{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:32:39Z","timestamp":1786523559554,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wenzhou-Kean University Faculty Start-Up Research Grant"},{"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics","award":["WB20211227000125"],"award-info":[{"award-number":["WB20211227000125"]}]},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center at Wenzhou-Kean University","award":["WB20210429000008"],"award-info":[{"award-number":["WB20210429000008"]}]},{"award":["WB20210429000008"],"award-info":[{"award-number":["WB20210429000008"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Genome-wide association studies have identified numerous genetic variants statistically significantly associated with body mass index (BMI). However, the functional mechanisms underlying most associations between single nucleotide polymorphisms (SNPs) in non-coding regions and BMI remain poorly understood. Here, we implemented an integrative 7-criterion quantitative scoring system (gene localization, histone modifications, transcription factor binding sites (TFBS), SNP clouds, tissue expression patterns, evolutionary conservation, and COVID-19 associations) to prioritize putative functional loci among 94 BMI-associated SNPs. Six SNPs resided within long non-coding RNA (lncRNA) genes: rs2245368 (exonic, DTX2P1-UPK3BP1-PMS2P11), rs2033529 (exonic, LINC00951), rs2836754 (intronic, ETS2-AS1), rs2815752 (intronic, LINC02796), rs17203016 (intronic, MYOSLID-AS1), and rs7239883 (intronic, LINC00907). We prioritized them because they are located within lncRNA gene bodies and therefore showed stronger functional support compared to other variants which only had non-coding regulatory elements in their vicinity. Notably, rs1928295 exhibited strong GATA2 binding evidence, while rs13201877 had extensive transcription factor occupancy (64 factors). Multiple variants demonstrated putative regulatory potential through epigenomic evidence, including DNase I hypersensitivity and cell-type-specific chromatin accessibility. We show that most BMI risk alleles are not human-specific and are conserved across primates. Our findings suggest putative candidate non-coding regulatory elements in BMI and provide prioritized obesity-associated non-coding variants for functional validations.<\/jats:p>","DOI":"10.3390\/ijms27157015","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:08:09Z","timestamp":1785856089000},"page":"7015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Annotation of GWAS Loci Using Public Transcriptome and Epigenome Datasets Reveals Non-Coding Genes and Regulatory Elements Which May Contribute to BMI"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4354-9882","authenticated-orcid":false,"given":"Chunting","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7872-4067","authenticated-orcid":false,"given":"Xiangyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biology, New College, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8565-207X","authenticated-orcid":false,"given":"Erica L.","family":"Kleinbrink","sequence":"additional","affiliation":[{"name":"Quantitative Life Sciences, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"King","sequence":"additional","affiliation":[{"name":"College of Arts & Sciences, American University of Iraq, Baghdad, Airport Road, Baghdad 10023, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Lipovich","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou 325035, China"},{"name":"Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"Maurano","year":"2012","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gregory, T.R. (2005). CHAPTER 1\u2014Genome Size Evolution in Animals. The Evolution of the Genome, Academic Press.","DOI":"10.1016\/B978-012301463-4\/50001-2"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shkurat, T.P., Ammar, M., Bocharova, O., Teplyakova, E., Aleksandrova, A., Ali, R., and Lipovich, L. (2023). The Role of Genetic Variants in the Long Non-Coding RNA Genes MALAT1 and H19 in the Pathogenesis of Childhood Obesity. Noncoding RNA, 9.","DOI":"10.3390\/ncrna9020022"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41576-020-0268-2","article-title":"Genetics meets proteomics: Perspectives for large population-based studies","volume":"22","author":"Suhre","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eadh7699","DOI":"10.1126\/science.adh7699","article-title":"Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens","volume":"380","author":"Morris","year":"2023","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s43586-021-00056-9","article-title":"Genome-wide association studies","volume":"1","author":"Uffelmann","year":"2021","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9511","DOI":"10.1002\/cam4.3546","article-title":"An in silico approach to identify and prioritize miRNAs target sites polymorphisms in colorectal cancer and obesity","volume":"9","author":"Gholami","year":"2020","journal-title":"Cancer Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"D966","DOI":"10.1093\/nar\/gkae1078","article-title":"GENCODE 2025: Reference gene annotation for human and mouse","volume":"53","author":"Mudge","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/s41586-020-2493-4","article-title":"Expanded encyclopaedias of DNA elements in the human and mouse genomes","volume":"583","author":"Moore","year":"2020","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1126\/science.1112009","article-title":"Antisense transcription in the mammalian transcriptome","volume":"309","author":"Katayama","year":"2005","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Engstrom, P.G., Suzuki, H., Ninomiya, N., Akalin, A., Sessa, L., Lavorgna, G., Brozzi, A., Luzi, L., Tan, S.L., and Yang, L. (2006). Complex Loci in human and mouse genomes. PLoS Genet., 2.","DOI":"10.1371\/journal.pgen.0020047"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13825","DOI":"10.1038\/s41598-022-17338-1","article-title":"A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease","volume":"12","author":"Hughes","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.7150\/thno.71360","article-title":"Metformin in aging and aging-related diseases: Clinical applications and relevant mechanisms","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1210\/endrev\/bnad032","article-title":"Diabetes Mellitus, Energy Metabolism, and COVID-19","volume":"45","author":"Conte","year":"2024","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Norouzi, M., Norouzi, S., Ruggiero, A., Khan, M.S., Myers, S., Kavanagh, K., and Vemuri, R. (2021). Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection. Microorganisms, 9.","DOI":"10.3390\/microorganisms9061211"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e33213321","DOI":"10.1002\/dmrr.3321","article-title":"Covid-19 and diabetes mellitus: Unveiling the interaction of two pandemics","volume":"36","author":"Maddaloni","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"n365","DOI":"10.1136\/bmj.n365","article-title":"Trends in obesity and adiposity measures by race or ethnicity among adults in the United States 2011-18: Population based study","volume":"372","author":"Liu","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jacl.2013.04.001","article-title":"Obesity, adiposity, and dyslipidemia: A consensus statement from the National Lipid Association","volume":"7","author":"Bays","year":"2013","journal-title":"J. Clin. Lipidol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kosmas, C.E., Rodriguez Polanco, S., Bousvarou, M.D., Papakonstantinou, E.J., Pe\u00f1a Genao, E., Guzman, E., and Kostara, C.E. (2023). The triglyceride\/high-density lipoprotein cholesterol (TG\/HDL-C) ratio as a risk marker for metabolic syndrome and cardiovascular disease. Diagnostics, 13.","DOI":"10.3390\/diagnostics13050929"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Putra, I., Daly, M., Sutin, A., Steptoe, A., and Robinson, E. (2023). The psychological legacy of past obesity and early mortality: Evidence from two longitudinal studies. BMC Med., 21.","DOI":"10.1186\/s12916-023-03148-3"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/oby.23116","article-title":"Genetics of Obesity: What We Have Learned Over Decades of Research","volume":"29","author":"Bouchard","year":"2021","journal-title":"Obesity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: From discovery to biology","volume":"23","author":"Loos","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"GBD Adult BMI Collaborators (2025). Global, regional, and national prevalence of adult overweight and obesity, 1990\u20132021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet, 405, 813\u2013838. Erratum in Lancet 2025, 406, 810. https:\/\/doi.org\/10.1016\/S0140-6736(25)01722-2.","DOI":"10.1016\/S0140-6736(25)01722-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41387-024-00352-9","article-title":"Assessing the economic impact of obesity and overweight on employers: Identifying opportunities to improve work force health and well-being","volume":"14","author":"Dall","year":"2024","journal-title":"Nutr. Diabetes"},{"key":"ref_25","unstructured":"NCD Risk Factor Collaboration (2024). Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet, 403, 1027\u20131050."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17119","DOI":"10.1074\/jbc.RA118.003608","article-title":"The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex","volume":"293","author":"Zhang","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/ije\/dyz273","article-title":"Has the prevalence of overweight, obesity and central obesity levelled off in the United States? Trends, patterns, disparities, and future projections for the obesity epidemic","volume":"49","author":"Wang","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.ajhg.2024.04.016","article-title":"An integrative framework to prioritize genes in more than 500 loci associated with body mass index","volume":"111","author":"Hemerich","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41366-019-0428-7","article-title":"The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward","volume":"44","author":"Ndiaye","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41380-024-02737-9","article-title":"Obesity: Exploring its connection to brain function through genetic and genomic perspectives","volume":"30","author":"Saeed","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"The ENCODE Project Consortium (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57\u201374.","DOI":"10.1038\/nature11247"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Manning, A.K., Goustin, A.S., Kleinbrink, E.L., Thepsuwan, P., Cai, J., Ju, D., Leong, A., Udler, M.S., Brown, J.B., and Goodarzi, M.O. (2020). A Long Non-coding RNA, LOC157273, Is an Effector Transcript at the Chromosome 8p23.1-PPP1R3B Metabolic Traits and Type 2 Diabetes Risk Locus. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00615"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1161\/ATVBAHA.116.307879","article-title":"MYOSLID Is a Novel Serum Response Factor-Dependent Long Noncoding RNA That Amplifies the Vascular Smooth Muscle Differentiation Program","volume":"36","author":"Zhao","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1038\/s41467-019-12988-8","article-title":"Foxp1 controls brown\/beige adipocyte differentiation and thermogenesis through regulating \u03b23-AR desensitization","volume":"10","author":"Liu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1126\/science.290.5489.134","article-title":"Function of GATA transcription factors in preadipocyte-adipocyte transition","volume":"290","author":"Tong","year":"2000","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e67305","DOI":"10.7554\/eLife.67305","article-title":"ZC3H4 restricts non-coding transcription in human cells","volume":"10","author":"Estell","year":"2021","journal-title":"eLife"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"FANTOM Consortium (2014). A promoter-level mammalian expression atlas. Nature, 507, 462\u2013470.","DOI":"10.1038\/nature13182"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature21374","article-title":"An atlas of human long non-coding RNAs with accurate 5\u2019 ends","volume":"543","author":"Hon","year":"2017","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102537","DOI":"10.1016\/j.autrev.2020.102537","article-title":"The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease","volume":"19","author":"McGonagle","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"eabn8153","DOI":"10.1126\/science.abn8197","article-title":"The landscape of tolerated genetic variation in humans and primates","volume":"380","author":"Gao","year":"2023","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10875-025-01877-z","article-title":"DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia","volume":"45","author":"Biglari","year":"2025","journal-title":"J. Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1161\/01.CIR.0000161814.02942.B2","article-title":"Phosphorylation of GATA2 by Akt increases adipose tissue differentiation and reduces adipose tissue-related inflammation: A novel pathway linking obesity to atherosclerosis","volume":"111","author":"Menghini","year":"2005","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ijcard.2016.11.049","article-title":"The adverse impact of obesity on heart rate variability is modified by a NFE2L2 gene variant: The SAPALDIA cohort","volume":"228","author":"Adam","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41419-018-1249-7","article-title":"Wnt3a disrupts GR-TEAD4-PPAR\u03b32 positive circuits and cytoskeletal rearrangement in a \u03b2-catenin-dependent manner during early adipogenesis","volume":"10","author":"Park","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language?","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng.840","article-title":"Principles for the post-GWAS functional characterization of cancer risk loci","volume":"43","author":"Freedman","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.slast.2024.100122","article-title":"Validating core therapeutic targets for osteoporosis treatment based on integrating network pharmacology and informatics","volume":"29","author":"Weng","year":"2024","journal-title":"SLAS Technol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lou, W., Ding, B., and Fu, P. (2020). Pseudogene-Derived lncRNAs and Their miRNA Sponging Mechanism in Human Cancer. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00085"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8320","DOI":"10.1038\/s41598-021-87702-0","article-title":"Predicting anthropometric and metabolic traits with a genetic risk score for obesity in a sample of Pakistanis","volume":"11","author":"Rana","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yoo, A., and Lee, S. (2023). Neuronal growth regulator 1 may modulate interleukin-6 signaling in adipocytes. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1148521"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1056\/NEJMoa2100433","article-title":"Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19","volume":"384","author":"Gordon","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17968","DOI":"10.1038\/s41598-021-96720-x","article-title":"Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States","volume":"11","author":"Ando","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/ng.3620","article-title":"A thrifty variant in CREBRF strongly influences body mass index in Samoans","volume":"48","author":"Minster","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41576-020-00305-9","article-title":"The influence of evolutionary history on human health and disease","volume":"22","author":"Benton","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_58","first-page":"353","article-title":"Diabetes mellitus: A \u201cthrifty\u201d genotype rendered detrimental by \u201cprogress\u201d?","volume":"14","author":"Neel","year":"1962","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1038\/ijo.2008.161","article-title":"Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: The \u2018drifty gene\u2019 hypothesis","volume":"32","author":"Speakman","year":"2008","journal-title":"Int. J. Obes."},{"key":"ref_60","unstructured":"Hughes, G.J. (2022). The Thrifty Gene Hypothesis: A Total Review. [Bachelor\u2019s Thesis, The University of Arizona]."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"691","DOI":"10.7150\/jca.62683","article-title":"Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma","volume":"13","author":"Zhang","year":"2022","journal-title":"J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41419-018-0627-5","article-title":"The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a\/CTGF axis as a ceRNA","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/CIRCRESAHA.115.308166","article-title":"MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue","volume":"118","author":"Sun","year":"2016","journal-title":"Circ. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"103062","DOI":"10.1016\/j.ebiom.2020.103062","article-title":"Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes","volume":"61","author":"Bowker","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"D1188","DOI":"10.1093\/nar\/gkac1072","article-title":"The UCSC genome browser database: 2023 update","volume":"51","author":"Nassar","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/bioinformatics\/btl048","article-title":"The UCSC Known Genes","volume":"22","author":"Hsu","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D243","DOI":"10.1093\/nar\/gkae1038","article-title":"NCBI RefSeq: Reference sequence standards through 25 years of curation and annotation","volume":"53","author":"Goldfarb","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Gagnidze, K., and Pfaff, D.W. (2022). Epigenetic mechanisms: DNA methylation and histone protein modification. Neuroscience in the 21st Century: From Basic to Clinical, Springer.","DOI":"10.1007\/978-3-030-88832-9_69"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1046\/j.1432-1327.2002.02797.x","article-title":"The human beta-globin locus control region","volume":"269","author":"Levings","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/nar\/gks1284","article-title":"Integrative annotation of chromatin elements from ENCODE data","volume":"41","author":"Hoffman","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_71","unstructured":"Rigor, P. (2015). Applications in High-Throughput Sequencing Technologies: From Compression Algorithms and Data Warehousing to Understanding Gene Regulation and Diseases at Scale. [Doctoral Dissertation, UC Irvine]."},{"key":"ref_72","first-page":"305","article-title":"Functional analyses of a low-penetrance risk variant rs6702619\/1p21. 2 associating with colorectal cancer in Polish population","volume":"66","author":"Statkiewicz","year":"2019","journal-title":"Acta Biochim. Pol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"D171","DOI":"10.1093\/nar\/gks1221","article-title":"Factorbook.org: A Wiki-based database for transcription factor-binding data generated by the ENCODE consortium","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1101\/gr.139105.112","article-title":"Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors","volume":"22","author":"Wang","year":"2012","journal-title":"Genome Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature11245","article-title":"Architecture of the human regulatory network derived from ENCODE data","volume":"489","author":"Gerstein","year":"2012","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","article-title":"The NHGRI-EBI GWAS Catalog: Knowledgebase and deposition resource","volume":"51","author":"Sollis","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"D1082","DOI":"10.1093\/nar\/gkad987","article-title":"The UCSC Genome Browser database: 2024 update","volume":"52","author":"Raney","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.tig.2021.06.007","article-title":"Evolutionary conservation in noncoding genomic regions","volume":"37","author":"Leypold","year":"2021","journal-title":"Trends Genet."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wood, E.J., Chin-Inmanu, K., Jia, H., and Lipovich, L. (2013). Sense-antisense gene pairs: Sequence, transcription, and structure are not conserved between human and mouse. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00183"},{"key":"ref_80","first-page":"D101","article-title":"DIANA-LncBase v3: Indexing experimentally supported miRNA targets on non-coding transcripts","volume":"48","author":"Karagkouni","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","article-title":"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets","volume":"120","author":"Lewis","year":"2005","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molcel.2007.06.017","article-title":"MicroRNA targeting specificity in mammals: Determinants beyond seed pairing","volume":"27","author":"Grimson","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"D831","DOI":"10.1093\/nar\/gkaa793","article-title":"The Bgee suite: Integrated curated expression atlas and comparative transcriptomics in animals","volume":"49","author":"Bastian","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_86","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_87","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/7015\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:58:06Z","timestamp":1786521486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/7015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":87,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27157015"],"URL":"https:\/\/doi.org\/10.3390\/ijms27157015","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}