Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene

Jahanshad, Neda, Kohannim, Omid, Hibar, Derrek P., Stein, Jason L., McMahon, Katie L., de Zubicaray, Greig I., Medland, Sarah E., Montgomery, Grant W., Whitfield, John B., Martin, Nicholas G., Wright, Margaret J., Toga, Arthur W. and Thompson, Paul M. (2012) Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. Proceedings of the National Academy of Sciences of USA, 109 14: E851-E859.

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Author Jahanshad, Neda
Kohannim, Omid
Hibar, Derrek P.
Stein, Jason L.
McMahon, Katie L.
de Zubicaray, Greig I.
Medland, Sarah E.
Montgomery, Grant W.
Whitfield, John B.
Martin, Nicholas G.
Wright, Margaret J.
Toga, Arthur W.
Thompson, Paul M.
Title Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene
Formatted title Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene
Journal name Proceedings of the National Academy of Sciences of USA  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2012-04-03
Sub-type Article
DOI 10.1073/pnas.1105543109
Volume number 109
Issue number 14
ISSN 0027-8424; 1091-6490
Start page E851
End page E859
Total pages 9
Place of publication Washington, DC, U.S.A.
Publisher National Academy of Sciences
Collection year 2013
Language eng
Formatted abstract Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.
Keyword Neuroimaging genetics
Twin modeling
Pathway analysis
Tensor-based morphometry
Voxel based analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under "PNAS Plus: Biological Sciences - Neuroscience - Social Sciences - Psychological and Cognitive Sciences".

 
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Created: Tue, 10 Jan 2012, 11:51:23 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging