{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:00:37Z","timestamp":1776852037287,"version":"3.51.2"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial dysfunction is implicated in asthma pathogenesis, but causal roles of mitochondrial\u2010related genes in paediatric asthma remain unclear. We performed a multi\u2010omics Mendelian randomization study integrating GWAS data from paediatric asthma cohorts with blood\u2010based methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs) and protein QTLs (pQTLs) datasets. Causal inference was assessed using Summary\u2010data\u2010based Mendelian Randomization (SMR) and HEIDI testing, complemented by colocalization analysis. Findings were validated in independent cohorts and evaluated for tissue specificity using GTEx. Functional enrichment and protein\u2013protein interaction (PPI) network analyses were conducted. SMR analysis identified 80 methylation sites spanning 54 genes, 26 gene expressions, and three proteins significantly associated with paediatric asthma. Colocalization analysis confirmed strong evidence for 10 methylation sites (7 genes), the\n                    <jats:italic>STX17<\/jats:italic>\n                    eQTL (PP.H4\u2009=\u20090.98) and the\n                    <jats:italic>UNG<\/jats:italic>\n                    pQTL (PP.H4\u2009=\u20090.84). Tissue\u2010specific eQTL validation replicated the\n                    <jats:italic>STX17<\/jats:italic>\n                    association. Multi\u2010omics integration associated\n                    <jats:italic>ALAS1<\/jats:italic>\n                    (cg13241645, cg15698299) and\n                    <jats:italic>TXNRD1<\/jats:italic>\n                    (cg09884423) with asthma at both methylation and expression levels, with colocalization supporting both\n                    <jats:italic>ALAS1<\/jats:italic>\n                    associations. Furthermore, integrated mQTL\u2010eQTL analysis suggests that DNA methylation potentially regulates\n                    <jats:italic>ALAS1<\/jats:italic>\n                    and\n                    <jats:italic>TXNRD1<\/jats:italic>\n                    expression. Functional enrichment and network analyses revealed that these candidate genes converge on mitochondrial metabolic pathways and identified seven hub genes with potential regulatory significance (\n                    <jats:italic>SDHB, MFN2, GLDC, PHB2, TXNRD1, ATP5MC1<\/jats:italic>\n                    and\n                    <jats:italic>PHB<\/jats:italic>\n                    ). This study provides multi\u2010omics evidence supporting a causal role for mitochondrial\u2010related genes, particularly\n                    <jats:italic>ALAS1<\/jats:italic>\n                    and\n                    <jats:italic>TXNRD1<\/jats:italic>\n                    , in paediatric asthma, offering new insights into pathogenesis and potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71102","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:01:01Z","timestamp":1774670461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria\u2010Related Pathogenic Genes in Paediatric Asthma: A Multi\u2010Omics Mendelian Randomization Study"],"prefix":"10.1111","volume":"30","author":[{"given":"Biyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4532-8800","authenticated-orcid":false,"given":"Yanming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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