{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T05:29:18Z","timestamp":1763098158521,"version":"3.45.0"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":["82173628"],"award-info":[{"award-number":["82173628"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hubei Provincial Natural Science Foundation of China","award":["2024AFB027"],"award-info":[{"award-number":["2024AFB027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Endocrine autoimmune diseases (AIDs) exhibit special polygenic characteristics in human leucocyte antigen (HLA) region. Current understanding of their association with lipid metabolism remains constrained by imprecise polygenic risk score (PRS) modeling. Advanced analytical approaches are needed to elucidate the association between genetic susceptibility and lipid metabolic dysregulation. Methods: We proposed a genetic distance-based clumping gPRS to account for linkage disequilibrium in the HLA region. gPRS and pathway gPRS were constructed for individuals diagnosed with type I diabetes (T1D), Graves\u2019 disease (GD), Hashimoto thyroiditis (HT) and Addison\u2019s disease (AD) in the UK Biobank, with sex considered as a stratification factor. Latent correlations between gPRS and phenotypes were explored using Kendall\u2019s tau test, two-trait LD score regression (LDSC) and gene annotation. Results: Lipid metabolism served an important function through immune and inflammatory biomarkers across multiple traits. Males with low genetic risk tended to have lower high-density lipoprotein cholesterol level, while the correlation presented the opposite pattern in females. Increased genetic susceptibility to AIDs was associated with elevated levels of low-density lipoprotein cholesterol, triglycerides in low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) across all traits. Moreover, levels of polyunsaturated fatty acids, including omega-3 and omega-6, decreased with higher PRS in males and females, while those of monounsaturated fatty acids exhibited an increasing trend. Conclusion: Our study constructed more precise polygenic risk scores of AIDs, highlighting inflammation-mediated lipid metabolism as a potential pathogenic mechanism in endocrine AIDs, offering valuable insights into shared etiology for future comprehensive investigations.<\/jats:p>","DOI":"10.3390\/genes16111379","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"1379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation-Mediated Lipid Metabolism in Endocrine Autoimmune Diseases: A Genetic Distance-Based PRS Approach Integrating HLA Region"],"prefix":"10.3390","volume":"16","author":[{"given":"Fenghuixue","family":"Liu","sequence":"first","affiliation":[{"name":"School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1515\/cclm-2017-1108","article-title":"The Natural History of Autoimmune Addison\u2019s Disease with a Non-Classical Presentation: A Case Report and Review of Literature","volume":"56","author":"Manso","year":"2018","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/MED.0000000000000790","article-title":"Lipid-Lowering Therapies and Cardiovascular Risk-Stratification Strategies in Adults with Type 1 Diabetes","volume":"30","author":"Lan","year":"2023","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1097\/IOP.0000000000002525","article-title":"Statins in Graves Orbitopathy: A New Therapeutic Tool","volume":"39","author":"Lanzolla","year":"2023","journal-title":"Ophthal. Plast. Reconstr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1507\/endocrj.K09E-315","article-title":"Lipid Profiles in the Untreated Patients with Hashimoto Thyroiditis and the Effects of Thyroxine Treatment on Subclinical Hypothyroidism with Hashimoto Thyroiditis","volume":"57","author":"Tagami","year":"2010","journal-title":"Endocr. J."},{"key":"ref_5","first-page":"e13364","article-title":"Addison\u2019s Disease: A Diagnosis Easy to Overlook","volume":"13","author":"Mosca","year":"2021","journal-title":"Cureus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1194\/jlr.R066514","article-title":"Lipid Signaling and Lipotoxicity in Metaflammation: Indications for Metabolic Disease Pathogenesis and Treatment","volume":"57","author":"Ertunc","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41589-022-01017-3","article-title":"Lipid Metabolism in T Cell Signaling and Function","volume":"18","author":"Lim","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13045-021-01200-4","article-title":"Contradictory Roles of Lipid Metabolism in Immune Response within the Tumor Microenvironment","volume":"14","author":"Yu","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e138034","DOI":"10.1172\/jci.insight.138034","article-title":"Lipid Mediators and Biomarkers Associated with Type 1 Diabetes Development","volume":"5","author":"Nelson","year":"2020","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10709-021-00138-2","article-title":"Associating Complex Traits with Genetic Variants: Polygenic Risk Scores, Pleiotropy and Endophenotypes","volume":"150","author":"Fisch","year":"2022","journal-title":"Genetica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1001\/jamapsychiatry.2020.3049","article-title":"From Basic Science to Clinical Application of Polygenic Risk Scores: A Primer","volume":"78","author":"Wray","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/joim.12395","article-title":"Human Autoimmune Diseases: A Comprehensive Update","volume":"278","author":"Wang","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1608","DOI":"10.1002\/mpr.1608","article-title":"A Tutorial on Conducting Genome-Wide Association Studies: Quality Control and Statistical Analysis","volume":"27","author":"Marees","year":"2018","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ajhg.2008.06.005","article-title":"Long-Range LD Can Confound Genome Scans in Admixed Populations","volume":"83","author":"Price","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mastana, S., Knight, E., Hampson, A., Akam, L., Hunter, D.J., Ghelani, A., Samanta, A., and Singh, P. (2024). Role of Selected Genetic Polymorphisms in the Development of Rheumatoid Arthritis in a British White Population. Genes, 15.","DOI":"10.3390\/genes15081009"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1038\/s41467-019-09718-5","article-title":"Polygenic Prediction via Bayesian Regression and Continuous Shrinkage Priors","volume":"10","author":"Ge","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1093\/bioinformatics\/btaa1029","article-title":"LDpred2: Better, Faster, Stronger","volume":"36","author":"Arbel","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2106858119","DOI":"10.1073\/pnas.2106858119","article-title":"Mendelian Randomization for Causal Inference Accounting for Pleiotropy and Sample Structure Using Genome-Wide Summary Statistics","volume":"119","author":"Hu","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.3211","article-title":"LD Score Regression Distinguishes Confounding from Polygenicity in Genome-Wide Association Studies","volume":"47","author":"Loh","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1056\/NEJMoa1502214","article-title":"FTO Obesity Variant Circuitry and Adipocyte Browning in Humans","volume":"373","author":"Claussnitzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1111\/dom.14777","article-title":"The Missing Heritability in Type 1 Diabetes","volume":"24","author":"Pang","year":"2022","journal-title":"Diabetes Obes. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tywanek, E., Michalak, A., \u015awirska, J., and Zwolak, A. (2024). Autoimmunity, New Potential Biomarkers and the Thyroid Gland\u2014The Perspective of Hashimoto\u2019s Thyroiditis and Its Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094703"},{"key":"ref_23","first-page":"367","article-title":"Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1. Ann","volume":"35","author":"Koyama","year":"2023","journal-title":"Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s43587-021-00051-5","article-title":"Common Genetic Associations between Age-Related Diseases","volume":"1","author":"Fabian","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2117523119","DOI":"10.1073\/pnas.2117523119","article-title":"Up-Regulation of BTN3A1 on CD14+ Cells Promotes V\u03b39V\u03b42 T Cell Activation in Psoriasis","volume":"119","author":"Zhou","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/s41586-023-06525-3","article-title":"Phosphoantigens Glue Butyrophilin 3A1 and 2A1 to Activate V\u03b39V\u03b42 T Cells","volume":"621","author":"Yuan","year":"2023","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1186\/s12967-023-04514-8","article-title":"B7H3-Targeting Chimeric Antigen Receptor Modification Enhances Antitumor Effect of V\u03b39V\u03b42 T Cells in Glioblastoma","volume":"21","author":"Wang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12289","DOI":"10.1080\/21655979.2022.2070965","article-title":"Long Non-Coding RNA HLA-F Antisense RNA 1 Inhibits the Maturation of microRNA-613 in Polycystic Ovary Syndrome to Promote Ovarian Granulosa Cell Proliferation and Inhibit Cell Apoptosis","volume":"13","author":"Li","year":"2022","journal-title":"Bioengineered"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, C.-H., Liu, X.-Y., and Wang, J. (2023). Essential Role of Granulosa Cell Glucose and Lipid Metabolism on Oocytes and the Potential Metabolic Imbalance in Polycystic Ovary Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216247"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pu, Y., Zhao, H., Wu, X., Mei, M., and Shen, B. (2020). The Long Noncoding RNA Ptprd-IR Is a Novel Molecular Target for TGF-\u03921-Mediated Nephritis. Int. J. Biochem. Cell Biol., 122.","DOI":"10.1016\/j.biocel.2020.105742"},{"key":"ref_31","unstructured":"Nagesh, P.T., Nishi, H., Rawal, S., Zahr, T., Miano, J.M., Sorci-Thomas, M., Xu, H., Akbar, N., Choudhury, R.P., and Misra, A. (2023). HDL Regulates TGF\u00df-Receptor Lipid Raft Partitioning, Restoring Contractile Features of Cholesterol-Loaded Vascular Smooth Muscle Cells. bioRxiv."},{"key":"ref_32","first-page":"6288","article-title":"LncRNA HULC Alleviates HUVEC Inflammation and Improves Angiogenesis after Myocardial Infarction through Down-Regulating miR-29b","volume":"24","author":"Chen","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/jcmm.12956","article-title":"HULC: An Oncogenic Long Non-Coding RNA in Human Cancer","volume":"21","author":"Yu","year":"2017","journal-title":"J. Cell Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1186\/s13018-023-04003-0","article-title":"Down-Regulation of Long Noncoding RNA HULC Inhibits the Inflammatory Response in Ankylosing Spondylitis by Reducing miR-556-5p-Mediated YAP1 Expression","volume":"18","author":"Yi","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1186\/s40001-023-01468-x","article-title":"Grid2 Interacting Protein Is a Potential Biomarker Related to Immune Infiltration in Colorectal Cancer","volume":"28","author":"Zhao","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_36","unstructured":"Comparative Genetic Architectures of Schizophrenia in East Asian and European Populations.\u2014Abstract\u2014Europe PMC. Available online: https:\/\/europepmc.org\/article\/med\/31740837."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Panyard, D.J., Kim, K.M., Darst, B.F., Deming, Y.K., Zhong, X., Wu, Y., Kang, H., Carlsson, C.M., Johnson, S.C., and Asthana, S. (2021). Cerebrospinal Fluid Metabolomics Identifies 19 Brain-Related Phenotype Associations. Commun. Biol., 4.","DOI":"10.1038\/s42003-020-01583-z"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13046-024-03019-6","article-title":"Tumor Suppressor Role of the Complement Inhibitor CSMD1 and Its Role in TNF-Induced Neuroinflammation in Gliomas","volume":"43","author":"Tuysuz","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wang, Z., Li, M., Sun, P., Bai, T., Wang, W., Bai, H., Gou, J., and Wang, Z. (2021). HCG18 Participates in Vascular Invasion of Hepatocellular Carcinoma by Regulating Macrophages and Tumor Stem Cells. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.707073"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4747","DOI":"10.2147\/DMSO.S333431","article-title":"Upregulated lncRNA HCG18 in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance","volume":"14","author":"Xia","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Noble, J.A. (2024). Fifty Years of HLA-Associated Type 1 Diabetes Risk: History, Current Knowledge, and Future Directions. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457213"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Stasiak, M., Zawadzka-Starczewska, K., Tymoniuk, B., Stasiak, B., and Lewi\u0144ski, A. (2023). Associations between Lipid Profiles and Graves\u2019 Orbitopathy Can Be HLA-Dependent. Genes, 14.","DOI":"10.3389\/fimmu.2023.1256922"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chiorean, A.-D., Nicula, G.Z., B\u00e2lici, \u0218., Vic\u0103, M.L., Iancu Loga, L.-I., Dican, L., and Matei, H.V. (2024). HLA Class II Allele Groups Involved in Autoimmune Thyroid Diseases: Hashimoto\u2019s Thyroiditis and Basedow\u2013Graves Disease. Life, 14.","DOI":"10.3390\/life14040441"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1156409","article-title":"Genetic Mapping in Human Disease","volume":"322","author":"Altshuler","year":"2008","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","article-title":"An Open Approach to Systematically Prioritize Causal Variants and Genes at All Published Human GWAS Trait-Associated Loci","volume":"53","author":"Mountjoy","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2020.07.019","article-title":"Lipoproteins and Lipids in Cardiovascular Disease: From Mechanistic Insights to Therapeutic Targeting","volume":"159","author":"Soppert","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yang, H.S., Jeong, H.J., Kim, H., Lee, S., and Hur, M. (2023). Sex-Specific Relationships between HDL-Cholesterol Levels and 10-Year Mortality in Individuals with Atherosclerotic Cardiovascular Disease: A Nationwide Cohort Study of South Koreans. Metabolites, 13.","DOI":"10.20944\/preprints202311.0373.v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/immu.200390020","article-title":"Characterization of HLA DR3\/DQ2 Transgenic Mice: A Potential Humanized Animal Model for Autoimmune Disease Studies","volume":"33","author":"Chen","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"bqae148","DOI":"10.1210\/endocr\/bqae148","article-title":"Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility","volume":"165","author":"Simizo","year":"2024","journal-title":"Endocrinology"},{"key":"ref_50","first-page":"125","article-title":"Remnant Cholesterol and Low-Grade Inflammation Jointly in Atherosclerotic Cardiovascular Disease: Implications for Clinical Trials","volume":"27","author":"Doi","year":"2024","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Prasun, P. (2020). Mitochondrial Dysfunction in Metabolic Syndrome. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165838"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wu, Y., Huang, M., Chen, X., Wu, J., Li, L., Wei, J., Lu, C., Han, L., and Lu, Y. (2024). A Genome-Wide Cross-Trait Analysis Identifies Shared Loci and Causal Relationships of Obesity and Lipidemic Traits with Psoriasis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1328297"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmet.2018.05.008","article-title":"Sex Differences in Lipid and Lipoprotein Metabolism","volume":"15","author":"Palmisano","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Coniglio, S., Shumskaya, M., and Vassiliou, E. (2023). Unsaturated Fatty Acids and Their Immunomodulatory Properties. Biology, 12.","DOI":"10.3390\/biology12020279"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ravaut, G., L\u00e9giot, A., Bergeron, K.-F., and Mounier, C. (2021). Monounsaturated Fatty Acids in Obesity-Related Inflammation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010330"},{"key":"ref_56","first-page":"755","article-title":"Potential Contribution of Monounsaturated Fatty Acids to Cardiovascular Risk in Chronic Kidney Disease","volume":"128","author":"Mika","year":"2018","journal-title":"Pol. Arch. Intern. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T05:28:36Z","timestamp":1763098116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/11\/1379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["genes16111379"],"URL":"https:\/\/doi.org\/10.3390\/genes16111379","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,11,12]]}}}