Imperial College London
Professor Philippe Froguel

ProfessorPhilippeFroguel

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6520p.froguel

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E306Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilman:2019:10.1016/j.jhep.2019.05.032,
author = {Wilman, HR and Parisinos, CA and Atabaki-Pasdar, N and Kelly, M and Thomas, EL and Neubauer, S and IMI, DIRECT Consortium and Mahajan, A and Hingorani, AD and Patel, RS and Hemingway, H and Franks, PW and Bell, JD and Banerjee, R and Yaghootkar, H},
doi = {10.1016/j.jhep.2019.05.032},
journal = {Journal of Hepatology},
pages = {594--602},
title = {Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration},
url = {http://dx.doi.org/10.1016/j.jhep.2019.05.032},
volume = {71},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND & AIMS: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. METHODS: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n=1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. RESULTS: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p<5×10-8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. CONCLUSION: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. LAY SUMMARY: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart
AU  - Wilman,HR
AU  - Parisinos,CA
AU  - Atabaki-Pasdar,N
AU  - Kelly,M
AU  - Thomas,EL
AU  - Neubauer,S
AU  - IMI,DIRECT Consortium
AU  - Mahajan,A
AU  - Hingorani,AD
AU  - Patel,RS
AU  - Hemingway,H
AU  - Franks,PW
AU  - Bell,JD
AU  - Banerjee,R
AU  - Yaghootkar,H
DO  - 10.1016/j.jhep.2019.05.032
EP  - 602
PY  - 2019///
SN  - 0168-8278
SP  - 594
TI  - Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
T2  - Journal of Hepatology
UR  - http://dx.doi.org/10.1016/j.jhep.2019.05.032
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31226389
UR  - https://www.sciencedirect.com/science/article/pii/S0168827819303538?via%3Dihub
UR  - http://hdl.handle.net/10044/1/71798
VL  - 71
ER  -
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