Evidence mapPaperPMID 38697123Full record

ArticleCell genomics2024

Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.

Sheridan H Littleton, Khanh B Trang, Christina M Volpe, Kieona Cook, Nicole DeBruyne, Jean Ann Maguire, Mary Ann Weidekamp, Kenyaita M Hodge, Keith Boehm, Sumei Lu and 7 more

Abstract read
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sheridan H LittletonCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Khanh B TrangCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Christina M VolpeCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kieona CookCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Nicole DeBruyneCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jean Ann MaguireCenter for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mary Ann WeidekampCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kenyaita M HodgeCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Keith BoehmCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Sumei LuCenter 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; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jonathan P BradfieldCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Quantinuum Research LLC, San Diego, CA 92101, USA.
James A PippinCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Stewart A AndersonDepartment of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Andrew D WellsCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthew C PahlCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Struan F A GrantCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: grants@chop.edu.

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
Genome Wide Association Study for Childhood ObesityR01HD056465 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A · 2008 to 2024
$9.5M
Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
Investigating the role of the FAIM2 locus in predisposition to childhood obesityF31HD105404 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI LITTLETON, SHERIDAN HOPE · 2022 to 2023
$63k
NCATS NIH HHS UL1 TR001878NICHD NIH HHS F31 HD105404NICHD NIH HHS R01 HD056465NIDDK NIH HHS UM1 DK126194
6 · The paper itself

Abstract

The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.

Indexed as

3' Untranslated RegionsApoptosis Regulatory ProteinsMembrane ProteinsPediatric ObesityAllelesCell DifferentiationChildChromosomes, Human, Pair 12Genetic Predisposition to DiseaseGenome-Wide Association StudyHuman Embryonic Stem CellsHumansNeuronsPolymorphism, Single Nucleotide3' Untranslated RegionsApoptosis Regulatory ProteinsFAIM2 protein, humanMembrane Proteinschildhood obesitygenome-wide association studyhypothalamusneuron differentiationobesityrisk variantstem cells

Identifiers

PMID38697123
PMCPMC11099382

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.