Evidence map›Paper›PMID 32484228›Full record

ArticleHuman molecular genetics2020

Protein QTL analysis of IGF-I and its binding proteins provides insights into growth biology.

Eric Bartell, Masanobu Fujimoto, Jane C Khoury, Philip R Khoury, Sailaja Vedantam, Christina M Astley, Joel N Hirschhorn, Andrew Dauber

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Eric BartellDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Masanobu FujimotoDivision of Endocrinology, Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Jane C KhouryDivision of Endocrinology, Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Philip R KhouryHeart Institute Research Core, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Sailaja VedantamMedical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christina M AstleyDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Joel N HirschhornDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Andrew DauberDivision of Endocrinology, Children's National Hospital, Washington, DC 20010, USA.
Broad Institute · USCincinnati Children's Hospital Medical Center · USChildren's National · US

Funding

Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
Seasonal and Viral Determinants of Type 1 Diabetes Onset, Remission, and Glycemic ControlK23DK120899 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ASTLEY, CHRISTINA M. · 2019 to 2021
$682k
NHGRI NIH HHS T32 HG002295NIDDK NIH HHS K23 DK120899NIDDK NIH HHS R01 DK075787
6 · The paper itself

Abstract

The growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGF binding protein-3 (IGFBP-3), pregnancy-associated plasma protein A (PAPP-A2), IGF-II and IGFBP-5 in 838 children (3-18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated single nucleotide polymorphisms near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger causal relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.

Indexed as

AdolescentBirth WeightBody HeightChildChild, PreschoolFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGrowth HormoneHumansInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor Binding Protein 5Insulin-Like Growth Factor IInsulin-Like Growth Factor IIMaleMendelian Randomization AnalysisGrowth HormoneIGF1 protein, humanIGFBP3 protein, humanInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor Binding Protein 5Insulin-Like Growth Factor IInsulin-Like Growth Factor IIPAPPA2 protein, humanPregnancy-Associated Plasma Protein-A

Identifiers

PMID32484228
PMCPMC7471503
OpenAlexW3028738863

What OpenQuestion 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 OpenQuestion graph.