{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T02:22:49Z","timestamp":1767666169095,"version":"3.37.3"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4\/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated variants and of CD4\/CD8 ratio in sarcoidosis phenotypes, L\u00f6fgren\u2019s syndrome (LS) and non- L\u00f6fgren\u2019s syndrome (non-LS). We employed a polygenic-based approach using genome-wide association studies results on relative levels of T-cells in healthy individuals to measure the genetic contribution of T-cells in sarcoidosis entities. Results revealed that the genetic architecture of LS is highly influenced by genetic variants associated with CD8+ T-cells and CD4\/CD8 ratio, explaining up to 7.94% and 6.49% of LS variation, respectively; whereas, the genetic architecture of non-LS is minimally influenced by T-cells, explaining a phenotypic variation of &lt;1%. Moreover, pleiotropy assessment between T-cells and LS\/non-LS associated-variants led to the discovery of highly scored pathway maps that shared common factors related to antigen presentation and T-cell regulatory mechanisms. Differences in significant polygenic scores, presence of pleiotropy, and distinct genetic factors provide further insights on how genetic variants and genes associated with relative levels of T-cell subtypes contribute differently to sarcoidosis phenotypes.<\/jats:p>","DOI":"10.1038\/s41598-017-05754-7","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T14:02:08Z","timestamp":1499781728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-1243","authenticated-orcid":false,"given":"Natalia V.","family":"Rivera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-8216","authenticated-orcid":false,"given":"Michael","family":"Hagemann-Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel A. R.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Kullberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2950-5670","authenticated-orcid":false,"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Grunewald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,7,17]]},"reference":[{"key":"5754_CR1","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1378\/chest.104.2.352","volume":"104","author":"RH Winterbauer","year":"1993","unstructured":"Winterbauer, R. 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