported disease activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The sample comprised 756 participants from FORWARD (mean age 56.8 years, 89.4% female) and 2,176 participants from VARA (mean age 64.3 years, 11.0% female) who had pain and genotyping data. Participants in the validation data set (VARA) with FM GRS in the highest quartile had more baseline pain than those in the lowest quartile (+0.55 [95% confidence interval 0.16\u20130.93],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006). This was also true for the existing pain intensity GRS. VARA participants in the highest quartile of both GRS had more pain throughout follow\u2010up and higher disease activity scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GRS based on pain\u2010related SNPs were associated with RA pain and disease activity, suggesting that the genetic risk of pain may have clinical impacts in RA, such as the likelihood of achieving remission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr.25588","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T04:04:54Z","timestamp":1751256294000},"page":"1409-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and External Validation of a Genetic Risk Score for Pain in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-9122","authenticated-orcid":false,"given":"Katie J.","family":"McMenamin","sequence":"first","affiliation":[{"name":"Boston Medical Center  Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0194-7562","authenticated-orcid":false,"suffix":"IV","given":"Thomas R.","family":"Riley","sequence":"additional","affiliation":[{"name":"University of Pennsylvania and Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center  Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8137-8117","authenticated-orcid":false,"given":"Kristin","family":"Wipfler","sequence":"additional","affiliation":[{"name":"FORWARD, The National Databank for Rheumatic Diseases  Wichita Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaleb","family":"Michaud","sequence":"additional","affiliation":[{"name":"FORWARD, The National Databank for Rheumatic Diseases, Wichita, Kansas, and VA Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center  Omaha"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8816-7782","authenticated-orcid":false,"given":"Austin","family":"Wheeler","sequence":"additional","affiliation":[{"name":"VA Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center  Omaha"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-3588","authenticated-orcid":false,"given":"Bryant R.","family":"England","sequence":"additional","affiliation":[{"name":"VA Nebraska\u2010Western Iowa Health Care System and University of Nebraska Medical Center  Omaha"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-3051","authenticated-orcid":false,"given":"Brian","family":"Sauer","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center and University of Utah  Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8707-7649","authenticated-orcid":false,"given":"Katherine D.","family":"Wysham","sequence":"additional","affiliation":[{"name":"VA Puget Sound Health Care System and University of Washington  Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Xiao","sequence":"additional","affiliation":[{"name":"University of Pennsylvania and Children's Hospital of Philadelphia  Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"March","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-9173","authenticated-orcid":false,"given":"Grant W.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center and University of Utah  Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvanus","family":"Toikumo","sequence":"additional","affiliation":[{"name":"University of Pennsylvania and Corporal Michael J. 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