Article (Scientific journals)
Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain.
Kochunov, Peter; Glahn, David C.; Nichols, Thomas E. et al.
2011In Frontiers in Neuroscience, 5, p. 120
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Keywords :
ADAM10; GWAS; QTL; RORA; WM integrity; cortical thickness; genetic correlation; imaging genetics
Abstract :
[en] OBJECTIVES: The thickness of the brain's cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. METHODS: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 +/- 13.2 years) recruited from 73 (9.7 +/- 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. RESULTS: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD >/= 3.0) QTLs were localized within chromosome 15q22-23. More detailed localization reported no significant association (p < 5.10(-5)) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p </= 10(-3)) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer's disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p < 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p < 0.05) but failed to show a significant correlation (p = 0.09) with FA. DISCUSSION: This study identified a novel, significant QTL at 15q22-23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM-FA values.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Neurosciences & behavior
Author, co-author :
Kochunov, Peter
Glahn, David C.
Nichols, Thomas E.
Winkler, Anderson ;  Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
Hong, Elliot L.
Holcomb, Henry H.
Stein, Jason L.
Thompson, Paul M.
Curran, Joanne E.
Carless, Melanie A.
Olvera, Rene L.
Johnson, Matthew P.
Cole, Shelley A.
Kochunov, Valeria
Kent, Jack
Blangero, John
More authors (6 more) Less
Language :
English
Title :
Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain.
Publication date :
2011
Journal title :
Frontiers in Neuroscience
ISSN :
1662-4548
eISSN :
1662-453X
Publisher :
Frontiers Media S.A., Switzerland
Volume :
5
Pages :
120
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 03 May 2017

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