Evidence map›Paper›PMID 26343871›Full record

SynthesisAtherosclerosis2015

Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies.

Lars E Laugsand, Joachim H Ix, Traci M Bartz, Luc Djousse, Jorge R Kizer, Russell P Tracy, Abbas Dehghan, Kathryn Rexrode, Oscar L Lopez, Eric B Rimm and 5 more

Registry-linked trialOpen access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Atherosclerosis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00005152 (Nurses' Health Study), which is not on this map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 17% 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.

NCT00005152 active not recruitingnot on this map

Nurses' Health Study (Cardiovascular Component)

TypeobservationalSponsorBrigham and Women's HospitalRan1980 to 2029Enrolled121,700ConditionsCardiovascular Diseases, Diabetes Mellitus, Coronary Disease, Heart Diseases
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. The role of hepatokines in NAFLD.Cell metabolism · 2023
    Review
  7. Observational
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. The impact of the AHSG genetic polymorphism on the risk of ischemic stroke: a case-control study.International journal of clinical and experimental pathology · 2018
    Article
  14. 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

15 authors at 10 institutions in 3 countries.

Lars E LaugsandDepartment of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Joachim H IxNephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Divisions of Nephrology and Preventive Medicine, University of California San Diego, San Diego, CA, USA.
Traci M BartzDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Luc DjousseBoston Veterans Affairs Healthcare System, Boston, MA, USA; Division of Aging, Brigham and Women's Hospital, Boston, MA, USA.
Jorge R KizerDepartment of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Russell P TracyDepartment of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, USA.
Abbas DehghanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Kathryn RexrodeDivision of Aging, Brigham and Women's Hospital, Boston, MA, USA.
Oscar L LopezDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Eric B RimmDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
David S SiscovickCardiovascular Health Research Unit, Department of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
Christopher J O'DonnellNational Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA; Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Anne NewmanUPMC/University of Pittsburgh Schools of the Health Sciences, Pittsburgh, PA, USA.
Kenneth J MukamalDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Majken K JensenDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital · USUniversity of Pittsburgh · USBeth Israel Deaconess Medical Center · USErasmus MC · NLFramingham Heart Study · USGroup Health Cooperative · USHarvard University · USUniversity of Vermont · USUniversity of Washington · USVA San Diego Healthcare System · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI TWOROGER, SHELLEY S · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WILLETT, WALTER C. · 1991 to 2009
$41.8M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
RISK FACTORS FOR CVD IN WOMENR01HL034594 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI JoAnn Elisabeth Manson, Lu Qi · 1985 to 2026
$13.8M
Dietary Etiology of Heart DiseaseR01HL035464 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ERIC B RIMM, Qi Sun · 1986 to 2026
$13.6M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
Genomic Epidemiology of Cardiovascular DiseaseZIAHL006002 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2009 to 2015
$8.0M
CHS Events Follow-up StudyR01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2009 to 2014
$6.3M
Determinants and Cardiovascular Consequences of Diabetes in Older AdultsR01HL094555 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ARNOLD, ALICE A., DJOUSSE, LUC · 2009 to 2012
$5.9M
CHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6M
Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and BloodR01HL087641 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2006 to 2008
$3.7M
NCI NIH HHS CA55075NCI NIH HHS CA87969NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL080295NHLBI NIH HHS HL34594NHLBI NIH HHS HL35464NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC065226NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N02-HL-6-4278NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL035464NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL094555NHLBI NIH HHS R01HL59367NHLBI NIH HHS U01 HL080295NIA NIH HHS 1R01AG032098-01A1NIA NIH HHS N01 AG012100NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062103NIA NIH HHS N01 AG062106NIA NIH HHS R01 AG023629NIA NIH HHS R01AG023629NIA NIH HHS R01 AG032098
6 · The paper itself

Abstract

BACKGROUND AND

aimsFetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification).

methodsGenetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993.

resultsAmong Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048).

conclusionCommon variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk.

Indexed as

AgedAged, 80 and overalpha-2-HS-GlycoproteinCarotid Intima-Media ThicknessCoronary VesselsFemaleGenetic VariationGenotypeHeart DiseasesHumansInsulin ResistanceLongitudinal StudiesMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideProspective StudiesAHSG protein, humanalpha-2-HS-GlycoproteinCoronary heart diseaseFetuin-AMendelian randomizationMeta-analysisSingle nucleotide polymorphisms

Identifiers

PMID26343871
PMCPMC4609621
OpenAlexW2154796355

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Registered trials

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.