Imperial College London
Portrait Picture

Professor Martin Wilkins

Faculty of Medicine, National Heart & Lung Institute

Professor of Clinical Pharmacology
 
 
 
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Contact

 

+44 (0)20 3313 6101m.wilkins Website

 
 
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Assistant

 

Mrs Elizabeth O'Brien +44 (0)20 3313 6101

 
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Location

 

NIHR Imperial Clinical Research FacilityICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ulrich:2020:10.1183/13993003.01486-2019,
author = {Ulrich, A and Wharton, J and Thayer, T and Swietlik, E and Assad, T and Desai, A and Graf, S and Harbaum, L and Humbert, M and Morrell, N and Nichols, W and Soubrier, F and Southgate, L and Tregouet, D-A and Trembath, R and Brittain, E and Wilkins, M and Prokopenko, I and Rhodes, C},
doi = {10.1183/13993003.01486-2019},
journal = {European Respiratory Journal},
pages = {1--9},
title = {Mendelian randomization analysis of red cell distribution width in pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1183/13993003.01486-2019},
volume = {55},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary arterial hypertension (PAH) is a rare disease that leads to premature death from right heart failure. It is strongly associated with elevated red cell distribution width (RDW), a correlate of several iron status biomarkers. High RDW values can signal early stage iron deficiency or iron deficiency anaemia. This study investigated if elevated RDW is causally associated with PAH.A two-sample Mendelian randomization (MR) approach was applied to investigate whether genetic predisposition to higher levels of RDW increases the odds of developing PAH. Primary and secondary MR analyses were performed using all available genome-wide significant RDW variants (n = 179) and five genome-wide significant RDW variants that act via systemic iron status, respectively. We confirmed the observed association between RDW and PAH (OR = 1.90, 95% CI = 1.80 - 2.01) in a multi-centre case-control study (N cases = 642, N disease controls = 15,889). The primary MR analysis was adequately powered to detect a causal effect (OR) from between 1.25-1.52 or greater based on estimates reported in the RDW GWAS or from our own data. There was no evidence for a causal association between RDW and PAH in either the primary (ORcausal = 1.07, 95% CI = 0.92 – 1.24) or the secondary (ORcausal = 1.09, 95% CI = 0.77 – 1.54) MR analysis.The results suggest that at least some of the observed association of RDW with PAH is secondary to disease progression. Results of iron therapeutic trials in PAH should be interpreted with caution as any improvements observed may not be mechanistically linked to the development of PAH.Take home message – Mendelian randomization using genetic data from the largest-to-date pulmonary arterial hypertension (PAH) cohort do not support RDW or iron deficiency as a cause of PAH, which is important when interpreting iron replacement trials in this condition.
AU  - Ulrich,A
AU  - Wharton,J
AU  - Thayer,T
AU  - Swietlik,E
AU  - Assad,T
AU  - Desai,A
AU  - Graf,S
AU  - Harbaum,L
AU  - Humbert,M
AU  - Morrell,N
AU  - Nichols,W
AU  - Soubrier,F
AU  - Southgate,L
AU  - Tregouet,D-A
AU  - Trembath,R
AU  - Brittain,E
AU  - Wilkins,M
AU  - Prokopenko,I
AU  - Rhodes,C
DO  - 10.1183/13993003.01486-2019
EP  - 9
PY  - 2020///
SN  - 0903-1936
SP  - 1
TI  - Mendelian randomization analysis of red cell distribution width in pulmonary arterial hypertension
T2  - European Respiratory Journal
UR  - http://dx.doi.org/10.1183/13993003.01486-2019
UR  - https://erj.ersjournals.com/content/55/2/1901486.article-info
UR  - http://hdl.handle.net/10044/1/74331
VL  - 55
ER  -
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