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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jahanshad N,Kohannim O,Hibar DP,Stein JL,McMahon KL,de Zubicaray GI,Medland SE,Montgomery GW,Whitfield JB,Martin NG,Wright MJ,Toga AW,Thompson PMdoi
10.1073/pnas.1105543109subject
Has Abstractpub_date
2012-04-03 00:00:00pages
E851-9issue
14eissn
0027-8424issn
1091-6490pii
1105543109journal_volume
109pub_type
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