{"entity": "researcher", "timestamp": "2026-07-12T09:26:12.396Z", "family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "affiliations": ["Department of Clinical Sciences Malm\u00f6, Lund University Diabetes Centre, Scania University Hospital, Malm\u00f6, Sweden. charlotte.ling@med.lu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691"}}, "publications": [{"entity": "publication", "iuid": "9e0a3a071e494da1ae5ca45e7c048ec3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e0a3a071e494da1ae5ca45e7c048ec3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e0a3a071e494da1ae5ca45e7c048ec3"}}, "title": "Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.", "authors": [{"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Lindstr\u00f6m", "given": "Axel", "initials": "A", "orcid": "0009-0008-1641-0406", "researcher": {"href": "https://publications.scilifelab.se/researcher/02c7aecdebce45cd87657f6756fe2977.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A"}, {"family": "Martin", "given": "Melina", "initials": "M"}, {"family": "Karagiannopoulos", "given": "Alexandros", "initials": "A", "orcid": "0000-0001-8458-1065", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8c0cfd9fd9741729f91d5dd554c199d.json"}}, {"family": "Scisciola", "given": "Lucia", "initials": "L", "orcid": "0000-0003-3636-4298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e332946efcac491b8953928cb46c0851.json"}}, {"family": "Kost", "given": "Katja", "initials": "K"}, {"family": "J\u00f6nsson", "given": "Josefine", "initials": "J", "orcid": "0000-0003-0709-2828", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a4b2eb9eef5496eb27e76fc9fca120a.json"}}, {"family": "Nilsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Kantor", "given": "Boris", "initials": "B"}, {"family": "Dudenh\u00f6ffer-Pfeifer", "given": "Monika", "initials": "M"}, {"family": "Rots", "given": "Marianne G", "initials": "MG"}, {"family": "Wendt", "given": "Anna", "initials": "A"}, {"family": "R\u00f6nn", "given": "Tina", "initials": "T"}, {"family": "Eliasson", "given": "Lena", "initials": "L", "orcid": "0000-0002-6467-5029", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6567e3b86e42c8bb5ef008b665f2de.json"}}, {"family": "Bacos", "given": "Karl", "initials": "K", "orcid": "0000-0002-2461-9073", "researcher": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b.json"}}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2026-04-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "8", "issue": "4", "pages": "957-980", "issn-l": "2522-5812"}, "abstract": "Epigenome-wide studies of pancreatic islets provide valuable insights into type 2 diabetes (T2D) but lack methylomes from individual cell types. Here we show changes to alpha and beta cell-specific methylomes and transcriptomes from people with or without T2D, using whole-genome bisulfite sequencing and RNA sequencing. We discover 22,544 differentially methylated regions annotated to 7,975 genes in alpha versus beta cells, such as INS, GCG, PDX1 and PCSK1, with ~50% showing differential expression. CRISPR-dCas9-DNMT3A-based epigenetic editing increases INS and TH DNA methylation, while CRISPR-dCas9-TET1-based editing decreases GCG methylation, each altering INS, TH or GCG expression and content in beta cells. Pre-T2D/T2D-associated differentially methylated regions in alpha and beta cells overlap 12-18% of T2D-associated genome-wide association study candidates. Additionally, ONECUT2 is epigenetically upregulated in beta cells from people with pre-T2D/T2D and elevated in male Goto-Kakizaki rat islets. ONECUT2 overexpression in beta cells/islets downregulates gene sets impacting insulin secretion and glucose homeostasis, and reduces mitochondrial activity, ATP/ADP ratio and insulin secretion. We also provide 'alpha-beta-methylome' ( https://alpha-beta-methylome.serve.scilifelab.se/app/alpha-beta-methylome/ ), a resource exploring T2D, age and sex associations on methylation, highlighting cell-specific epigenetic regulation and dysfunctions contributing to T2D.", "doi": "10.1038/s42255-026-01498-9", "pmid": "42032109", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13121032"}, {"db": "pii", "key": "10.1038/s42255-026-01498-9"}], "notes": [], "created": "2026-06-24T14:02:31.698Z", "modified": "2026-06-24T14:02:32.023Z"}, {"entity": "publication", "iuid": "afb960cb22864dd38a6d8ae590cc4341", "links": {"self": {"href": "https://publications.scilifelab.se/publication/afb960cb22864dd38a6d8ae590cc4341.json"}, "display": {"href": "https://publications.scilifelab.se/publication/afb960cb22864dd38a6d8ae590cc4341"}}, "title": "Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors.", "authors": [{"family": "Engstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Nilsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Wierup", "given": "Nils", "initials": "N"}, {"family": "Bacos", "given": "Karl", "initials": "K", "orcid": "0000-0002-2461-9073", "researcher": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b.json"}}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2025-10-16", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "15", "issue": "1", "pages": "36133", "issn-l": "2045-2322"}, "abstract": "Single-cell and single-nuclei RNA-sequencing (scRNA-seq and snRNA-seq) analyze cell-specific transcriptomes. However, only snRNA-seq applies to frozen biobanked samples. For human pancreatic islets, marker genes and reference-based cell type annotation methods are mainly from scRNA-seq datasets and may not be suitable for snRNA-seq. We compared human islet scRNA-seq and snRNA-seq data from the same donors (N = 4) and evaluated annotation methods by studying cell type composition and gene detection, and identified novel marker genes. We compared cell type annotations: (1) manual annotation based on identified marker genes, (2) reference-based annotation using Azimuth's scRNA-seq pancreasref dataset, or (3) Seurat's label transfer from the Human Pancreas Analysis Program (HPAP) scRNA-seq dataset. ScRNA-seq and snRNA-seq identified the same cell types, but predicted cell type proportions differed. Cell type proportion-differences between annotation methods were larger for snRNA-seq. Reference-based annotations generated higher cell type prediction and mapping scores for scRNA-seq than snRNA-seq. Manual annotation identified the novel snRNA-seq markers DOCK10, KIRREL3 (beta cells), STK32B (alpha cells), MECOM, AC007368.1 (acinar cells), LAMC2 and SLC28A3 (ductal cells), which improve snRNA-seq-based annotation. We confirmed ZNF385D as a snRNA-seq beta cell marker and ZNF385D silencing reduced insulin secretion. In conclusion, this study discovered novel snRNA-seq cell type marker genes in human pancreatic islets, and highlights the need for tailored snRNA-seq annotation strategies.", "doi": "10.1038/s41598-025-21595-1", "pmid": "41102292", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12533216"}, {"db": "pii", "key": "10.1038/s41598-025-21595-1"}], "notes": [], "created": "2025-10-30T13:58:54.553Z", "modified": "2025-11-13T17:36:11.555Z"}, {"entity": "publication", "iuid": "1ed57cee75824ec0a43c626f80dac7e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ed57cee75824ec0a43c626f80dac7e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ed57cee75824ec0a43c626f80dac7e7"}}, "title": "Blood-Based Epigenetic Biomarkers Associated With Incident Chronic Kidney Disease in Individuals With Type 2 Diabetes.", "authors": [{"family": "Marchiori", "given": "Marian", "initials": "M"}, {"family": "Maguolo", "given": "Alice", "initials": "A", "orcid": "0000-0002-8921-2012", "researcher": {"href": "https://publications.scilifelab.se/researcher/cac232a66c6745f7b74d2b52ec0d007a.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A"}, {"family": "Maziarz", "given": "Marlena", "initials": "M"}, {"family": "Martinell", "given": "Mats", "initials": "M"}, {"family": "Gomez", "given": "Maria F", "initials": "MF"}, {"family": "Ahlqvist", "given": "Emma", "initials": "E"}, {"family": "Garc\u00eda-Calz\u00f3n", "given": "Sonia", "initials": "S", "orcid": "0000-0002-1249-4795", "researcher": {"href": "https://publications.scilifelab.se/researcher/76aa68910e0f427e853c8e7db7b17332.json"}}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2025-03-01", "journal": {"title": "Diabetes", "issn": "1939-327X", "volume": "74", "issue": "3", "pages": "439-450", "issn-l": "0012-1797"}, "abstract": "There is an increasing need for new biomarkers to improve prediction of chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D). We aimed to identify blood-based epigenetic biomarkers associated with incident CKD and develop a methylation risk score (MRS) predicting CKD in individuals with newly diagnosed T2D. DNA methylation was analyzed epigenome wide in blood from 487 individuals with newly diagnosed T2D, of whom 88 developed CKD during an 11.5-year follow-up. Weighted Cox regression was used to associate methylation with incident CKD. Weighted logistic models and cross-validation (k = 5) were performed to test whether the MRS could predict CKD. Methylation at 37 sites was associated with CKD development based on a false discovery rate of <5% and absolute methylation differences of \u22655% between individuals with incident CKD and those free of CKD during follow-up. Notably, 15 genes annotated to these sites, e.g., TGFBI, SHISA3, and SLC43A2 (encoding LAT4), have been linked to CKD or related risk factors, including blood pressure, BMI, and estimated glomerular filtration rate. Using an MRS including 37 sites and cross-validation for prediction of CKD, we generated receiver operating characteristic (ROC) curves with an area under the curve (AUC) of 0.82 for the MRS and AUC of 0.87 for the combination of MRS and clinical factors. Importantly, ROC curves including the MRS had significantly better AUCs versus the one only including clinical factors (AUC = 0.72). The combined epigenetic biomarker had high accuracy in identifying individuals free of future CKD (negative predictive value of 94.6%). We discovered a high-performance epigenetic biomarker for predicting CKD, encouraging its potential role in precision medicine, risk stratification, and targeted prevention in T2D.\n\nThere is an increasing need for new biomarkers to improve the prediction and prevention of chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D), a leading cause of morbidity and mortality in this population. We investigated whether new blood-based epigenetic biomarkers predict incident CKD in individuals with newly diagnosed T2D. We discovered a novel blood-based epigenetic biomarker, composed of a combination of a methylation risk score and clinical factors, capable of predicting CKD during an 11.5-year follow-up (area under the curve of 0.87, negative predictive value of 94.6%) in individuals with newly diagnosed T2D. The epigenetic biomarker could provide a valuable tool for early risk stratification and prevention of CKD in individuals with newly diagnosed T2D, supporting its future use for precision medicine.", "doi": "10.2337/db24-0483", "pmid": "39715581", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11842608"}, {"db": "pii", "key": "157641"}], "notes": [], "created": "2025-10-30T13:38:03.879Z", "modified": "2025-10-30T13:38:04.234Z"}, {"entity": "publication", "iuid": "9458971190ee41e099e40121d1866819", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9458971190ee41e099e40121d1866819.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9458971190ee41e099e40121d1866819"}}, "title": "Impact of excess sugar on the whole genome DNA methylation pattern in human sperm.", "authors": [{"family": "J\u00f6nsson", "given": "Josefine", "initials": "J", "orcid": "0000-0003-0709-2828", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a4b2eb9eef5496eb27e76fc9fca120a.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A"}, {"family": "Kugelberg", "given": "Unn", "initials": "U"}, {"family": "Skog", "given": "Signe", "initials": "S"}, {"family": "Lindstr\u00f6m", "given": "Axel", "initials": "A"}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Ofori", "given": "Jones K", "initials": "JK"}, {"family": "Bacos", "given": "Karl", "initials": "K"}, {"family": "R\u00f6nn", "given": "Tina", "initials": "T"}, {"family": "\u00d6st", "given": "Anita", "initials": "A"}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Epigenomics", "issn": "1750-192X", "volume": "17", "issue": "2", "pages": "89-104", "issn-l": null}, "abstract": "Dietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects the methylome in human sperm, and to describe the sperm methylome. We used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation in sperm taken at three time points from 15 males during a diet intervention; i) at baseline, ii) after one week on a standardized diet, and iii) after an additional week on a high-sugar diet providing 150% of their estimated total energy expenditure.\n\nWe identified seven nominal diet-associated differentially methylated regions in sperm (p < 0.05). The diet was nominally associated with methylation of 143 sites linked to fertility (e.g. AHRR, GNAS, and HDAC4), 313 sites in imprinted genes (e.g. GLIS3, PEG10, PEG3, and SNURF), and 42 sites in top 1%-expressed genes (e.g. CHD2) (p < 0.05). In sperm, 3'UTRs and introns had the highest levels of methylation, while 5'UTRs and CpG islands had the lowest levels. Non-expressed genes in human sperm were hypomethylated in exons compared with transcribed genes.\n\nIn human sperm, DNA methylation levels were linked to gene expression, and excess sugar had modest effects on methylation on imprinted and highly expressed genes, and genes affecting fertility.", "doi": "10.1080/17501911.2024.2439782", "pmid": "39707713", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service"}, "xrefs": [], "notes": [], "created": "2025-02-03T07:41:54.349Z", "modified": "2025-02-03T07:41:54.880Z"}, {"entity": "publication", "iuid": "b1486cd2f8e04ed5a94771fa99efe1eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b1486cd2f8e04ed5a94771fa99efe1eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b1486cd2f8e04ed5a94771fa99efe1eb"}}, "title": "DNA methylation in cord blood partially mediates the effects of prepregnancy BMI on early childhood offspring BMI.", "authors": [{"family": "Maguolo", "given": "Alice", "initials": "A", "orcid": "0000-0002-8921-2012", "researcher": {"href": "https://publications.scilifelab.se/researcher/cac232a66c6745f7b74d2b52ec0d007a.json"}}, {"family": "J\u00f6nsson", "given": "Josefine", "initials": "J"}, {"family": "Perfilyev", "given": "Alexander", "initials": "A"}, {"family": "Maziarz", "given": "Marlena", "initials": "M"}, {"family": "Vaag", "given": "Allan", "initials": "A"}, {"family": "Malchau Carlsen", "given": "Emma", "initials": "E"}, {"family": "N\u00f8rgaard", "given": "Kirsten", "initials": "K"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "Renault", "given": "Kristina M", "initials": "KM"}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal article", "published": "2025-01-00", "journal": {"title": "Obesity (Silver Spring)", "issn": "1930-739X", "volume": "33", "issue": "1", "pages": "177-189", "issn-l": "1930-7381"}, "abstract": "We investigated whether prepregnancy BMI (prePregBMI) in women with obesity was associated with differential DNA methylation (DNAm) in cord blood (CB) and whether DNAm may mediate the association of prePregBMI and early childhood BMI z score (BMIz).\n\nFrom the Treatment of Obese Pregnant Women (TOP) study, 232 mother-child pairs were included. We conducted an epigenome-wide association study on prePregBMI and CB DNAm (450k array), followed by causal mediation analyses to test whether DNAm may mediate effects of prePregBMI on BMIz at age 36 months (BMIz36).\n\nDNAm at 5345 CpG sites annotated to 2842 genes, which were overrepresented in biological processes linked to carbohydrate metabolism and plasma lipoprotein particle clearance, was associated with prePregBMI (false discovery rate < 10%). Causal mediation analyses of 168 methylation sites associated with BMIz36 (p < 0.05) and overlapping with the 5345 prePregBMI-associated sites identified two sites on SYT7 and DEAF1, partially mediating the effect of prePregBMI on BMIz36 (p \u2264 0.01). After cross-validation, a methylation risk score including these two sites could predict the highest quartile of BMIz36 and fat mass (in grams) with area under the curve = 0.72 (95% CI: 0.58-0.85) and area under the curve = 0.71 (95% CI: 0.58-0.85), respectively.\n\nCB DNAm at birth may partially mediate effects of prePregBMI on early childhood BMIz36, supporting its plausible role in influencing individual future obesity risk.", "doi": "10.1002/oby.24174", "pmid": "39663190", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11664306"}], "notes": [], "created": "2025-10-30T13:55:22.871Z", "modified": "2025-10-30T13:55:22.979Z"}, {"entity": "publication", "iuid": "cf4eea7dc9114c88a4492dde1a35c646", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf4eea7dc9114c88a4492dde1a35c646.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf4eea7dc9114c88a4492dde1a35c646"}}, "title": "Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes", "authors": [{"family": "R\u00f6nn", "given": "Tina", "initials": "T", "orcid": "0000-0001-7622-800X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d24f13a3d6e4538a6584634beabe5d3.json"}}, {"family": "Ofori", "given": "Jones K", "initials": "JK", "orcid": "0000-0001-6484-1544", "researcher": {"href": "https://publications.scilifelab.se/researcher/31b7b1843fd94a99b488eaf653c6385b.json"}}, {"family": "Perfilyev", "given": "Alexander", "initials": "A", "orcid": "0000-0003-1136-8946", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d86c6fc2d684b4dbc93c2c66e4c4b88.json"}}, {"family": "Hamilton", "given": "Alexander", "initials": "A", "orcid": "0000-0001-5203-9220", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f077dfd61a44eddb403c972994cd3e7.json"}}, {"family": "Pircs", "given": "Karolina", "initials": "K", "orcid": "0000-0001-8281-4785", "researcher": {"href": "https://publications.scilifelab.se/researcher/070f9eb7abde403697f7e8ba0f9ac40e.json"}}, {"family": "Eichelmann", "given": "Fabian", "initials": "F", "orcid": "0000-0002-3975-5596", "researcher": {"href": "https://publications.scilifelab.se/researcher/810ca03b2e8c4adf888cf694facbb38a.json"}}, {"family": "Garcia-Calzon", "given": "Sonia", "initials": "S"}, {"family": "Karagiannopoulos", "given": "Alexandros", "initials": "A", "orcid": "0000-0001-8458-1065", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8c0cfd9fd9741729f91d5dd554c199d.json"}}, {"family": "Stenlund", "given": "Hans", "initials": "H", "orcid": "0000-0001-9943-296X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5259d6369f564651ace11d8bff689535.json"}}, {"family": "Wendt", "given": "Anna", "initials": "A"}, {"family": "Volkov", "given": "Petr", "initials": "P"}, {"family": "Schulze", "given": "Matthias B", "initials": "MB"}, {"family": "Mulder", "given": "Hindrik", "initials": "H"}, {"family": "Eliasson", "given": "Lena", "initials": "L", "orcid": "0000-0002-6467-5029", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6567e3b86e42c8bb5ef008b665f2de.json"}}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Bacos", "given": "Karl", "initials": "K", "orcid": "0000-0002-2461-9073", "researcher": {"href": "https://publications.scilifelab.se/researcher/527a271d23de48f8937b489c43e9da1b.json"}}, {"family": "Ling", "given": "Charlotte", "initials": "C", "orcid": "0000-0003-0587-7154", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd7c1ea934034c4db99f31a5a9b04691.json"}}], "type": "journal-article", "published": "2023-12-12", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "8040", "issn-l": "2041-1723"}, "abstract": "Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by \u03b2-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in \u03b2-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient \u03b2-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.", "doi": "10.1038/s41467-023-43719-9", "pmid": "38086799", "labels": {"Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10716521"}, {"db": "pii", "key": "10.1038/s41467-023-43719-9"}], "notes": [], "created": "2024-01-10T09:59:46.931Z", "modified": "2025-10-17T13:03:13.252Z"}]}