Evidence mapPaperPMID 27286809Full record

ArticleBMC genomics2016

Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation.

Symen Ligthart, Ahmad Vaez, Yi-Hsiang Hsu, Inflammation Working Group of the CHARGE Consortium, PMI-WG-XCP, LifeLines Cohort Study, Ronald Stolk, André G Uitterlinden, Albert Hofman, Behrooz Z Alizadeh and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 5 pooled it
7.8field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 5 syntheses or guidelines pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Article
  7. Article
  8. Sex differences in LDL-C genetic architecture and statin efficacy in All of Us.medRxiv : the preprint server for health sciences · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

12 authors at 3 institutions in 2 countries.

Symen LigthartDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000CA, Rotterdam, The Netherlands.
Ahmad VaezDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Yi-Hsiang HsuHebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA, USA.
Inflammation Working Group of the CHARGE Consortium
PMI-WG-XCP
LifeLines Cohort Study
Ronald StolkDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
André G UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000CA, Rotterdam, The Netherlands.
Behrooz Z AlizadehDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Oscar H FrancoDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000CA, Rotterdam, The Netherlands.
Abbas DehghanDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000CA, Rotterdam, The Netherlands. a.dehghan@erasmusmc.nl.
University Medical Center Groningen · NLErasmus MC · NLHarvard University · US

Funding

NIAMS NIH HHS R21 AR056405
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) have identified multiple genetic loci for C-reactive protein (CRP) and lipids, of which some overlap. We aimed to identify genetic pleiotropy among CRP and lipids in order to better understand the shared biology of chronic inflammation and lipid metabolism.

resultsIn a bivariate GWAS, we combined summary statistics of published GWAS on CRP (n = 66,185) and lipids, including LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol (n = 100,184), using an empirical weighted linear-combined test statistic. We sought replication for novel CRP associations in an independent sample of 17,743 genotyped individuals, and performed in silico replication of novel lipid variants in 93,982 individuals. Fifty potentially pleiotropic SNPs were identified among CRP and lipids: 21 for LDL-cholesterol and CRP, 20 for HDL-cholesterol and CRP, 21 for triglycerides, and CRP and 20 for total cholesterol and CRP. We identified and significantly replicated three novel SNPs for CRP in or near CTSB/FDFT1 (rs10435719, Preplication: 2.6 × 10(-5)), STAG1/PCCB (rs7621025, Preplication: 1.4 × 10(-3)) and FTO (rs1558902, Preplication: 2.7 × 10(-5)). Seven pleiotropic lipid loci were replicated in the independent set of MetaboChip samples of the Global Lipids Genetics Consortium. Annotating the effect of replicated CRP SNPs to the expression of nearby genes, we observed an effect of rs10435719 on gene expression of FDFT1, and an effect of rs7621025 on PCCB.

conclusionsOur large scale combined GWAS analysis identified numerous pleiotropic loci for CRP and lipids providing further insight in the genetic interrelation between lipids and inflammation. In addition, we provide evidence for FDFT1, PCCB and FTO to be associated with CRP levels.

Indexed as

Genome-Wide Association StudyMultifactorial InheritanceQuantitative Trait LociBiomarkersCholesterol, HDLC-Reactive ProteinDNA ReplicationGene ExpressionGenetic Association StudiesInflammationLipid MetabolismPolymorphism, Single NucleotideTriglyceridesBiomarkersCholesterol, HDLC-Reactive ProteinTriglyceridesC-reactive proteinGenetic pleiotropyGenome-wide association studyInflammationLipids

Identifiers

PMID27286809
PMCPMC4901478
OpenAlexW2416382276

What Socratic holds

Textmetadata
LicenceCC BY
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.