{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:02:56Z","timestamp":1789981376371,"version":"4.0.1"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Appendicular lean mass (ALM), alanine aminotransferase (ALT), and type 2 diabetes (T2D) may be genetically linked. However, the ALT-related pathway and shared signals at the SERPINA1 candidate locus remain uncertain. We used Mendelian randomization (MR) to evaluate associations among ALM, ALT, and T2D and compared candidate-locus signals across datasets. ALM represented muscle mass, not clinical sarcopenia. Methods: Using European-ancestry GWAS summary statistics, we performed six bidirectional two-sample MR analyses, multivariable MR (MVMR) with finite-sample t-based inference, and exploratory path-specific two-step MR. FinnGen R12 provided the T2D outcome data for MR and pathway analyses. Pathway analyses used 5000 shared-sampling bootstrap replicates to assess uncertainty in path estimates. We combined locus-level coloc\/ABF with signal-specific SuSiE-coloc in the GRCh37 SERPINA1 region. T2DGGI was used only for colocalization. Molecular-QTL and external-omics analyses were treated as supportive or limiting evidence. Results: Higher genetically predicted ALM was associated with lower ALT and lower T2D risk, whereas higher genetically predicted ALT was associated with greater T2D risk. T2D\u2192ALT was method-dependent. In MVMR, the ALT conditional effect remained positive, whereas the ALM direct effect was model-dependent. Path decomposition was compatible with an ALT-related statistical pathway, but product- and difference-based estimates disagreed, and residual heterogeneity remained. ALM\u2013T2DGGI supported an rs28929474-related shared component, although component-cohort overlap was possible. FinnGen supported other ALT-related signals but did not independently corroborate rs28929474. Tissue eQTL and external omics did not provide consistent mechanistic support. Conclusions: The data support directionally connected MR-based associations and dataset-dependent shared candidate signals. These findings do not establish biological mediation, a unique causal variant, gene-level causal assignment, or a molecular mechanism.<\/jats:p>","DOI":"10.3390\/genes17091154","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Associations Among Appendicular Lean Mass, Alanine Aminotransferase, and Type 2 Diabetes: Multi-Dataset Mendelian Randomization and Colocalization at the SERPINA1 Candidate Locus"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5856-5428","authenticated-orcid":false,"given":"Xinyuan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Physical Education, Yunnan Normal University, 768 Juxian Street, Chenggong District, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Wenchuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Physical Education, Yunnan Normal University, 768 Juxian Street, Chenggong District, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Shuhua","family":"Song","sequence":"additional","affiliation":[{"name":"School of Physical Education, Yunnan Normal University, 768 Juxian Street, Chenggong District, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Huaiyi","family":"Su","sequence":"additional","affiliation":[{"name":"School of Physical Education, Yunnan Normal University, 768 Juxian Street, Chenggong District, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Physical Education, Yunnan Normal University, 768 Juxian Street, Chenggong District, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","article-title":"Sarcopenia","volume":"393","author":"Sayer","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12603-019-1267-x","article-title":"Differences in the Prevalence of Sarcopenia in Community-Dwelling, Nursing Home and Hospitalized Individuals. A Systematic Review and Meta-Analysis","volume":"24","author":"Papadopoulou","year":"2020","journal-title":"J. Nutr. Health Aging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1002\/jcsm.12993","article-title":"Gender Differences in Risk Factors for the 2 Year Development of Sarcopenia in Community-Dwelling Older Adults","volume":"13","author":"Choe","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European Consensus on Definition and Diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/j.2040-4603.2020.tb00136.x","article-title":"Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake","volume":"10","author":"Merz","year":"2020","journal-title":"Compr. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes","volume":"32","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2147\/DMSO.S186600","article-title":"Sarcopenia and Type 2 Diabetes Mellitus: A Bidirectional Relationship","volume":"12","author":"Mesinovic","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13098-021-00707-7","article-title":"The Prevalence and Risk Factors of Sarcopenia in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"13","author":"Ai","year":"2021","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hong, S., Chang, Y., Jung, H.-S., Yun, K.E., Shin, H., and Ryu, S. (2017). Relative Muscle Mass and the Risk of Incident Type 2 Diabetes: A Cohort Study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188650"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/j.mayocp.2022.02.028","article-title":"Association of Self-Reported Walking Pace with Type 2 Diabetes Incidence in the UK Biobank Prospective Cohort Study","volume":"97","author":"Boonpor","year":"2022","journal-title":"Mayo Clin. Proc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1111\/sms.14197","article-title":"Combined Association of Walking Pace and Grip Strength with Incident Type 2 Diabetes","volume":"32","author":"Boonpor","year":"2022","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S2213-8587(14)70034-8","article-title":"Age-Related and Disease-Related Muscle Loss: The Effect of Diabetes, Obesity, and Other Diseases","volume":"2","author":"Kalyani","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Epic-InterAct Consortium, Burgess, S., Scott, R.A., Timpson, N.J., Davey Smith, G., and Thompson, S.G. (2015). Using Published Data in Mendelian Randomization: A Blueprint for Efficient Identification of Causal Risk Factors. Eur. J. Epidemiol., 30, 543\u2013552.","DOI":"10.1007\/s10654-015-0011-z"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian Randomisation Studies: A Guide, Glossary, and Checklist for Clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base Platform Supports Systematic Causal Inference across the Human Phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_16","unstructured":"Terjung, R. (2014). Energy Metabolism in the Liver. Comprehensive Physiology, Wiley."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/s00125-016-3940-5","article-title":"Hepatic Glucose and Lipid Metabolism","volume":"59","author":"Jones","year":"2016","journal-title":"Diabetologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/dmrr.666","article-title":"Alanine Aminotransferase as a Marker of Non-Alcoholic Fatty Liver Disease in Relation to Type 2 Diabetes Mellitus and Cardiovascular Disease","volume":"22","author":"Schindhelm","year":"2006","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.2337\/db18-1048","article-title":"Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study","volume":"68","author":"Borges","year":"2019","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abbasi, A., Bakker, S.J.L., Corpeleijn, E., Van Der A, D.L., Gansevoort, R.T., Gans, R.O.B., Peelen, L.M., Van Der Schouw, Y.T., Stolk, R.P., and Navis, G. (2012). Liver Function Tests and Risk Prediction of Incident Type 2 Diabetes: Evaluation in Two Independent Cohorts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051496"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40842-026-00285-5","article-title":"Sex-Specific Roles of Insulin-like Growth Factor-1, Lean Mass and Fat Mass in Type 2 Diabetes Prevention: Mendelian Randomization Studies in Western and East Asian Populations","volume":"12","author":"Kwok","year":"2026","journal-title":"Cardiovasc. Diabetol. Endocrinol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/hep4.1718","article-title":"Heterozygosity of the Alpha 1-Antitrypsin pi*Z Allele and Risk of Liver Disease","volume":"5","author":"Hakim","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1038\/s41467-022-30931-2","article-title":"Inherited Basis of Visceral, Abdominal Subcutaneous and Gluteofemoral Fat Depots","volume":"13","author":"Agrawal","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100984","DOI":"10.1016\/j.molmet.2020.100984","article-title":"Alpha1-Antitrypsin Ameliorates Islet Amyloid-Induced Glucose Intolerance and \u03b2-Cell Dysfunction","volume":"37","author":"Obach","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., and Plagnol, V. (2014). Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004383"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wallace, C. (2021). A More Accurate Method for Colocalisation Analysis Allowing for Multiple Causal Variants. PLoS Genet., 17.","DOI":"10.1101\/2021.02.23.432421"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s42003-020-01334-0","article-title":"The Genetic Architecture of Appendicular Lean Mass Characterized by Association Analysis in the UK Biobank Study","volume":"3","author":"Pei","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, S., Yan, S., Aiheti, N., Kuribanjiang, K., Yao, X., Wang, Q., Zhou, T., and Yang, L. (2023). A Bi-Directional Mendelian Randomization Study of Sarcopenia-Related Traits and Type 2 Diabetes Mellitus. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1109800"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00125-019-4826-0","article-title":"Lean Mass, Grip Strength and Risk of Type 2 Diabetes: A Bi-Directional Mendelian Randomisation Study","volume":"62","author":"Yeung","year":"2019","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e13923","DOI":"10.1111\/acel.13923","article-title":"Causal Associations of Sarcopenia-Related Traits with Cardiometabolic Disease and Alzheimer\u2019s Disease and the Mediating Role of Insulin Resistance: A Mendelian Randomization Study","volume":"22","author":"Ye","year":"2023","journal-title":"Aging Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen Provides Genetic Insights from a Well-Phenotyped Isolated Population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eadj1182","DOI":"10.1126\/science.adj1182","article-title":"Diversity and Scale: Genetic Architecture of 2068 Traits in the VA Million Veteran Program","volume":"385","author":"Verma","year":"2024","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","article-title":"Meta-Analysis of Genome-Wide Association Studies for Height and Body Mass Index in \u223c700000 Individuals of European Ancestry","volume":"27","author":"Yengo","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-Generation PLINK: Rising to the Challenge of Larger and Richer Datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"1000 Genomes Project Consortium, Abecasis, G.R., Auton, A., Steering Committee, Altshuler, D.M., Durbin, R.M., Abecasis, G.R., Bentley, D.R., Chakravarti, A., and Clark, A.G. (2015). A Global Reference for Human Genetic Variation. Nature, 526, 68\u201374.","DOI":"10.1038\/nature15393"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1214\/19-AOS1866","article-title":"Statistical Inference in Two-Sample Summary-Data Mendelian Randomization Using Robust Adjusted Profile Score","volume":"48","author":"Zhao","year":"2020","journal-title":"Ann. Stat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of Widespread Horizontal Pleiotropy in Causal Relationships Inferred from Mendelian Randomization between Complex Traits and Diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ije\/dyy258","article-title":"Improving the Accuracy of Two-Sample Summary-Data Mendelian Randomization: Moving beyond the NOME Assumption","volume":"48","author":"Bowden","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1093\/ije\/dyy101","article-title":"Improving the Visualization, Interpretation and Analysis of Two-Sample Summary Data Mendelian Randomization via the Radial Plot and Radial Regression","volume":"47","author":"Bowden","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Spiller, W., Bowden, J., and Sanderson, E. (2024). Estimating and Visualising Multivariable Mendelian Randomization Analyses within a Radial Framework. PLoS Genet., 20.","DOI":"10.1371\/journal.pgen.1011506"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1002\/sim.9133","article-title":"Testing and Correcting for Weak and Pleiotropic Instruments in Two-Sample Multivariable Mendelian Randomization","volume":"40","author":"Sanderson","year":"2021","journal-title":"Stat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1002\/sim.7492","article-title":"Extending the MR-Egger Method for Multivariable Mendelian Randomization to Correct for Both Measured and Unmeasured Pleiotropy","volume":"36","author":"Rees","year":"2017","journal-title":"Stat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5813","DOI":"10.1002\/sim.9156","article-title":"Pleiotropy Robust Methods for Multivariable Mendelian Randomization","volume":"40","author":"Grant","year":"2021","journal-title":"Stat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.ajhg.2023.02.014","article-title":"Robust Multivariable Mendelian Randomization Based on Constrained Maximum Likelihood","volume":"110","author":"Lin","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10654-021-00757-1","article-title":"Mendelian Randomisation for Mediation Analysis: Current Methods and Challenges for Implementation","volume":"36","author":"Carter","year":"2021","journal-title":"Eur. J. Epidemiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e10317","DOI":"10.1002\/sim.10317","article-title":"Causal Mediation Analysis: A Summary-Data Mendelian Randomization Approach","volume":"44","author":"Lin","year":"2025","journal-title":"Stat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1111\/rssb.12388","article-title":"A Simple New Approach to Variable Selection in Regression, with Application to Genetic Fine Mapping","volume":"82","author":"Wang","year":"2020","journal-title":"J. R. Stat. Soc. B"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zou, Y., Carbonetto, P., Wang, G., and Stephens, M. (2022). Fine-Mapping from Summary Data with the \u201cSum of Single Effects\u201d Model. PLoS Genet., 18.","DOI":"10.1371\/journal.pgen.1010299"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/s41588-021-00924-w","article-title":"A Compendium of Uniformly Processed Human Gene Expression and Splicing Quantitative Trait Loci","volume":"53","author":"Kerimov","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"GTEx Consortium (2020). The GTEx Consortium Atlas of Genetic Regulatory Effects across Human Tissues. Science, 369, 1318\u20131330.","DOI":"10.1126\/science.aaz1776"},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"5808","DOI":"10.1038\/s41467-019-13694-1","article-title":"Mitochondrial Oxidative Capacity and NAD+ Biosynthesis Are Reduced in Human Sarcopenia across Ethnicities","volume":"10","author":"Migliavacca","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cmet.2013.07.004","article-title":"DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery","volume":"18","author":"Ahrens","year":"2013","journal-title":"Cell Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/gm130","article-title":"Integration of microRNA Changes in Vivo Identifies Novel Molecular Features of Muscle Insulin Resistance in Type 2 Diabetes","volume":"2","author":"Gallagher","year":"2010","journal-title":"Genome Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1093\/nar\/gni179","article-title":"Evolving Gene\/Transcript Definitions Significantly Alter the Interpretation of GeneChip Data","volume":"33","author":"Dai","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"The Gene Ontology Consortium, Carbon, S., Douglass, E., Good, B.M., Unni, D.R., Harris, N.L., Mungall, C.J., Basu, S., Chisholm, R.L., and Dodson, R.J. (2021). The Gene Ontology Resource: Enriching a GOld Mine. Nucleic Acids Res., 49, D325\u2013D334.","DOI":"10.1093\/nar\/gkaa1113"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"D731","DOI":"10.1093\/nar\/gkae1113","article-title":"The STRING Database in 2025: Protein Networks with Directionality of Regulation","volume":"53","author":"Szklarczyk","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4093\/dmj.2023.0112","article-title":"Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies","volume":"47","author":"Mesinovic","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Liu, J., Au Yeung, S.L., Kwok, M.K., Leung, J.Y.Y., Hui, L.L., Leung, G.M., and Schooling, C.M. (2020). The Effect of Liver Enzymes on Body Composition: A Mendelian Randomization Study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228737"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ajg.2016.517","article-title":"ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries","volume":"112","author":"Kwo","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of Hepatic Glucose Metabolism in Health and Disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15674","DOI":"10.1074\/jbc.M116.727826","article-title":"Molecular Mechanism of Z A1-Antitrypsin Deficiency","volume":"291","author":"Huang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1136\/gutjnl-2018-316228","article-title":"Heterozygous Carriage of the Alpha1-Antitrypsin pi*Z Variant Increases the Risk to Develop Liver Cirrhosis","volume":"68","author":"Strnad","year":"2019","journal-title":"Gut"},{"key":"ref_71","first-page":"3941","article-title":"Clathrin-Mediated Endocytosis of Alpha-1 Antitrypsin Is Essential for Its Protective Function in Islet Cell Survival","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s13410-021-00984-y","article-title":"Genetic Polymorphisms in ABCA1 (Rs2230806 and Rs1800977) and LIPC (Rs2070895) Genes and Their Association with the Risk of Type 2 Diabetes: A Case Control Study","volume":"42","author":"Singh","year":"2022","journal-title":"Int. J. Diabetes Dev. Ctries."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100929","DOI":"10.1016\/j.mgene.2021.100929","article-title":"Associations of INPPL1 (+1893CC\/AA and + 2945AA\/GG) Exonic Polymorphisms with the Risk of Type 2 Diabetes Mellitus in North Indian Population: A Case Control Study","volume":"29","author":"Singh","year":"2021","journal-title":"Meta Gene"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: Guaranteeing Well-Connected Communities","volume":"9","author":"Traag","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:26:30Z","timestamp":1789979190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":74,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091154"],"URL":"https:\/\/doi.org\/10.3390\/genes17091154","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}