Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22232660
TITLE
Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene.
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.
DATE PUBLISHED
2012 Apr 3
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/01/09
entrez 2012/01/11 06:00
pubmed 2012/01/11 06:00
medline 2012/05/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Jahanshad N Jahanshad Neda N Laboratory of NeuroImaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
Kohannim O Kohannim Omid O
Hibar DP Hibar Derrek P DP
Stein JL Stein Jason L JL
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Whitfield JB Whitfield John B JB
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Toga AW Toga Arthur W AW
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 109
ISSUE: 14
TITLE: Proceedings of the National Academy of Sciences of the United States of America
ISOABBREVIATION: Proc. Natl. Acad. Sci. U.S.A.
YEAR: 2012
MONTH: Apr
DAY: 3
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN:
ISSNTYPE:
MEDLINE JOURNAL
MEDLINETA: Proc Natl Acad Sci U S A
COUNTRY: United States
ISSNLINKING: 0027-8424
NLMUNIQUEID: 7505876
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
1F31MH087061 NIMH NIH HHS United States
F30 AG041681 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
T15 LM07356 NLM NIH HHS United States
T32 GM008042 NIGMS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Brain anatomy & histology
Female anatomy & histology
Histocompatibility Antigens Class I genetics
Humans genetics
Male genetics
Membrane Proteins genetics
Polymorphism, Genetic genetics
Reference Values genetics
Transferrin metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 HFE protein, human
0 Histocompatibility Antigens Class I
0 Membrane Proteins
0 Transferrin
OTHER ID's
OTHERID SOURCE
PMC3325658 NLM