Imperial College London
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ProfessorAbbasDehghan

Faculty of Medicine, School of Public Health

Professor in Molecular Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zagkos:2022:10.1371/journal.pmed.1004141,
author = {Zagkos, L and Dib, M-J and Pinto, R and Gill, D and Koskeridis, F and Drenos, F and Markozannes, G and Elliott, P and Zuber, V and Tsilidis, K and Dehghan, A and Tzoulaki, I},
doi = {10.1371/journal.pmed.1004141},
journal = {PLoS Medicine},
title = {Associations of genetically predicted fatty acid levels across the phenome: a mendelian randomisation study},
url = {http://dx.doi.org/10.1371/journal.pmed.1004141},
volume = {19},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. METHODS AND FINDINGS: The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.
AU  - Zagkos,L
AU  - Dib,M-J
AU  - Pinto,R
AU  - Gill,D
AU  - Koskeridis,F
AU  - Drenos,F
AU  - Markozannes,G
AU  - Elliott,P
AU  - Zuber,V
AU  - Tsilidis,K
AU  - Dehghan,A
AU  - Tzoulaki,I
DO  - 10.1371/journal.pmed.1004141
PY  - 2022///
SN  - 1549-1277
TI  - Associations of genetically predicted fatty acid levels across the phenome: a mendelian randomisation study
T2  - PLoS Medicine
UR  - http://dx.doi.org/10.1371/journal.pmed.1004141
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36580444
UR  - http://hdl.handle.net/10044/1/101900
VL  - 19
ER  -
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