Evidence mapPaperPMID 35537191Full record

ArticleSleep2022

Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits.

Chiara Lasconi, Matthew C Pahl, James A Pippin, Chun Su, Matthew E Johnson, Alessandra Chesi, Keith Boehm, Elisabetta Manduchi, Kristy Ou, Maria L Golson and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Sleep, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Chiara LasconiCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Matthew C PahlCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
James A PippinCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-6850-8164
Chun SuCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Matthew E JohnsonCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alessandra ChesiCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-0954-7446
Keith BoehmCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Elisabetta ManduchiInstitute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,USA.
Kristy OuDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Maria L GolsonDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2927-2013
Andrew D WellsCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Klaus H KaestnerDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Struan F A GrantCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0003-2025-5302
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

The Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · 2022 to 2025
$8.0M
Human Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARK A. ATKINSON, Rita Bottino · 2022 to 2022
$1.1M
NHLBI NIH HHS R01 HL143790NIDDK NIH HHS U01 DK123594NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232NIDDK NIH HHS UM1 DK126194NIH HHS UM1 DK126194
6 · The paper itself

Abstract

We investigated the potential role of sleep-trait associated genetic loci in conferring a degree of their effect via pancreatic α- and β-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 α- and β-cells, intersecting public GWAS reports with our own ATAC-seq and high-resolution promoter-focused Capture C data generated from both sorted human α-cells and an established human beta-cell line (EndoC-βH1). Finally, we identified putative effector genes physically interacting with sleep-trait associated variants in α- and EndoC-βH1cells running variant-to-gene mapping and establish pathways in which these genes are significantly involved. We observed that insomnia, short and long sleep-but not morningness-were significantly correlated with type 2 diabetes, obesity and other metabolic traits. Both the EndoC-βH1 and α-cells were enriched for insomnia loci (p = .01; p = .0076), short sleep loci (p = .017; p = .022) and morningness loci (p = 2.2 × 10-7; p = .0016), while the α-cells were also enriched for long sleep loci (p = .034). Utilizing our promoter contact data, we identified 63 putative effector genes in EndoC-βH1 and 76 putative effector genes in α-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.

Indexed as

Diabetes Mellitus, Type 2Islets of LangerhansSleep Initiation and Maintenance DisordersChromosome MappingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansObesitySleepalpha cellbeta cellchromatin conformation captureepigeneticsGWASmetabolismpancreassleep

Identifiers

PMID35537191
PMCPMC9366645
OpenAlexW4280495219

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.