{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:07:11Z","timestamp":1774008431382,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Valley Baptist Legacy Foundation-supported Project THRIVE"},{"name":"Knapp Community Care Foundation","award":["U54 HG013247"],"award-info":[{"award-number":["U54 HG013247"]}]},{"name":"Knapp Community Care Foundation","award":["R01 MD912564"],"award-info":[{"award-number":["R01 MD912564"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families living in the Rio Grande Valley of south Texas. We collected clinical data, biometric measurements, hepatic health assessments using Vibration-Controlled Transient Elastography (VCTE), and depression evaluations determined with the Beck Depression Inventory-II. We estimated the heritability (h2) of MASLD-related measures, depression status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), the AST\/ALT ratio, and Vibration-Controlled Transient Elastography measurements. For each gene, we derived a genetic endophenotype representing its expression level. We then performed functional network and gene ontology enrichment analyses to characterize the underlying protein pathways. Results: We observed significant associations between the expression of two genes, Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) (h2 = 0.56 [0.45, 0.67]) and ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7) (h2 = 0.66 [0.55, 0.77]), with depression and multiple MASLD-related phenotypes. We identified 351 genes with expression levels significantly correlated with one or more MASLD phenotypes and depression. Among these, five genes\u2014ADAMTS7, THRAP3, CHPM4A, RAB9A, and PDIA3\u2014were jointly associated with three phenotypes: AST\/ALT, ALT, and Controlled Attenuation Parameter (CAP kPa). Based on the Fisher Combined Test, only THRAP3 (p = 3.0 \u00d7 10\u22122) and ADAMTS7 (p = 2 \u00d7 10\u22122) were jointly significant for depression (BDI-II) and AST, ALT, AST\/ALT ratio, FAST, and CAP (kPa). We present a protein\u2013protein interaction network comprising nodes (proteins) and edges (interactions), and a gene ontology enrichment analysis of cellular components. Discussion: Our findings highlight pleiotropic genes underlying MASLD and depression. Two genes, ADAMTS7 and THRAP3, warrant further investigation as potential targets for therapeutic interventions to manage MASLD and depression among Mexican Americans. These results may improve our understanding of the pathways involved in these two diseases, advance current research, and contribute to improvements in personalized medicine. Conclusion: We identified possible shared gene expression phenotypes linking MASLD and depression, which may provide insight into a common molecular underpinning. Pathway enrichment and gene analysis were used to help refine networks and enhance our understanding of complex gene-environmental interactions and their implications for precision medicine.<\/jats:p>","DOI":"10.3390\/genes17030343","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variants and Molecular Components Associated with Metabolic Dysfunctional-Associated Steatotic Liver Disease and Depression: Shared Association of ADAMTS7 and THRAP3"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-1823","authenticated-orcid":false,"given":"Eron G.","family":"Manusov","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"},{"name":"South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3735-6912","authenticated-orcid":false,"given":"Vincent P.","family":"Diego","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"},{"name":"South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-3892","authenticated-orcid":false,"given":"Marcio","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"},{"name":"South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-0474","authenticated-orcid":false,"given":"Jacob A.","family":"Galan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"},{"name":"South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Herklotz","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Edwardo","family":"Abrego III","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habiba","family":"Sultana","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1481-3591","authenticated-orcid":false,"given":"Luis","family":"Pena Marquez","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-560X","authenticated-orcid":false,"given":"Marco A.","family":"Arriaga","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Leandro","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-5579","authenticated-orcid":false,"given":"Juan","family":"Peralta","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"},{"name":"South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX 78520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-3469","authenticated-orcid":false,"given":"Ana","family":"C. 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