Evidence map›Paper›PMID 30024021›Full record

ArticleAnnals of human genetics2018

Analysis of causal effect of APOA5 variants on premature coronary artery disease.

Fan Wang, Isabel Z Wang, Stephen Ellis, Stephen Archacki, John Barnard, Carlos Hubbard, Eric J Topol, Qiuyun Chen, Qing K Wang

Abstract read
In one paragraph

Article in Annals of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 21% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Omics research in atherosclerosis.Molecular and cellular biochemistry · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. 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

9 authors at 3 institutions in 2 countries.

Fan WangDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Isabel Z WangDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Stephen EllisDepartment of Cardiovascular Medicine, Sydell & Arnold Miller Family Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
Stephen ArchackiDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
John BarnardDepartment of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
Carlos HubbardDepartment of Cardiovascular Medicine, Sydell & Arnold Miller Family Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
Eric J TopolScripps Translational Science Institute, Scripps Research Institute, Scripps Clinic, La Jolla, CA, USA.
Qiuyun ChenDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Qing K WangDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0002-2235-6572
Cleveland Clinic · USCleveland Clinic Lerner College of Medicine · USScripps Research Institute · US

Funding

Functional Genomics of Atrial Fibrillation in Human AtriaR01HL111314 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2012 to 2019
$6.1M
NGS in Large CAD Families: In-Depth Identification of Rare Risk Genomic VariantsR01HL121358 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, QING KENNETH · 2014 to 2017
$2.8M
Targeting Nav1.5 trafficking as a therapy for lethal genetic cardiac arrhythmiasR01HL126729 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, QING KENNETH · 2015 to 2018
$1.6M
NHLBI NIH HHS R01 HL111314NHLBI NIH HHS R01 HL121358NHLBI NIH HHS R01 HL126729
6 · The paper itself

Abstract

Apolipoprotein A5 (APOA5) regulates the metabolisms of triglyceride and HDL. APOA5 variants have been linked to coronary artery disease (CAD), but their causal roles are not well studied yet. This study aims to identify the causal effects of APOA5 variants on premature CAD. Sequencing analysis of APOA5 in 128 premature, familiar CAD patients from GeneQuest identified 11 genomic variants, including p.S19W (rs3135506). SKAT analysis showed that all sequenced variants, in aggregate, significantly increased the risk of premature CAD (P-skat = 0.037). Individually, the p.S19W variant was significantly associated with risk of premature CAD (OR = 2.30, P = 0.008) in an independent set of 342 premature CAD patients and 537 controls after adjusting for covariates of sex, age, hypertension, body mass index, triglycerides (TGs), and total, LDL-, and HDL-cholesterol levels. Meanwhile, p.S19W significantly correlated with HDL-C levels (P = 0.048) and TG levels (P = 0.025). Mediation analysis yielded a mediation effect of p.S19W on risk of premature CAD through HDL-C (OR = 0.98, P = 0.040) and TG (OR = 0.98, P = 0.042), suggesting a causal relationship between p.S19W and premature CAD partially through its effects on HDL-C and TG levels. These results suggest that APOA5 variation regulates TG and HDL levels, thus displaying a causal role in the development of CAD.

Indexed as

AdultAgedApolipoprotein A-VCase-Control StudiesCholesterolCoronary Artery DiseaseFemaleGenotypeHumansMaleMiddle AgedTriglyceridesAPOA5 protein, humanApolipoprotein A-VCholesterolTriglyceridesapolipoprotein A5 (APOA5)coronary artery disease (CAD)high-density lipoprotein-cholesterol (HDL-C)mediation analysistriglyceride

Identifiers

PMID30024021
PMCPMC6188800
OpenAlexW2884239037

What Socratic 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 Socratic graph.