{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:26:35Z","timestamp":1787199995854,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82473644"],"award-info":[{"award-number":["82473644"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404362"],"award-info":[{"award-number":["82404362"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82073653"],"award-info":[{"award-number":["82073653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82473644"],"award-info":[{"award-number":["82473644"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82404362"],"award-info":[{"award-number":["82404362"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82073653"],"award-info":[{"award-number":["82073653"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hunan Outstanding Youth Fund Project","award":["2022JJ10087"],"award-info":[{"award-number":["2022JJ10087"]}]},{"name":"Hunan Provincial Science and Technology Talent Support Project","award":["2020TJ-N07"],"award-info":[{"award-number":["2020TJ-N07"]}]},{"name":"Hunan Provincial Key Research and Development Program","award":["2018SK2063"],"award-info":[{"award-number":["2018SK2063"]}]},{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hunan Province of China","doi-asserted-by":"crossref","award":["2022JJ40207"],"award-info":[{"award-number":["2022JJ40207"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Changsha Municipal Natural Science Foundation","award":["kq2202470"],"award-info":[{"award-number":["kq2202470"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Intervertebral disc degeneration (IDD) is a multifactorial spinal degenerative condition influenced by inherited susceptibility and environmental exposures. Genetic evidence from Chinese Han populations remains limited. This study aimed to evaluate GWAS-informed and previously reported candidate single-nucleotide polymorphisms (SNPs) associated with IDD and to explore potential gene\u2013gene and gene\u2013environment interaction patterns. Methods: A hospital-based case\u2013control study was conducted in 1951 unrelated Chinese Han participants, including 929 patients with magnetic resonance imaging-confirmed IDD and 1022 control subjects without evident IDD. Candidate SNPs were genotyped using the MassARRAY platform. Multivariable logistic regression was used to assess genetic associations under different genetic models, and linkage disequilibrium, haplotype associations, additive and multiplicative interactions, and generalized multifactor dimensionality reduction (GMDR) were further evaluated. Results: Of the 60 initially selected candidate SNPs, 49 passed quality control and were retained for association analyses. Several variants showed nominal associations with IDD susceptibility. Representative associations included MMP3 rs591058 under the recessive model (OR = 1.37, 95% CI: 1.06\u20131.79, p = 0.019) and VDR rs2228570 under the dominant model (OR = 1.52, 95% CI: 1.10\u20132.11, p = 0.012), whereas the CCDC26 rs6651255\u2013rs7816342 AC haplotype showed a protective association (OR = 0.87, 95% CI: 0.76\u20130.99, p = 0.046). Exploratory interaction analyses suggested possible gene\u2013gene interactions involving ACAN, IL1B, VDR, CASP3, and CEP162\/RIPPLY2, as well as gene\u2013environment interactions involving smoking, weight-bearing workload, and duration of bending work. Conclusions: This study provides preliminary genetic epidemiological evidence that GWAS-informed candidate variants and exploratory interaction patterns may be associated with IDD susceptibility in the Chinese Han population. These findings require further replication and functional validation.<\/jats:p>","DOI":"10.3390\/genes17080967","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:12:11Z","timestamp":1787069531000},"page":"967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GWAS-Informed Candidate Genetic Variants and Gene\u2013Gene\/Gene\u2013Environment Interaction Patterns Associated with Intervertebral Disc Degeneration: A Chinese Han Case\u2013Control Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Ridan","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9360-4991","authenticated-orcid":false,"given":"Jiabi","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1097\/01.brs.0000231761.73859.2c","article-title":"What is intervertebral disc degeneration, and what causes it?","volume":"31","author":"Adams","year":"2006","journal-title":"Spine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1093\/neuros\/nyw078","article-title":"Intervertebral disk degeneration and repair","volume":"80","author":"Dowdell","year":"2017","journal-title":"Neurosurgery"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.joca.2015.03.028","article-title":"Mechanics and biology in intervertebral disc degeneration: A vicious circle","volume":"23","author":"Vergroesen","year":"2015","journal-title":"Osteoarthr. 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