Imperial College London
Alternate

Professor Paul M. Matthews

Faculty of Medicine, Department of Brain Sciences

Edmond and Lily Safra Chair, Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Huang:2023:10.3389/fgene.2023.1124431,
author = {Huang, J and Gill, D and Zuber, V and Matthews, PAUL and Elliott, PAUL and Tzoulaki, I and Dehghan, ABBAS},
doi = {10.3389/fgene.2023.1124431},
journal = {Frontiers in Genetics},
pages = {1--11},
title = {Circulatory proteins relate cardiovascular disease to cognitive performance: a Mendelian randomisation study},
url = {http://dx.doi.org/10.3389/fgene.2023.1124431},
volume = {14},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background and objectives: Mechanistic research suggests synergistic effects of cardiovascular disease (CVD) and dementia pathologies on cognitive decline. Interventions targeting proteins relevant to shared mechanisms underlying CVD and dementia could also be used for the prevention of cognitive impairment.Methods: We applied Mendelian randomisation (MR) and colocalization analysis to investigate the causal relationships of 90 CVD-related proteins measured by the Olink CVD I panel with cognitive traits. Genetic instruments for circulatory protein concentrations were obtained using a meta-analysis of genome-wide association studies (GWAS) from the SCALLOP consortium (N = 17,747) based on three sets of criteria: 1) protein quantitative trait loci (pQTL); 2) cis-pQTL (pQTL within ±500 kb from the coding gene); and 3) brain-specific cis-expression QTL (cis-eQTL) which accounts for coding gene expression based on GTEx8. Genetic associations of cognitive performance were obtained from GWAS for either: 1) general cognitive function constructed using Principal Component Analysis (N = 300,486); or, 2) g Factor constructed using genomic structural equation modelling (N = 11,263–331,679). Findings for candidate causal proteins were replicated using a separate protein GWAS in Icelanders (N = 35,559).Results: A higher concentration of genetically predicted circulatory myeloperoxidase (MPO) was nominally associated with better cognitive performance (p < 0.05) using different selection criteria for genetic instruments. Particularly, brain-specific cis-eQTL predicted MPO, which accounts for protein-coding gene expression in brain tissues, was associated with general cognitive function (βWald = 0.22, PWald = 2.4 × 10−4). The posterior probability for colocalization (PP.H4) of MPO pQTL with the g Factor was 0.577. Findings for MPO were replicated using the Icelandic GWAS. Although we did not find evidence for colocalization, we found that higher gene
AU  - Huang,J
AU  - Gill,D
AU  - Zuber,V
AU  - Matthews,PAUL
AU  - Elliott,PAUL
AU  - Tzoulaki,I
AU  - Dehghan,ABBAS
DO  - 10.3389/fgene.2023.1124431
EP  - 11
PY  - 2023///
SN  - 1664-8021
SP  - 1
TI  - Circulatory proteins relate cardiovascular disease to cognitive performance: a Mendelian randomisation study
T2  - Frontiers in Genetics
UR  - http://dx.doi.org/10.3389/fgene.2023.1124431
UR  - https://www.frontiersin.org/articles/10.3389/fgene.2023.1124431/abstract
UR  - https://www.frontiersin.org/articles/10.3389/fgene.2023.1124431/full
UR  - http://hdl.handle.net/10044/1/102932
VL  - 14
ER  -
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