Evidence map›Paper›PMID 26883866›Full record

ArticleHuman genetics2016

Blood group antigen loci demonstrate multivariate genetic associations with circulating cellular adhesion protein levels in the Multi-Ethnic Study of Atherosclerosis.

Nicholas B Larson, Paul A Decker, Christina L Wassel, James S Pankow, Weihong Tang, Naomi Q Hanson, Michael Y Tsai, Suzette J Bielinski

Abstract readMulticenter Study
In one paragraph

Article in Human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

8 authors.

Nicholas B LarsonDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Larson.nicholas@mayo.edu.ORCID http://orcid.org/0000-0002-3468-4215
Paul A DeckerDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Christina L WasselDepartment Pathology and Laboratory Medicine, College of Medicine, University of Vermont, Burlington, VT, USA.
James S PankowDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
Weihong TangDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
Naomi Q HansonLaboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Michael Y TsaiLaboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Suzette J BielinskiDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Project 5: ROS, Glutathione and Vascular Response to Diesel ExhaustP50ES015915 · NIEHS · UNIVERSITY OF WASHINGTON · PI KAUFMAN, JOEL DANIEL · 2008 to 2012
$11.8M
Multi-Ethnic Study of Atherosclerosis (MESA) StudyR01HL071205 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI ROTTER, JEROME I · 2003 to 2007
$10.4M
Multi-Scale Biology of Atherosclerosis in the Cellular Adhesion PathwayR01HL098077 · NHLBI · MAYO CLINIC ROCHESTER · PI BIELINSKI, SUZETTE JANINE · 2010 to 2014
$2.8M
SUBCLINICAL CARDIOVASCULAR DISEASE STUDYN01HC095166 · HC · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI TRACY, RUSSELL P · 1999 to 2001
$758k
SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTERN01HC095162 · HC · JOHNS HOPKINS UNIVERSITY · PI SZKLO, MOYSES A · 1999 to 2000
$694k
SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC095161 · HC · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEA, STEVEN · 1999 to 2001
$642k
SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC095165 · HC · WAKE FOREST UNIVERSITY · PI BURKE, GREGORY L · 1999 to 2001
$616k
SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC095160 · HC · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SAAD, MOHAMMED F · 1999 to 2001
$592k
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1-TR-000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1-TR-001079NHLBI NIH HHS HL071205NHLBI NIH HHS N01 HC065226NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01-HC-65226NHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N01-HC-95162NHLBI NIH HHS N01-HC-95163NHLBI NIH HHS N01-HC-95164NHLBI NIH HHS N01-HC-95165NHLBI NIH HHS N01-HC-95166NHLBI NIH HHS N01-HC-95167NHLBI NIH HHS N01-HC-95168NHLBI NIH HHS N01-HC-95169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL071205NHLBI NIH HHS R01 HL098077NHLBI NIH HHS R01HL98077NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIEHS NIH HHS P50 ES015915NIEHS NIH HHS P50ES015915
6 · The paper itself

Abstract

The cellular adhesion pathway is critical in the pathophysiology of atherosclerosis, and genetic factors contributing to regulation of circulating levels of related proteins may be relevant to risk prediction of cardiovascular disease. In contrast to conducting separate genome-wide protein quantitative trait loci (pQTL) mapping analyses of each individual protein, joint genetic association analyses of multiple quantitative traits can leverage cross-trait co-variation and identify simultaneous regulatory effects on protein levels across the pathway. We conducted a multi-pQTL (mpQTL) analysis of 15 proteins related to cellular adhesion assayed on 2313 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We applied the MQFAM multivariate association analysis method in PLINK on normalized protein level residuals derived from univariate linear regression, adjusting for age, sex, and principal components of ancestry. Race/ethnicity-stratified analyses identified nine genome-wide significant (P < 5e-08) loci associated with co-variation of protein levels. Although the majority of these SNPs were in proximity to structural genes of the assayed proteins, we discovered multiple loci demonstrating co-association with the circulation of at least two proteins. Of these, two significant loci specific to non-Hispanic white participants, rs17074898 at ALOX5AP (P = 1.78E-08) and rs7521237 at KIAA1614 (P = 2.2E-08), would not have met statistical significance using univariate analyses. Moreover, common patterns of multi-protein associations were discovered at the ABO locus across race/ethnicity. These results indicate the biological relevance of blood group antigens on regulation of circulating cellular adhesion pathway proteins while also demonstrating race/ethnicity-specific co-regulatory effects.

Indexed as

EthnicityAntigensAtherosclerosisBlood Group AntigensCell Adhesion MoleculesHumansAntigensBlood Group AntigensCell Adhesion Molecules

Identifiers

PMID26883866
PMCPMC4795966

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Registered trials

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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.