Evidence map›Paper›PMID 37858332›Full record

ArticleCell metabolism2023

Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells.

Dongxiang Xue, Narisu Narisu, D Leland Taylor, Meili Zhang, Caleb Grenko, Henry J Taylor, Tingfen Yan, Xuming Tang, Neelam Sinha, Jiajun Zhu and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
12.4field-weighted citation impact, top 1% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

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  10. A loss of function variant inmedRxiv : the preprint server for health sciences · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 2 countries.

Dongxiang XueDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Narisu NarisuCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
D Leland TaylorCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Meili ZhangDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Caleb GrenkoCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Henry J TaylorCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN Cambridge, UK.
Tingfen YanCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Xuming TangDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Neelam SinhaCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jiajun ZhuDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
J Jeya VandanaDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Weill Cornell Medicine, The Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Angie Chi Nok ChongDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Angela LeeCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Erin C MansellCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amy J SwiftCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michael R ErdosCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Aaron ZhongStem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Lori L BonnycastleCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ting ZhouStem Cell Research Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Shuibing ChenDepartment of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Francis S CollinsCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: francis.collins@nih.gov.
National Institutes of Health · USCornell University · USMemorial Sloan Kettering Cancer Center · USNational Human Genome Research Institute · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2M
GENETIC ANALYSIS OF TYPE II DIABETES IN FINNISH POPULATIONZ01HG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI COLLINS, FRANCIS S. · 1995 to 2008
$6.2M
Determining the Intrinsic and Environmental Signal Contributing to Early T1D ProgressionU01DK127777 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING, PARKER, STEPHEN CJ · 2020 to 2023
$3.0M
Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and SurvivalR01DK119667 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2019 to 2022
$2.5M
A High Content Chemical Screen to Identify the Drug Candidates Promoting Human Beta Cell ProliferationR01DK124463 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2020 to 2023
$1.7M
A High Throughput Screening to Identify Compounds Rescuing Human Pancreatic Beta Cell Function in Diabetic ConditionsR01DK116075 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2018 to 2020
$1.3M
Intramural NIH HHS Z01 HG000024Intramural NIH HHS ZIA HG000024NCI NIH HHS P30 CA008748NIDDK NIH HHS R01 DK116075NIDDK NIH HHS R01 DK119667NIDDK NIH HHS R01 DK124463NIDDK NIH HHS U01 DK127777
6 · The paper itself

Abstract

Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional roles of many loci remain unexplored. Here, we engineered isogenic knockout human embryonic stem cell lines for 20 genes associated with T2D risk. We examined the impacts of each knockout on β cell differentiation, functions, and survival. We generated gene expression and chromatin accessibility profiles on β cells derived from each knockout line. Analyses of T2D-association signals overlapping HNF4A-dependent ATAC peaks identified a likely causal variant at the FAIM2 T2D-association signal. Additionally, the integrative association analyses identified four genes (CP, RNASE1, PCSK1N, and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with β cell sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental line and identified a single likely functional variant at each of 23 T2D-association signals.

Indexed as

Diabetes Mellitus, Type 2Human Embryonic Stem CellsInsulin-Secreting CellsCarbonyl Reductase (NADPH)Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideCarbonyl Reductase (NADPH)DHRS2 protein, humanallelic imbalancecellular traitdifferentiationgenome-wide association studiesHNF4Ainsulin productionlipotoxicitysingle nucleotide polymorphismβ cells

Identifiers

PMID37858332
PMCPMC10841752
OpenAlexW4387747459

What Socratic holds

Textmetadata
LicenceTDM
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.