{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:04:35Z","timestamp":1791090275520,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 DK126194"],"award-info":[{"award-number":["UM1 DK126194"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01 HL143790"],"award-info":[{"award-number":["NIH R01 HL143790"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We investigated the potential role of sleep-trait associated genetic loci in conferring a degree of their effect via pancreatic \u03b1- and \u03b2-cells, given that both sleep disturbances and metabolic disorders, including type 2 diabetes and obesity, involve polygenic contributions and complex interactions. We determined genetic commonalities between sleep and metabolic disorders, conducting linkage disequilibrium genetic correlation analyses with publicly available GWAS summary statistics. Then we investigated possible enrichment of sleep-trait associated SNPs in promoter-interacting open chromatin regions within \u03b1- and \u03b2-cells, intersecting public GWAS reports with our own ATAC-seq and high-resolution promoter-focused Capture C data generated from both sorted human \u03b1-cells and an established human beta-cell line (EndoC-\u03b2H1). Finally, we identified putative effector genes physically interacting with sleep-trait associated variants in \u03b1- and EndoC-\u03b2H1cells running variant-to-gene mapping and establish pathways in which these genes are significantly involved. We observed that insomnia, short and long sleep\u2014but not morningness\u2014were significantly correlated with type 2 diabetes, obesity and other metabolic traits. Both the EndoC-\u03b2H1 and \u03b1-cells were enriched for insomnia loci (p = .01; p = .0076), short sleep loci (p = .017; p = .022) and morningness loci (p = 2.2 \u00d7 10\u22127; p = .0016), while the \u03b1-cells were also enriched for long sleep loci (p = .034). Utilizing our promoter contact data, we identified 63 putative effector genes in EndoC-\u03b2H1 and 76 putative effector genes in \u03b1-cells, with these genes showing significant enrichment for organonitrogen and organophosphate biosynthesis, phosphatidylinositol and phosphorylation, intracellular transport and signaling, stress responses and cell differentiation. Our data suggest that a subset of sleep-related loci confer their effects via cells in pancreatic islets.<\/jats:p>","DOI":"10.1093\/sleep\/zsac109","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T21:21:47Z","timestamp":1652217707000},"source":"Crossref","is-referenced-by-count":17,"title":["Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits"],"prefix":"10.1093","volume":"45","author":[{"given":"Chiara","family":"Lasconi","sequence":"first","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Pahl","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8164","authenticated-orcid":false,"given":"James A","family":"Pippin","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Su","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E","family":"Johnson","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-7446","authenticated-orcid":false,"given":"Alessandra","family":"Chesi","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Boehm","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Manduchi","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2927-2013","authenticated-orcid":false,"given":"Maria L","family":"Golson","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Wells","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"},{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus H","family":"Kaestner","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2025-5302","authenticated-orcid":false,"given":"Struan F A","family":"Grant","sequence":"additional","affiliation":[{"name":"Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"},{"name":"Department of Genetics, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 , USA"},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"issue":"2","key":"2022081109200718100_CIT0001","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41583-018-0098-9","article-title":"Exploring phylogeny to find the function of sleep","volume":"20","author":"Anafi","year":"2019","journal-title":"Nat Rev Neurosci."},{"key":"2022081109200718100_CIT0002","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.metabol.2018.02.010","article-title":"Sleep influences on obesity, insulin resistance, and risk 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