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Carland, C.* ; Png, G. ; Mälarstig, A.* ; Kho, P.F.* ; Gustafsson, S.* ; Michaelsson, K.* ; Lind, L.* ; Tsafantakis, E.* ; Karaleftheri, M.* ; Dedoussis, G.* ; Ramisch, A.* ; Macdonald-Dunlop, E.* ; Klaric, L.* ; Joshi, P.K.* ; Chen, Y.* ; Björck, H.M.* ; Eriksson, P.* ; Carrasco-Zanini, J.* ; Wheeler, E.* ; Suhre, K.* ; Gilly, A. ; Zeggini, E. ; Viñuela, A.* ; Dermitzakis, E.T.* ; Wilson, J.F.* ; Langenberg, C.* ; Thareja, G.* ; Halama, A.* ; Schmidt, F.* ; Zanetti, D.* ; Assimes, T.*

Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases.

Clin. Proteom. 20:31 (2023)
Publ. Version/Full Text DOI PMC
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BACKGROUND: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. METHODS: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. RESULTS: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). CONCLUSION: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cardiology ; Gwas ; Genomics ; Mendelian Randomization ; Proteomics ; Sex Heterogeneity; Genome-wide Association; Mendelian Randomization; Risk; Determinants; Metaanalysis
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1542-6416
e-ISSN 1542-6416
Journal Clinical Proteomics
Quellenangaben Volume: 20, Issue: 1, Pages: , Article Number: 31 Supplement: ,
Publisher Springer
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506700-001
Grants Sarnoff Cardiovascular
DOI 10.1186/s12014-023-09421-0
WOS ID 001042629700001
Scopus ID 85167671931
PubMed ID 37550624
Erfassungsdatum 2023-10-06
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