{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:10:12Z","timestamp":1771927812447,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014761","name":"Qingdao Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["24-4-4-zrjj-113-jch"],"award-info":[{"award-number":["24-4-4-zrjj-113-jch"]}],"id":[{"id":"10.13039\/501100014761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2025QC886"],"award-info":[{"award-number":["ZR2025QC886"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, yet the shared genetic variants underlying these conditions remain poorly understood. This study aimed to investigate shared genetic variants underlying lung function and glucose levels in middle-aged Chinese twins. Methods: In this exploratory analysis, we reanalyzed genotype data from a previously published northern Chinese twin sample, including 139 dizygotic and 238 monozygotic twin pairs from the Qingdao Twin Registry. Lung function traits (FEV1, FVC, and FEV1\/FVC) and fasting plasma glucose (FPG) were jointly analyzed using a twin-based bivariate genome-wide association approach, followed by functional annotation and gene-based analyses. Variants showing suggestive associations were further examined in an independent UK Biobank Chinese sample. Results: A significant negative correlation between the FEV1\/FVC ratio and FPG was revealed. The analysis identified 29 SNPs reaching genome-wide significance, with association signals primarily clustering at the 2q33.1 locus. Functional annotation indicated that most associated variants were non-coding, with several SNPs overlapping regulatory elements annotated to the SPATS2L locus. Gene-based analysis further supported the involvement of SPATS2L in the shared genetic architecture of the two traits. In the validation analysis, seven variants at the 2q33.1 locus showed nominal associations with consistent effect directions. Conclusions: This exploratory bivariate analysis provides evidence supporting shared genetic variants underlying pulmonary function and glucose regulation and offers insight into the genetic basis of COPD\u2013T2DM comorbidity.<\/jats:p>","DOI":"10.3390\/genes17030251","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:54:56Z","timestamp":1771923296000},"page":"251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Bivariate Genome-Wide Analysis in Northern Chinese Twins Suggests Potential Loci at 2q33.1 Harboring SPATS2L for Lung Function and Fasting Plasma Glucose"],"prefix":"10.3390","volume":"17","author":[{"given":"Xinyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, The College of Public Health, Qingdao University, NO. 308 Ning Xia Street, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, The College of Public Health, Qingdao University, NO. 308 Ning Xia Street, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-5414","authenticated-orcid":false,"given":"Chunsheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Qingdao Municipal Center for Disease Control and Prevention, Qingdao 266033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-7649","authenticated-orcid":false,"given":"Weijing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, The College of Public Health, Qingdao University, NO. 308 Ning Xia Street, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaocao","family":"Tian","sequence":"additional","affiliation":[{"name":"Qingdao Municipal Center for Disease Control and Prevention, Qingdao 266033, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-9371","authenticated-orcid":false,"given":"Dongfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, The College of Public Health, Qingdao University, NO. 308 Ning Xia Street, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2346598","DOI":"10.1001\/jamanetworkopen.2023.46598","article-title":"Global Burden of Chronic Obstructive Pulmonary Disease Through 2050","volume":"6","author":"Boers","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_3","first-page":"100937","article-title":"Sociodemographic correlates with prevalence of comorbidities in patients with chronic obstructive pulmonary disease: A study from a Chinese National Survey","volume":"42","author":"Huang","year":"2024","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41533-019-0138-6","article-title":"Incidence of type II diabetes in chronic obstructive pulmonary disease: A nested case-control study","volume":"29","author":"Gayle","year":"2019","journal-title":"NPJ Prim. Care Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.diabres.2009.10.019","article-title":"Comorbidity in the elderly with diabetes: Identification of areas of potential treatment conflicts","volume":"87","author":"Caughey","year":"2010","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.diabres.2018.01.037","article-title":"Population-based cohort study suggesting a significantly increased risk of developing chronic obstructive pulmonary disease in people with type 2 diabetes mellitus","volume":"138","author":"Hsu","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Park, S.S., Perez Perez, J.L., Perez Gandara, B., Agudelo, C.W., Rodriguez Ortega, R., Ahmed, H., Garcia-Arcos, I., McCarthy, C., and Geraghty, P. (2022). Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?. Medicina, 58.","DOI":"10.3390\/medicina58081030"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Anghel, L., Ciubar\u0103, A., Patra\u0219, D., and Ciubar\u0103, A.B. (2025). Chronic Obstructive Pulmonary Disease and Type 2 Diabetes Mellitus: Complex Interactions and Clinical Implications. J. Clin. Med., 14.","DOI":"10.3390\/jcm14061809"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.tips.2017.07.003","article-title":"Targeting Mechanisms Linking COPD to Type 2 Diabetes Mellitus","volume":"38","author":"Cazzola","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jaci.2013.06.018","article-title":"Genome-wide association study of lung function phenotypes in a founder population","volume":"133","author":"Yao","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1017\/thg.2016.97","article-title":"Genetic and Environmental Influences on Pulmonary Function and Muscle Strength: The Chinese Twin Study of Aging","volume":"20","author":"Tian","year":"2017","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.metabol.2009.04.041","article-title":"Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India","volume":"58","author":"Mathias","year":"2009","journal-title":"Metab. Clin. Exp."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, W., Zhang, C., Liu, H., Xu, C., Duan, H., Tian, X., and Zhang, D. (2020). Heritability and genome-wide association analyses of fasting plasma glucose in Chinese adult twins. BMC Genom., 21.","DOI":"10.1186\/s12864-020-06898-z"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.rmed.2015.05.015","article-title":"Comorbidity between chronic obstructive pulmonary disease and type 2 diabetes: A nation-wide cohort twin study","volume":"109","author":"Meteran","year":"2015","journal-title":"Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhu, J., Zhao, H., Chen, D., Tse, L.A., Kinra, S., and Li, Y. (2021). Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.777487"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41588-023-01314-0","article-title":"Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk","volume":"55","author":"Shrine","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/s41588-023-01462-3","article-title":"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification","volume":"55","author":"Lagou","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, L., Pei, Y.F., Li, J., Papasian, C.J., and Deng, H.W. (2009). Univariate\/multivariate genome-wide association scans using data from families and unrelated samples. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006502"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1086\/302038","article-title":"Multiple phenotype modeling in gene-mapping studies of quantitative traits: Power advantages","volume":"63","author":"Allison","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.tics.2021.06.007","article-title":"Twin studies to GWAS: There and back again","volume":"25","author":"Friedman","year":"2021","journal-title":"Trends Cogn. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1017\/thg.2012.113","article-title":"The Qingdao Twin Registry: A status update","volume":"16","author":"Duan","year":"2013","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1017\/thg.2016.98","article-title":"Genetic and Environmental Basis in Phenotype Correlation Between Physical Function and Cognition in Aging Chinese Twins","volume":"20","author":"Xu","year":"2017","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_23","first-page":"1","article-title":"Quality control procedures for genome-wide association studies","volume":"68","author":"Turner","year":"2011","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sharma, J., Jangale, V., Shekhawat, R.S., and Yadav, P. (2025). Improving genetic variant identification for quantitative traits using ensemble learning-based approaches. BMC Genom., 26.","DOI":"10.1186\/s12864-025-11443-x"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/nprot.2015.077","article-title":"Population-specific genotype imputations using minimac or IMPUTE2","volume":"10","author":"Kanterakis","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_26","unstructured":"Neale, M.C., and Maes, H.H. (2004). Methodology for Genetic Studies of Twins and Families, Kluwer Academic Publishers."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/bib\/3.2.119","article-title":"Analytic approaches to twin data using structural equation models","volume":"3","author":"Rijsdijk","year":"2002","journal-title":"Brief. Bioinform."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/BF02294359","article-title":"Factor analysis and AIC","volume":"52","author":"Akaike","year":"1987","journal-title":"Psychometrika"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/ng.2310","article-title":"Genome-wide efficient mixed-model analysis for association studies","volume":"44","author":"Zhou","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: A tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK Biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., and Landray, M. (2015). UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001779"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41588-018-0321-7","article-title":"New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries","volume":"51","author":"Shrine","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41588-023-01372-4","article-title":"Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models","volume":"55","author":"Cosentino","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ajhg.2018.11.008","article-title":"Leveraging Polygenic Functional Enrichment to Improve GWAS Power","volume":"104","author":"Kichaev","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhu, C.H., Kim, J., Shay, J.W., and Wright, W.E. (2008). SGNP: An essential Stress Granule\/Nucleolar Protein potentially involved in 5.8s rRNA processing\/transport. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003716"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1177\/0394632017694625","article-title":"Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis","volume":"30","author":"Lunin","year":"2017","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1080\/08820130802447629","article-title":"Thymulin, a thymic peptide, prevents the overproduction of pro-inflammatory cytokines and heat shock protein Hsp70 in inflammation-bearing mice","volume":"37","author":"Lunin","year":"2008","journal-title":"Immunol. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/toxsci\/kfv084","article-title":"Genome-Wide Association Study Identifies Novel Loci Associated with Diisocyanate-Induced Occupational Asthma","volume":"146","author":"Yucesoy","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Anderson, D., Cordell, H.J., Fakiola, M., Francis, R.W., Syn, G., Scaman, E.S., Davis, E., Miles, S.J., McLeay, T., and Jamieson, S.E. (2015). First genome-wide association study in an Australian aboriginal population provides insights into genetic risk factors for body mass index and type 2 diabetes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119333"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12765","DOI":"10.1111\/ijpo.12765","article-title":"Genome-wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study","volume":"16","author":"Buchanan","year":"2021","journal-title":"Pediatr. Obes."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e143078","DOI":"10.1172\/JCI143078","article-title":"C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation","volume":"131","author":"Lausberg","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zheng, J.S., Arnett, D.K., Lee, Y.C., Shen, J., Parnell, L.D., Smith, C.E., Richardson, K., Li, D., Borecki, I.B., and Ordov\u00e1s, J.M. (2013). Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077442"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106877","DOI":"10.1016\/j.rmed.2022.106877","article-title":"A genome-wide association study on frequent exacerbation of asthma depending on smoking status","volume":"199","author":"Son","year":"2022","journal-title":"Respir. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2337\/db09-0653","article-title":"A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose","volume":"59","author":"Paterson","year":"2010","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Meigs, J.B., Manning, A.K., Fox, C.S., Florez, J.C., Liu, C., Cupples, L.A., and Dupuis, J. (2007). Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med. Genet., 8.","DOI":"10.1186\/1471-2350-8-S1-S16"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wilk, J.B., Walter, R.E., Laramie, J.M., Gottlieb, D.J., and O\u2019Connor, G.T. (2007). Framingham Heart Study genome-wide association: Results for pulmonary function measures. BMC Med. Genet., 8.","DOI":"10.1186\/1471-2350-8-S1-S8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1164\/rccm.201604-0861OC","article-title":"Identification of Four Novel Loci in Asthma in European American and African American Populations","volume":"195","author":"Almoguera","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.2337\/db12-1077","article-title":"Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India","volume":"62","author":"Saxena","year":"2013","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eadt0539","DOI":"10.1126\/sciadv.adt0539","article-title":"Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population","volume":"11","author":"Liu","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s42003-023-04443-8","article-title":"A genome-wide association study identifies distinct variants associated with pulmonary function among European and African ancestries from the UK Biobank","volume":"6","author":"Sinkala","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/s41588-020-0637-y","article-title":"Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis","volume":"52","author":"Vujkovic","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1038\/s41467-025-58248-w","article-title":"A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases","volume":"16","author":"You","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3946320231193832","DOI":"10.1177\/03946320231193832","article-title":"Activation of GPR81 aggravated intestinal ischemia\/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation","volume":"37","author":"Yili","year":"2023","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1053\/j.gastro.2014.03.014","article-title":"Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity","volume":"146","author":"Hoque","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1183\/09031936.00088209","article-title":"Systemic inflammatory markers in COPD: Results from the Bergen COPD Cohort Study","volume":"35","author":"Eagan","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1159\/000210263","article-title":"Role of TNF-\u03b1, sTNF-R55 and sTNF-R75 in inflammation of acute exacerbations of chronic obstructive pulmonary disease","volume":"78","author":"Zeng","year":"2009","journal-title":"Respiration"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ayash, R., Kabalan, Y., and Chamaa, S. (2025). Association of soluble apoptotic biomarkers (FAS, TNFR1 and TRAIL-R2) with \u03b2-cell dysfunction in early glucose dysregulation. BMC Endocr. Disord., 25.","DOI":"10.1186\/s12902-025-02001-3"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41588-024-02044-7","article-title":"A scalable variational inference approach for increased mixed-model association power","volume":"57","author":"Loya","year":"2025","journal-title":"Nat. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jaci.2013.01.051","article-title":"Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients","volume":"132","author":"Li","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-024-07019-6","article-title":"Genetic drivers of heterogeneity in type 2 diabetes pathophysiology","volume":"627","author":"Suzuki","year":"2024","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.metabol.2015.10.001","article-title":"Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2","volume":"65","author":"Graff","year":"2016","journal-title":"Metab. Clin. Exp."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ygcen.2016.08.011","article-title":"Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells","volume":"237","author":"Wang","year":"2016","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7740","DOI":"10.1038\/s41467-023-43622-3","article-title":"Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a","volume":"14","author":"Sun","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1515\/bmc-2018-0008","article-title":"Polymorphisms in DNA repair genes increase the risk for type 2 diabetes mellitus and hypertension","volume":"9","author":"Das","year":"2018","journal-title":"Biomol. Concepts"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1128\/MCB.22.6.1858-1867.2002","article-title":"The Rab27a\/granuphilin complex regulates the exocytosis of insulin-containing dense-core granules","volume":"22","author":"Yi","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1242\/jcs.109.9.2265","article-title":"Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells","volume":"109","author":"Regazzi","year":"1996","journal-title":"J. Cell Sci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/251\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:17:31Z","timestamp":1771924651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/3\/251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":70,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["genes17030251"],"URL":"https:\/\/doi.org\/10.3390\/genes17030251","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]}}}