Evidence map›Paper›PMID 22997280›Full record

SynthesisClinical chemistry2012

Clinical and genetic correlates of growth differentiation factor 15 in the community.

Jennifer E Ho, Anubha Mahajan, Ming-Huei Chen, Martin G Larson, Elizabeth L McCabe, Anahita Ghorbani, Susan Cheng, Andrew D Johnson, Cecilia M Lindgren, Tibor Kempf and 7 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in Clinical chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 5 pooled it
3.0field-weighted citation impact, top 9% 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

77 citing papers in PubMed, 5 syntheses or guidelines pooled it, 134 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Article
  8. Article
  9. GDF15 in Patients with Autoimmune Primary Adrenal Insufficiency.International journal of molecular sciences · 2026
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Proximate and ultimate causes of pregnancy sickness.Evolution, medicine, and public health · 2025
    Review
  15. Article
  16. TheInternational journal of molecular sciences · 2024
    Article
  17. Article
  18. Sex-based Differences in Heart Failure Biomarkers.Current heart failure reports · 2024
    Review
  19. Article
  20. Macrophages as a Source and Target of GDF-15.International journal of molecular sciences · 2024
    Review

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 8 institutions in 4 countries.

Jennifer E HoFramingham Heart Study, Framingham, MA, USA.
Anubha Mahajan
Ming-Huei Chen
Martin G Larson
Elizabeth L McCabe
Anahita Ghorbani
Susan Cheng
Andrew D Johnson
Cecilia M Lindgren
Tibor Kempf
Lars Lind
Erik Ingelsson
Ramachandran S Vasan
James Januzzi
Kai C Wollert
Andrew P Morris
Thomas J Wang
Harvard University · USUniversity of Oxford · GBBoston University · USMassachusetts General Hospital · USMedizinische Hochschule Hannover · DEKarolinska Institutet · SENational Heart Lung and Blood Institute · USUppsala University · SE

Funding

Myocardial and Arterial Aging: Spectrum, Correlates, and PrognosisK99HL107642 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHENG, SUSAN · 2012 to 2013
$276k
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS K99 HL107642NHLBI NIH HHS N01 HC025195Wellcome Trust 090532Wellcome Trust WT064890Wellcome Trust WT081682
6 · The paper itself

Abstract

backgroundGrowth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively.

methodsPlasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study.

resultsGDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h(2) = 0.38; P = 2.5 × 10(-11)). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 × 10(-32) for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines.

conclusionsIn ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.

Indexed as

AgedCardiovascular DiseasesCholesterol, HDLCohort StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGrowth Differentiation Factor 15HumansMaleMiddle AgedMultivariate AnalysisPolymorphism, Single NucleotideQuantitative Trait LociRisk FactorsCholesterol, HDLGDF15 protein, humanGrowth Differentiation Factor 15

Identifiers

PMID22997280
PMCPMC4150608
OpenAlexW2164388248

What OpenQuestion 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 OpenQuestion graph.