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We hypothesized that variants in\n                      <jats:italic>FTO, LEP, LEPR, ADRB3, ADIPOQ<\/jats:italic>\n                      ,\n                      <jats:italic>TCF7L2<\/jats:italic>\n                      ,\n                      <jats:italic>ENPP1<\/jats:italic>\n                      ,\n                      <jats:italic>APOA5, PPARG<\/jats:italic>\n                      , and\n                      <jats:italic>CYP11B2<\/jats:italic>\n                      are associated with MetS and obesity-related traits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A group of 420 subjects (179 with MetS and 241 without MetS) was selected from a Brazilian adult cohort. Clinical, anthropometric, metabolic and inflammatory data were assessed. Genetic variants were analyzed by qPCR and their association with non-genetic variables were explored using multivariate logistic and linear regression analyses. Using logistic regression results weighted by clinically relevant variants, we evaluated the prognostic capability of a polygenic risk score (PRS) model for MetS risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ADRB3<\/jats:italic>\n                      rs4994A&gt;G (OR:3.71, 95%CI:1.71-8.03,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and\n                      <jats:italic>LEPR<\/jats:italic>\n                      rs1137100A&gt;G (OR: 2.52, 95%CI: 1.33-4.79,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005) were associated with high risk of MetS.\n                      <jats:italic>ADRB3<\/jats:italic>\n                      rs4994A&gt;G,\n                      <jats:italic>LEPR<\/jats:italic>\n                      rs1137100A&gt;G,\n                      <jats:italic>FTO<\/jats:italic>\n                      rs17817449T&gt;G and\n                      <jats:italic>PPARG<\/jats:italic>\n                      rs1801282C&gt;G predicted anthropometric, metabolic and inflammatory alterations related to MetS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Normalized values of PRS (nPRS) were higher in subjects with MetS, although ROC analysis demonstrated to discriminate MetS with limited sensitivity (AUC-ROC\u2009=\u20090.616,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), increasing values of nPRS were associated with higher number of MetS components (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Variants in\n                      <jats:italic>ADRB3, LEPR<\/jats:italic>\n                      ,\n                      <jats:italic>FTO<\/jats:italic>\n                      and\n                      <jats:italic>PPARG<\/jats:italic>\n                      play an important role in adiposity related to MetS, contributing to metabolic disturbances and pro-inflammatory state that increase cardiovascular risk in adult subjects. The integration of these variants into a polygenic risk score highlights a cumulative genetic susceptibility, as reflected by higher scores in MetS and a clear gradient across the number of MetS components.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41366-026-02218-9","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:16:36Z","timestamp":1789992996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ADRB3, LEPR, FTO and PPARG variants contribute to obesity-related metabolic syndrome in Brazilian adults: a polygenic risk score approach"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8945-9928","authenticated-orcid":false,"given":"Tamiris Invencioni Moraes","family":"Stefani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3967-8121","authenticated-orcid":false,"given":"Thiago Dominguez Crespo","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-8332","authenticated-orcid":false,"given":"Alvaro","family":"Cerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1253-9728","authenticated-orcid":false,"given":"Raquel","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8579-8981","authenticated-orcid":false,"given":"Marina Aparecida","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1847-8910","authenticated-orcid":false,"given":"Cristina Moreno","family":"Fajardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-360X","authenticated-orcid":false,"given":"Eg\u00eddio Lima","family":"Dorea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2315-6938","authenticated-orcid":false,"given":"M\u00e1rcia Martins Silveira","family":"Bernik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9521-7979","authenticated-orcid":false,"given":"Mario Hiroyuki","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3073-5967","authenticated-orcid":false,"given":"Rosario Dominguez Crespo","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2218_CR1","doi-asserted-by":"publisher","first-page":"786","DOI":"10.3390\/ijms23020786","volume":"23","author":"G Fahed","year":"2022","unstructured":"Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M, Bouferraa Y, et al. 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