{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:36:47Z","timestamp":1768077407558,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7242065"],"award-info":[{"award-number":["7242065"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7244356"],"award-info":[{"award-number":["7244356"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lumbar disc degeneration (LDD) is a ubiquitous finding in low back pain. Many different etiology factors may explain the LDD process, such as bone morphogenetic proteins (BMPs), DNA methylation, and gut microbiota. Until recently the mechanisms underlying the LDD process have been elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BMP\u2010related genes were extracted from the GeneCards database. The LDD transcriptome dataset was obtained from the Gene Expression Omnibus. We used linear regression and meta\u2010analysis to screen and integrate the differentially expressed genes associated with BMPs in LDD. Genome\u2010wide association studies (GWASs) of LDD were from FinnGen and UKBB. The expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci from the blood were identified via the summary data\u2010based Mendelian randomization (SMR) method, and the possible blood BMP genes and their regulatory elements associated with the risk of LDD were prioritized. Intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated, and the potential interactions between BMP gene expression in host intestinal tissue and the gut microbiota were revealed through SMR and colocalization analysis. The GWAS catalog (GCST90246169) was used to validate SMR results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A meta\u2010analysis of five datasets revealed that 113 BMP genes were differentially expressed between LDD and control tissues. Seven genes were selected as candidate pathogenic genes of LDD via the three\u2010step SMR method: <jats:italic>CREB1<\/jats:italic>, <jats:italic>BMP6<\/jats:italic>, <jats:italic>PTCH1<\/jats:italic>, <jats:italic>GLI1<\/jats:italic>, <jats:italic>MEG3<\/jats:italic>, <jats:italic>GALNS<\/jats:italic>, and <jats:italic>NF1<\/jats:italic>. SMR analysis also revealed five possible gut genes: <jats:italic>HFE<\/jats:italic>, <jats:italic>MET<\/jats:italic>, <jats:italic>MAPK3<\/jats:italic>, <jats:italic>NPC1<\/jats:italic>, and <jats:italic>GDF5<\/jats:italic>. The correlation between the gut microbiota and BMP gene expression in intestinal tissues was verified by eQTL\u2010mbQTL colocalization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This multi\u2010omics study revealed that the BMP genes associated with LDD are regulated by DNA methylation. There are genetic differences between gut gene expression and the gut microbiota. These findings provide evidence for new therapeutic targets in the future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70027","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T11:53:04Z","timestamp":1734695584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bone morphogenetic proteins, <scp>DNA<\/scp> methylation, and gut microbiota interaction in lumbar disc degeneration: A multi\u2010omics Mendelian randomization study"],"prefix":"10.1002","volume":"7","author":[{"given":"Xiang\u2010Yu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng\u2010Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Zibo Central Hospital  Zibo Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi\u2010Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai\u2010Kang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases  Beijing 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