Evidence map›Paper›PMID 36194249›Full record

ArticleDiabetologia2023

Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

Brian T Steffen, Weihong Tang, Pamela L Lutsey, Ryan T Demmer, Elizabeth Selvin, Kunihiro Matsushita, Alanna C Morrison, Weihua Guan, Mary R Rooney, Faye L Norby and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 18 citations in OpenAlex.

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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

13 authors at 5 institutions in 1 country.

Brian T SteffenDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Weihong TangDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Pamela L LutseyDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Ryan T DemmerDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Elizabeth SelvinDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Kunihiro MatsushitaDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Weihua GuanDivision of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, USA.
Mary R RooneyDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Faye L NorbyDepartment of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA.
Nathan PankratzDepartment of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
David CouperUniversity of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
James S PankowDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. panko001@umn.edu.ORCID 0000-0001-7076-483X
University of Minnesota · USJohns Hopkins University · USCedars-Sinai Smidt Heart Institute · USThe University of Texas Health Science Center at Houston · USUniversity of North Carolina at Chapel Hill · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
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
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Cardiovascular Disease Epidemiology &Prevention TrngT32HL007779 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI PAMELA L. Lutsey, JAMES S PANKOW · 1994 to 2026
$9.3M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00003 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2022 to 2025
$5.1M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE E · 2022 to 2025
$5.0M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00004 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI WINDHAM, BEVERLY GWEN · 2022 to 2025
$4.8M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00002 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CORESH, JOSEF · 2022 to 2025
$4.7M
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
Profiling Cardiovascular Events and Biomarkers in the Very Old to Improve Personalized Approaches for the Prevention of Cardiac and Vascular DiseaseR01HL134320 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, SELVIN, ELIZABETH · 2016 to 2019
$3.1M
GWA for Gene-Environment Interaction Effects Influencing CHDU01HG004402 · NHGRI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2007 to 2009
$1.6M
NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS K01 HL164764NHLBI NIH HHS K24 HL159246NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL134320NHLBI NIH HHS T32 HL007779
6 · The paper itself

Abstract

aims/hypothesisGenetic predisposition to type 2 diabetes is well-established, and genetic risk scores (GRS) have been developed that capture heritable liabilities for type 2 diabetes phenotypes. However, the proteins through which these genetic variants influence risk have not been thoroughly investigated. This study aimed to identify proteins and pathways through which type 2 diabetes risk variants may influence pathophysiology.

methodsUsing a proteomics data-driven approach in a discovery sample of 7241 White participants in the Atherosclerosis Risk in Communities Study (ARIC) cohort and a replication sample of 1674 Black ARIC participants, we interrogated plasma levels of 4870 proteins and four GRS of specific type 2 diabetes phenotypes related to beta cell function, insulin resistance, lipodystrophy, BMI/blood lipid abnormalities and a composite score of all variants combined.

resultsTwenty-two plasma proteins were identified in White participants after Bonferroni correction. Of the 22 protein-GRS associations that were statistically significant, 10 were replicated in Black participants and all but one were directionally consistent. In a secondary analysis, 18 of the 22 proteins were found to be associated with prevalent type 2 diabetes and ten proteins were associated with incident type 2 diabetes. Two-sample Mendelian randomisation indicated that complement C2 may be causally related to greater type 2 diabetes risk (inverse variance weighted estimate: OR 1.65 per SD; p=7.0 × 10 CONCLUSIONS/

interpretationIdentified proteins may represent viable intervention or pharmacological targets to prevent, reverse or slow type 2 diabetes progression, and further research is needed to pursue these targets.

Indexed as

Diabetes Mellitus, Type 2Complement C2HumansProteomicsRisk FactorsComplement C2Beta cellDiabetesGenetic risk scoreInsulin resistanceMendelianProteomics

Identifiers

PMID36194249
PMCPMC9742300
OpenAlexW4300819201

What OpenQuestion holds

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LicenceTDM
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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.