Imperial College London
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DrDipenderGill

Faculty of Medicine, School of Public Health

Clinical Research Fellow
 
 
 
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Contact

 

+44 (0)7904 843 810dipender.gill

 
 
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Location

 

School of a Public HealthMedical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zuber:2021:ije/dyaa216,
author = {Zuber, V and Gill, D and Ala-Korpela, M and Langenberg, C and Butterworth, A and Bottolo, L and Burgess, S},
doi = {ije/dyaa216},
journal = {International Journal of Epidemiology},
pages = {893--901},
title = {High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease},
url = {http://dx.doi.org/10.1093/ije/dyaa216},
volume = {50},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundGenetic variants can be used to prioritize risk factors as potential therapeutic targets via Mendelian randomization (MR). An agnostic statistical framework using Bayesian model averaging (MR-BMA) can disentangle the causal role of correlated risk factors with shared genetic predictors. Here, our objective is to identify lipoprotein measures as mediators between lipid-associated genetic variants and coronary artery disease (CAD) for the purpose of detecting therapeutic targets for CAD.MethodsAs risk factors we consider 30 lipoprotein measures and metabolites derived from a high-throughput metabolomics study including 24 925 participants. We fit multivariable MR models of genetic associations with CAD estimated in 453 595 participants (including 113 937 cases) regressed on genetic associations with the risk factors. MR-BMA assigns to each combination of risk factors a model score quantifying how well the genetic associations with CAD are explained. Risk factors are ranked by their marginal score and selected using false-discovery rate (FDR) criteria. We perform supplementary and sensitivity analyses varying the dataset for genetic associations with CAD.ResultsIn the main analysis, the top combination of risk factors ranked by the model score contains apolipoprotein B (ApoB) only. ApoB is also the highest ranked risk factor with respect to the marginal score (FDR <0.005). Additionally, ApoB is selected in all sensitivity analyses. No other measure of cholesterol or triglyceride is consistently selected otherwise.ConclusionsOur agnostic genetic investigation prioritizes ApoB across all datasets considered, suggesting that ApoB, representing the total number of hepatic-derived lipoprotein particles, is the primary lipid determinant of CAD.
AU  - Zuber,V
AU  - Gill,D
AU  - Ala-Korpela,M
AU  - Langenberg,C
AU  - Butterworth,A
AU  - Bottolo,L
AU  - Burgess,S
DO  - ije/dyaa216
EP  - 901
PY  - 2021///
SN  - 0300-5771
SP  - 893
TI  - High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease
T2  - International Journal of Epidemiology
UR  - http://dx.doi.org/10.1093/ije/dyaa216
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000685312900024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/ije/article/50/3/893/5948819
UR  - http://hdl.handle.net/10044/1/91959
VL  - 50
ER  -
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