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)
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.
Impact Factor
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Times Cited
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Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Cardiology ; Gwas ; Genomics ; Mendelian Randomization ; Proteomics ; Sex Heterogeneity; Genome-wide Association; Mendelian Randomization; Risk; Determinants; Metaanalysis
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2023
Prepublished im Jahr
0
HGF-Berichtsjahr
2023
ISSN (print) / ISBN
1542-6416
e-ISSN
1542-6416
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 20,
Heft: 1,
Seiten: ,
Artikelnummer: 31
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Campus, 4 Crinan St, London N1 9xw, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Translational Genomics (ITG)
POF Topic(s)
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-506700-001
Förderungen
Sarnoff Cardiovascular
Copyright
Erfassungsdatum
2023-10-06