{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:03:29Z","timestamp":1791813809336,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Non\u2010invasive diagnostics for metabolic dysfunction\u2013associated fatty liver disease (MAFLD) remain challenging. We aimed to identify novel key genes as non\u2010invasive biomarkers for MAFLD, elucidate causal relationships between biomarkers and MAFLD and determine the role of immune cells as potential mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Utilizing published transcriptome data of patients with biopsy\u2010proven MAFLD, we applied linear models for microarray data, least absolute shrinkage and selector operation (LASSO) regressions and receiver operating characteristic (ROC) curve analyses to identify and validate biomarkers for MAFLD. Using the expression quantitative trait loci database and a cohort of 778\u2009614 Europeans, we used Mendelian randomization to analyse the causal relationships between key biomarkers and MAFLD. Additionally, mediation analysis was performed to examine the involvement of 731 immunophenotypes in these relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 31 differentially expressed genes, and LASSO regression showed three hub genes,\n                      <jats:italic>IGFBP2<\/jats:italic>\n                      ,\n                      <jats:italic>PEG10<\/jats:italic>\n                      , and\n                      <jats:italic>P4HA1<\/jats:italic>\n                      , with area under the receiver operating characteristic (AUROC) curve of 0.807, 0.772 and 0.791, respectively, for identifying MAFLD. The model of these three genes had an AUROC of 0.959 and 0.800 in the development and validation data sets, respectively. This model was also validated using serum\u2010based enzyme\u2010linked immunosorbent assay data from MAFLD patients and control subjects (AUROC: 0.819, 95% confidence interval: 0.736\u20130.902).\n                      <jats:italic>PEG10<\/jats:italic>\n                      was associated with an increased MAFLD risk (odds ratio\u2009=\u20091.106,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032) via inverse variance\u2013weighted analysis, and about 30% of this risk was mediated by the percentage of CD11c\u2009+\u2009CD62L\u2013 monocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The MAFLD panels have good diagnostic accuracy, and the causal link between\n                      <jats:italic>PEG10<\/jats:italic>\n                      and MAFLD was mediated by the percentage of CD11c\u2009+\u2009CD62L\u2013 monocytes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15925","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T03:38:38Z","timestamp":1725421118000},"page":"5590-5599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Causal relationship between key genes and metabolic dysfunction\u2010associated fatty liver disease risk mediated by immune cells: A Mendelian randomization and mediation analysis"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-0029","authenticated-orcid":false,"given":"Gong","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Institute of General Practice Xi'an Medical University  Xi'an 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