{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:39:20Z","timestamp":1792093160876,"version":"4.4.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Children's Hospital of Philadephia","award":["Daniel B. Burke Endowed Chair for Diabetes Researc"],"award-info":[{"award-number":["Daniel B. Burke Endowed Chair for Diabetes Researc"]}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD056465"],"award-info":[{"award-number":["R01HD056465"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["UM1 DK126194"],"award-info":[{"award-number":["UM1 DK126194"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>Genome-wide association studies (GWAS) have identified hundreds of type 2 diabetes loci, with the vast majority of signals located in non-coding regions; as a consequence, it remains largely unclear which \u2018effector\u2019 genes these variants influence. Determining these effector genes has been hampered by the relatively challenging cellular settings in which they are hypothesised to confer their effects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To implicate such effector genes, we elected to generate and integrate high-resolution promoter-focused Capture-C, assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA-seq datasets to characterise chromatin and expression profiles in multiple cell lines relevant to type 2 diabetes for subsequent functional follow-up analyses: EndoC-BH1 (pancreatic beta cell), HepG2 (hepatocyte) and Simpson\u2013Golabi\u2013Behmel syndrome (SGBS; adipocyte).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The subsequent variant-to-gene analysis implicated 810 candidate effector genes at 370 type 2 diabetes risk loci. Using partitioned linkage disequilibrium score regression, we observed enrichment for type 2 diabetes and fasting glucose GWAS loci in promoter-connected putative <jats:italic>cis<\/jats:italic>-regulatory elements in EndoC-BH1 cells as well as fasting insulin GWAS loci in SGBS cells. Moreover, as a proof of principle, when we knocked down expression of the <jats:italic>SMCO4<\/jats:italic> gene in EndoC-BH1 cells, we observed a statistically significant increase in insulin secretion.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>These results provide a resource for comparing tissue-specific data in tractable cellular models as opposed to relatively challenging primary cell settings.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Data availability<\/jats:title>\n                <jats:p>Raw and processed next-generation sequencing data for EndoC-BH1, HepG2, SGBS_undiff and SGBS_diff cells are deposited in GEO under the Superseries accession GSE262484. Promoter-focused Capture-C data are deposited under accession GSE262496. Hi-C data are deposited under accession GSE262481. Bulk ATAC-seq data are deposited under accession GSE262479. Bulk RNA-seq data are deposited under accession GSE262480.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-024-06261-x","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:02:22Z","timestamp":1725595342000},"page":"2740-2753","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Implicating type 2 diabetes effector genes in relevant metabolic cellular models using promoter-focused Capture-C"],"prefix":"10.1007","volume":"67","author":[{"given":"Nicholas A.","family":"Wachowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Pippin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Manduchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula W.","family":"Parlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wabitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Chesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Struan F. A.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Pahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"issue":"8","key":"6261_CR1","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/s41580-021-00362-w","volume":"22","author":"I Jerkovic","year":"2021","unstructured":"Jerkovic I, Cavalli G (2021) Understanding 3D genome organization by multidisciplinary methods. Nat Rev Mol Cell Biol 22(8):511\u2013528. https:\/\/doi.org\/10.1038\/s41580-021-00362-w","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"8","key":"6261_CR2","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/s41576-019-0128-0","volume":"20","author":"S Schoenfelder","year":"2019","unstructured":"Schoenfelder S, Fraser P (2019) Long-range enhancer-promoter contacts in gene expression control. Nat Rev Genet 20(8):437\u2013455. https:\/\/doi.org\/10.1038\/s41576-019-0128-0","journal-title":"Nat Rev Genet"},{"issue":"7","key":"6261_CR3","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1038\/s41588-019-0457-0","volume":"51","author":"I Miguel-Escalada","year":"2019","unstructured":"Miguel-Escalada I, Bonas-Guarch S, Cebola I et al (2019) Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes. Nat Genet 51(7):1137\u20131148. https:\/\/doi.org\/10.1038\/s41588-019-0457-0","journal-title":"Nat Genet"},{"issue":"5","key":"6261_CR4","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1016\/j.cell.2016.09.037","volume":"167","author":"BM Javierre","year":"2016","unstructured":"Javierre BM, Burren OS, Wilder SP et al (2016) Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell 167(5):1369-1384 e1319. https:\/\/doi.org\/10.1016\/j.cell.2016.09.037","journal-title":"Cell"},{"issue":"9","key":"6261_CR5","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1073\/pnas.1621192114","volume":"114","author":"A Varshney","year":"2017","unstructured":"Varshney A, Scott LJ, Welch RP et al (2017) Genetic regulatory signatures underlying islet gene expression and type 2 diabetes. Proc Natl Acad Sci U S A 114(9):2301\u20132306. https:\/\/doi.org\/10.1073\/pnas.1621192114","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"6261_CR6","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.celrep.2018.12.083","volume":"26","author":"N Lawlor","year":"2019","unstructured":"Lawlor N, Marquez EJ, Orchard P et al (2019) Multiomic profiling identifies cis-regulatory networks underlying human pancreatic \u03b2 cell identity and function. Cell Rep 26(3):788-801 e786. https:\/\/doi.org\/10.1016\/j.celrep.2018.12.083","journal-title":"Cell Rep"},{"issue":"4","key":"6261_CR7","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s41588-021-00823-0","volume":"53","author":"J Chiou","year":"2021","unstructured":"Chiou J, Zeng C, Cheng Z et al (2021) Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk. Nat Genet 53(4):455\u2013466. https:\/\/doi.org\/10.1038\/s41588-021-00823-0","journal-title":"Nat Genet"},{"issue":"12","key":"6261_CR8","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.2337\/db16-0361","volume":"65","author":"SK Thomsen","year":"2016","unstructured":"Thomsen SK, Ceroni A, van de Bunt M et al (2016) Systematic functional characterization of candidate causal genes for type 2 diabetes risk variants. Diabetes 65(12):3805\u20133811. https:\/\/doi.org\/10.2337\/db16-0361","journal-title":"Diabetes"},{"issue":"9","key":"6261_CR9","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1016\/j.cmet.2022.08.014","volume":"34","author":"C Su","year":"2022","unstructured":"Su C, Gao L, May CL et al (2022) 3D chromatin maps of the human pancreas reveal lineage-specific regulatory architecture of T2D risk. Cell Metab 34(9):1394-1409 e1394. https:\/\/doi.org\/10.1016\/j.cmet.2022.08.014","journal-title":"Cell Metab"},{"key":"6261_CR10","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.molmet.2017.12.007","volume":"8","author":"VG Tsonkova","year":"2018","unstructured":"Tsonkova VG, Sand FW, Wolf XA et al (2018) The EndoC-\u03b2H1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates. Mol Metab 8:144\u2013157. https:\/\/doi.org\/10.1016\/j.molmet.2017.12.007","journal-title":"Mol Metab"},{"key":"6261_CR11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/sj.ijo.0801520","volume":"25","author":"M Wabitsch","year":"2001","unstructured":"Wabitsch M, Melzner I, Braun M et al (2001) Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Int J Obes 25:8\u201315. https:\/\/doi.org\/10.1038\/sj.ijo.0801520","journal-title":"Int J Obes"},{"issue":"1","key":"6261_CR12","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/s41588-022-01261-2","volume":"55","author":"AK Rottner","year":"2023","unstructured":"Rottner AK, Ye Y, Navarro-Guerrero E et al (2023) A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk. Nat Genet 55(1):54\u201365. https:\/\/doi.org\/10.1038\/s41588-022-01261-2","journal-title":"Nat Genet"},{"issue":"8","key":"6261_CR13","doi-asserted-by":"publisher","first-page":"zsac109","DOI":"10.1093\/sleep\/zsac109","volume":"45","author":"C Lasconi","year":"2022","unstructured":"Lasconi C, Pahl MC, Pippin JA et al (2022) Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits. Sleep 45(8):zsac109. https:\/\/doi.org\/10.1093\/sleep\/zsac109","journal-title":"Sleep"},{"issue":"1","key":"6261_CR14","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1038\/s41467-019-09302-x","volume":"10","author":"A Chesi","year":"2019","unstructured":"Chesi A, Wagley Y, Johnson ME et al (2019) Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density. Nat Commun 10(1):1260. https:\/\/doi.org\/10.1038\/s41467-019-09302-x","journal-title":"Nat Commun"},{"issue":"1","key":"6261_CR15","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.ajhg.2019.05.010","volume":"105","author":"M Caliskan","year":"2019","unstructured":"Caliskan M, Manduchi E, Rao HS et al (2019) Genetic and epigenetic fine mapping of complex trait associated loci in the human liver. Am J Hum Genet 105(1):89\u2013107. https:\/\/doi.org\/10.1016\/j.ajhg.2019.05.010","journal-title":"Am J Hum Genet"},{"issue":"1","key":"6261_CR16","doi-asserted-by":"publisher","first-page":"6749","DOI":"10.1038\/s41467-021-27001-4","volume":"12","author":"MC Pahl","year":"2021","unstructured":"Pahl MC, Doege CA, Hodge KM et al (2021) Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits. Nat Commun 12(1):6749. https:\/\/doi.org\/10.1038\/s41467-021-27001-4","journal-title":"Nat Commun"},{"issue":"1","key":"6261_CR17","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13059-022-02691-1","volume":"23","author":"MC Pahl","year":"2022","unstructured":"Pahl MC, Le Coz C, Su C et al (2022) Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types. Genome Biol 23(1):125. https:\/\/doi.org\/10.1186\/s13059-022-02691-1","journal-title":"Genome Biol"},{"key":"6261_CR18","doi-asserted-by":"publisher","first-page":"eabq0844","DOI":"10.1126\/sciadv.abq0844","volume":"9","author":"J Palmero","year":"2023","unstructured":"Palmero J, Chesi A, Zimmerman A et al (2023) Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep. Sci Adv 9:eabq0844. https:\/\/doi.org\/10.1126\/sciadv.abq0844","journal-title":"Sci Adv"},{"key":"6261_CR19","doi-asserted-by":"publisher","first-page":"102000","DOI":"10.1016\/j.pneurobio.2021.102000","volume":"201","author":"C Su","year":"2021","unstructured":"Su C, Argenziano M, Lu S et al (2021) 3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders. Prog Neurobiol 201:102000. https:\/\/doi.org\/10.1016\/j.pneurobio.2021.102000","journal-title":"Prog Neurobiol"},{"issue":"1","key":"6261_CR20","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41467-020-17089-5","volume":"11","author":"C Su","year":"2020","unstructured":"Su C, Johnson ME, Torres A et al (2020) Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells. Nat Commun 11(1):3294. https:\/\/doi.org\/10.1038\/s41467-020-17089-5","journal-title":"Nat Commun"},{"key":"6261_CR21","unstructured":"R Core Team (2021) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria"},{"issue":"3","key":"6261_CR22","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1093\/bioinformatics\/btaa692","volume":"37","author":"L Lopez-Delisle","year":"2021","unstructured":"Lopez-Delisle L, Rabbani L, Wolff J et al (2021) pyGenomeTracks: reproducible plots for multivariate genomic datasets. Bioinformatics 37(3):422\u2013423. https:\/\/doi.org\/10.1093\/bioinformatics\/btaa692","journal-title":"Bioinformatics"},{"issue":"6","key":"6261_CR23","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3(6):1101\u20131108. https:\/\/doi.org\/10.1038\/nprot.2008.73","journal-title":"Nat Protoc"},{"issue":"10","key":"6261_CR24","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1007\/s00439-021-02326-8","volume":"140","author":"C Su","year":"2021","unstructured":"Su C, Pahl MC, Grant SFA, Wells AD (2021) Restriction enzyme selection dictates detection range sensitivity in chromatin conformation capture-based variant-to-gene mapping approaches. Hum Genet 140(10):1441\u20131448. https:\/\/doi.org\/10.1007\/s00439-021-02326-8","journal-title":"Hum Genet"},{"issue":"7675","key":"6261_CR25","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","volume":"550","author":"GTeX Consortium","year":"2017","unstructured":"GTeX Consortium (2017) Genetic effects on gene expression across human tissues. Nature 550(7675):204\u2013213. https:\/\/doi.org\/10.1038\/nature24277","journal-title":"Nature"},{"issue":"10","key":"6261_CR26","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1038\/s41588-019-0494-8","volume":"51","author":"I Jung","year":"2019","unstructured":"Jung I, Schmitt A, Diao Y et al (2019) A compendium of promoter-centered long-range chromatin interactions in the human genome. Nat Genet 51(10):1442\u20131449. https:\/\/doi.org\/10.1038\/s41588-019-0494-8","journal-title":"Nat Genet"},{"issue":"Database","key":"6261_CR27","doi-asserted-by":"publisher","first-page":"D88","DOI":"10.1093\/nar\/gkl822","volume":"35","author":"A Visel","year":"2007","unstructured":"Visel A, Minovitsky S, Dubchak I, Pennacchio LA (2007) VISTA Enhancer Browser a database of tissue-specific human enhancers. Nucleic Acids Res 35(Database):D88\u2013D92. https:\/\/doi.org\/10.1093\/nar\/gkl822","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"6261_CR28","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1373\/clinchem.2010.157016","volume":"57","author":"E Ahlqvist","year":"2011","unstructured":"Ahlqvist E, Ahluwalia TS, Groop L (2011) Genetics of type 2 diabetes. Clin Chem 57(2):241\u2013254. https:\/\/doi.org\/10.1373\/clinchem.2010.157016","journal-title":"Clin Chem"},{"issue":"50","key":"6261_CR29","doi-asserted-by":"publisher","first-page":"35802","DOI":"10.1074\/jbc.274.50.35802","volume":"274","author":"WR Tschantz","year":"1999","unstructured":"Tschantz WR, Zhang L, Casey PJ (1999) Cloning, expression, and cellular localization of a human prenylcysteine lyase. J Biol Chem 274(50):35802\u201335808. https:\/\/doi.org\/10.1074\/jbc.274.50.35802","journal-title":"J Biol Chem"},{"issue":"11","key":"6261_CR30","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/ng.3404","volume":"47","author":"HK Finucane","year":"2015","unstructured":"Finucane HK, Bulik-Sullivan B, Gusev A et al (2015) Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet 47(11):1228\u20131235. https:\/\/doi.org\/10.1038\/ng.3404","journal-title":"Nat Genet"},{"key":"6261_CR31","doi-asserted-by":"publisher","first-page":"e55851","DOI":"10.7554\/eLife.55851","volume":"9","author":"PN Timshel","year":"2020","unstructured":"Timshel PN, Thompson JJ, Pers TH (2020) Genetic mapping of etiologic brain cell types for obesity. Elife 9:e55851. https:\/\/doi.org\/10.7554\/eLife.55851","journal-title":"Elife"},{"issue":"7538","key":"6261_CR32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature14177","volume":"518","author":"AE Locke","year":"2015","unstructured":"Locke AE, Kahali B, Berndt SI et al (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518(7538):197\u2013206. https:\/\/doi.org\/10.1038\/nature14177","journal-title":"Nature"},{"issue":"11","key":"6261_CR33","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","volume":"50","author":"A Mahajan","year":"2018","unstructured":"Mahajan A, Taliun D, Thurner M et al (2018) Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet 50(11):1505\u20131513. https:\/\/doi.org\/10.1038\/s41588-018-0241-6","journal-title":"Nat Genet"},{"issue":"7","key":"6261_CR34","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/s41588-020-0637-y","volume":"52","author":"M Vujkovic","year":"2020","unstructured":"Vujkovic M, Keaton JM, Lynch JA et al (2020) 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. Nat Genet 52(7):680\u2013691. https:\/\/doi.org\/10.1038\/s41588-020-0637-y","journal-title":"Nat Genet"},{"issue":"11","key":"6261_CR35","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","volume":"53","author":"E Mountjoy","year":"2021","unstructured":"Mountjoy E, Schmidt EM, Carmona M et al (2021) An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci. Nat Genet 53(11):1527\u20131533. https:\/\/doi.org\/10.1038\/s41588-021-00945-5","journal-title":"Nat Genet"},{"issue":"5","key":"6261_CR36","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s41588-022-01058-3","volume":"54","author":"A Mahajan","year":"2022","unstructured":"Mahajan A, Spracklen CN, Zhang W et al (2022) Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet 54(5):560\u2013572. https:\/\/doi.org\/10.1038\/s41588-022-01058-3","journal-title":"Nat Genet"},{"issue":"8","key":"6261_CR37","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1007\/s00439-022-02434-z","volume":"141","author":"V Forgetta","year":"2022","unstructured":"Forgetta V, Jiang L, Vulpescu NA et al (2022) An effector index to predict target genes at GWAS loci. Hum Genet 141(8):1431\u20131447. https:\/\/doi.org\/10.1007\/s00439-022-02434-z","journal-title":"Hum Genet"},{"issue":"1","key":"6261_CR38","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1038\/s41467-018-03554-9","volume":"9","author":"DZ Pan","year":"2018","unstructured":"Pan DZ, Garske KM, Alvarez M et al (2018) Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS. Nat Commun 9(1):1512. https:\/\/doi.org\/10.1038\/s41467-018-03554-9","journal-title":"Nat Commun"},{"issue":"1","key":"6261_CR39","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1038\/s41467-020-16537-6","volume":"11","author":"K Williams","year":"2020","unstructured":"Williams K, Ingerslev LR, Bork-Jensen J et al (2020) Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism. Nat Commun 11(1):2695. https:\/\/doi.org\/10.1038\/s41467-020-16537-6","journal-title":"Nat Commun"},{"issue":"1","key":"6261_CR40","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1373\/clinchem.2017.280727","volume":"64","author":"CM Astley","year":"2018","unstructured":"Astley CM, Todd JN, Salem RM et al (2018) Genetic evidence that carbohydrate-stimulated insulin secretion leads to obesity. Clin Chem 64(1):192\u2013200. https:\/\/doi.org\/10.1373\/clinchem.2017.280727","journal-title":"Clin Chem"},{"issue":"20","key":"6261_CR41","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","volume":"27","author":"L Yengo","year":"2018","unstructured":"Yengo L, Sidorenko J, Kemper KE et al (2018) Meta-analysis of genome-wide association studies for height and body mass index in approximately 700000 individuals of European ancestry. Hum Mol Genet 27(20):3641\u20133649. https:\/\/doi.org\/10.1093\/hmg\/ddy271","journal-title":"Hum Mol Genet"},{"issue":"12","key":"6261_CR42","doi-asserted-by":"publisher","first-page":"e1007813","DOI":"10.1371\/journal.pgen.1007813","volume":"14","author":"F Day","year":"2018","unstructured":"Day F, Karaderi T, Jones MR et al (2018) Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet 14(12):e1007813. https:\/\/doi.org\/10.1371\/journal.pgen.1007813","journal-title":"PLoS Genet"},{"issue":"1","key":"6261_CR43","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/pro.3307","volume":"27","author":"PJ Thul","year":"2018","unstructured":"Thul PJ, Lindskog C (2018) The human protein atlas: a spatial map of the human proteome. Protein Sci 27(1):233\u2013244. https:\/\/doi.org\/10.1002\/pro.3307","journal-title":"Protein Sci"},{"issue":"7869","key":"6261_CR44","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/s41586-021-03577-1","volume":"595","author":"S Oh","year":"2021","unstructured":"Oh S, Shao J, Mitra J et al (2021) Enhancer release and retargeting activates disease-susceptibility genes. Nature 595(7869):735\u2013740. https:\/\/doi.org\/10.1038\/s41586-021-03577-1","journal-title":"Nature"},{"issue":"6","key":"6261_CR45","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/s41588-022-01078-z","volume":"54","author":"M Vujkovic","year":"2022","unstructured":"Vujkovic M, Ramdas S, Lorenz KM et al (2022) A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. Nat Genet 54(6):761\u2013771. https:\/\/doi.org\/10.1038\/s41588-022-01078-z","journal-title":"Nat Genet"},{"issue":"D1","key":"6261_CR46","doi-asserted-by":"publisher","first-page":"D985","DOI":"10.1093\/nar\/gkw1055","volume":"45","author":"G Koscielny","year":"2017","unstructured":"Koscielny G, An P, Carvalho-Silva D et al (2017) Open Targets: a platform for therapeutic target identification and validation. Nucleic Acids Res 45(D1):D985\u2013D994. https:\/\/doi.org\/10.1093\/nar\/gkw1055","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"6261_CR47","doi-asserted-by":"publisher","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","volume":"45","author":"J MacArthur","year":"2017","unstructured":"MacArthur J, Bowler E, Cerezo M et al (2017) The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res 45(D1):D896\u2013D901. https:\/\/doi.org\/10.1093\/nar\/gkw1133","journal-title":"Nucleic Acids Res"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06261-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-024-06261-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06261-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T09:04:05Z","timestamp":1732784645000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-024-06261-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":47,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["6261"],"URL":"https:\/\/doi.org\/10.1007\/s00125-024-06261-x","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"assertion":[{"value":"28 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We thank G. Costecalde from Univercell-Biosolutions for providing the EndoC-\u03b2H1 cells. We acknowledge B. Johnson from the Children\u2019s Hospital of Philadelphia for assistance with culturing EndoC-BH1 cells.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Raw and processed next-generation sequencing data for EndoC-BH1, HepG2, SGBS_undiff and SGBS_diff cells are deposited in GEO under the Superseries accession GSE262484. Promoter-focused Capture-C data are deposited under accession GSE262496. Hi-C data are deposited under accession GSE262481. Bulk ATAC-seq data are deposited under accession GSE262479. Bulk RNA-seq data are deposited under accession GSE262480.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This work was supported by NIH Grants UM1 DK126194, R01HD056465 and the Center for Spatial and Functional Genomics at CHOP. SFAG is supported by the Daniel B. Burke Endowed Chair for Diabetes Research. We acknowledge that the funders had no input on the experimental design of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"This project was conceived by SFAG. MCP and SFAG directed experimental studies. MCP conducted bioinformatic analyses and analysed experimental results. NAW designed and performed targeted knockdown and glucose-stimulated insulin secretion experiments. JAP, KB, SL, MEL and UWP designed and performed next-generation sequencing experiments. EM and AC developed the bioinformatic pipeline infrastructure. MW provided SGBS cells and was involved in data acquisition. ADW provided supervision and was involved in data acquisition. SFAG and ADW acquired funding. MCP wrote the manuscript together with NAW and SFAG. All authors contributed to, read and approved the final version of the manuscript. SFAG and MCP are guarantors of this work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}