{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:16Z","timestamp":1785421696668,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007194","name":"Universidad de Santiago de Chile","doi-asserted-by":"crossref","award":["USA2456_2025"],"award-info":[{"award-number":["USA2456_2025"]}],"id":[{"id":"10.13039\/100007194","id-type":"DOI","asserted-by":"crossref"}]},{"award":["USA2456_2025"],"award-info":[{"award-number":["USA2456_2025"]}],"id":[{"id":"https:\/\/ror.org\/02ma57s91","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ANID Programa Becas Doctorado Nacional 2020","award":["1690\/2022"],"award-info":[{"award-number":["1690\/2022"]}]},{"name":"ANID-Fondecyt","award":["1230980"],"award-info":[{"award-number":["1230980"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Idiopathic Parkinson\u2019s disease (iPD) represents the most prevalent form of Parkinson\u2019s disease; however, the molecular mechanisms underlying its development remain only partially understood. N6-methyladenosine (m6A), the most abundant internal RNA modification in eukaryotic mRNA, has emerged as a key regulator of gene expression and has been implicated in neurodegenerative disorders. In this study, we performed integrated differential expression, weighted gene co-expression network analysis (WGCNA), and differential co-expression (DECO) analyses using peripheral blood RNA-seq data from Latin American controls and early iPD patients to investigate m6A-associated transcriptional alterations. WGCNA and differential expression analyses identified 1207 hub genes and 237 differentially expressed genes, respectively. The integration of these datasets with curated m6A-related genes yielded 12 overlapping candidate genes associated with early iPD. Subsequent DECO analysis revealed three significant m6A regulator\u2013target differential co-expression links involving the m6A factors VIRMA, YTHDF3, and HNRNPA2B1. Experimental validation in an independent exploratory cohort confirmed altered expression of these regulators and increased m6A enrichment of NRCAM and PKHD1 transcripts. To our knowledge, this study represents the first integrative transcriptomic evaluation of m6A-associated regulatory patterns in early iPD within a Latin American population. Collectively, our findings suggest that selective m6A-associated transcriptional network alterations may contribute to the systemic molecular signatures observed in early iPD, warranting further validation in larger and mechanistically oriented studies.<\/jats:p>","DOI":"10.3390\/life16040592","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:09:54Z","timestamp":1775138994000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Weighted Gene Co-Expression Network and Differential Expression Analyses to Unveil the Role of RNA m6A Methylation Regulators in Idiopathic Parkinson\u2019s Disease in Latin America"],"prefix":"10.3390","volume":"16","author":[{"given":"Francisco","family":"Leiva","sequence":"first","affiliation":[{"name":"Laboratory of Genomics, Molecular Ecology and Evolutionary Studies, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-0119","authenticated-orcid":false,"given":"Luis","family":"Constandil","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9946-3299","authenticated-orcid":false,"given":"Pedro","family":"Chana-Cuevas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Santiago of Chile, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-7387","authenticated-orcid":false,"given":"Rene L.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Center for Integrative Biology, Universidad Mayor, Santiago 7510041, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-7480","authenticated-orcid":false,"given":"Bernardo","family":"Morales","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-959X","authenticated-orcid":false,"given":"Rodrigo","family":"Vidal","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics, Molecular Ecology and Evolutionary Studies, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7229","DOI":"10.1007\/s12035-018-0907-1","article-title":"Whole-Transcriptome Analysis of Mouse Models with MPTP-Induced Early Stages of Parkinson\u2019s Disease Reveals Stage-Specific Response of Transcriptome and a Possible Role of Myelin-Linked Genes in Neurodegeneration","volume":"55","author":"Alieva","year":"2018","journal-title":"Mol. 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