Imperial College London
Alternate

ProfessorJimmyBell

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3506 4608jimmy.bell Website

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sorokin:2022:10.1016/j.ajhg.2022.04.013,
author = {Sorokin, E and Basty, N and Whitcher, B and Liu, Y and Bell, JD and Cohen, R and Cule, M and Thomas, L},
doi = {10.1016/j.ajhg.2022.04.013},
journal = {American Journal of Human Genetics},
pages = {1092--1104},
title = {Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology},
url = {http://dx.doi.org/10.1016/j.ajhg.2022.04.013},
volume = {109},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank using magnetic resonance imaging, and provide the first reference range for spleen iron in an unselected population. Through genome-wide association study, we identify associations between spleen iron and regulatory variation at two hereditary spherocytosis genes, ANK1 and SPTA1 . Spherocytosis-causing coding mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while these novel common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes that have been observed clinically. Our genetic study also identifies a signal which co-localizes with a splicing quantitative trait locus for MS4A7 , and we show this gene is abundantly expressed in the spleen and in macrophages. The combination of deep learning and efficient image processing enables non-invasive measurement of spleen iron and, in turn, characterization of genetic factors related to iron recycling and erythrocyte morphology.
AU  - Sorokin,E
AU  - Basty,N
AU  - Whitcher,B
AU  - Liu,Y
AU  - Bell,JD
AU  - Cohen,R
AU  - Cule,M
AU  - Thomas,L
DO  - 10.1016/j.ajhg.2022.04.013
EP  - 1104
PY  - 2022///
SN  - 0002-9297
SP  - 1092
TI  - Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology
T2  - American Journal of Human Genetics
UR  - http://dx.doi.org/10.1016/j.ajhg.2022.04.013
UR  - http://hdl.handle.net/10044/1/99000
VL  - 109
ER  -
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