No effect of a common allelic variant in the reelin gene on intermediate phenotype measures of brain structure, brain function, and gene expression.
BACKGROUND
A recent genome-wide association study linked a common variant in RELN (rs7341475G) with risk for schizophrenia in women. In the largest neuroimaging intermediate phenotype study reported so far, we evaluated the effect of rs7341475 on an extended array of different neuroscientific measures.


METHODS
Brain structure was evaluated with voxel-based morphometry and diffusion tensor imaging. Brain function during working memory was examined with functional magnetic resonance imaging. The RELN expression was determined in postmortem brain tissue of the dorsolateral prefrontal cortex and hippocampus. A total of 736 datasets were examined (voxel-based morphometry: n = 230, diffusion tensor imaging: n = 93, functional magnetic resonance imaging: n = 308, RELN expression: n = 105).


RESULTS
Our analyses did not provide evidence for a significant main effect of gene or gene x sex interaction effect on any of the examined measures.


CONCLUSIONS
This study does not suggest a significant impact of rs7341475 on brain structure, function, and RELN expression, arguing that this single nucleotide polymorphism and others linked with it do not affect brain measures related to the biology of schizophrenia.
Tost
Heike
H
Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1379, USA.
Lipska
Barbara K
BK
Vakkalanka
Radhakrishna
R
Lemaitre
Herve
H
Callicott
Joseph H
JH
Mattay
Venkata S
VS
Kleinman
Joel E
JE
Marenco
Stefano
S
Weinberger
Daniel R
DR
D000328:Adult; D000483:Alleles; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases; D010100:Oxygen