Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Elsevier Science full text link Elsevier Science Free PMC article
Full text links

Actions

.2012 Sep 6;75(5):904-15.
doi: 10.1016/j.neuron.2012.07.010.

Autism-associated promoter variant in MET impacts functional and structural brain networks

Affiliations

Autism-associated promoter variant in MET impacts functional and structural brain networks

Jeffrey D Rudie et al. Neuron..

Abstract

As genes that confer increased risk for autism spectrum disorder (ASD) are identified, a crucial next step is to determine how these risk factors impact brain structure and function and contribute to disorder heterogeneity. With three converging lines of evidence, we show that a common, functional ASD risk variant in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key social brain circuitry in children and adolescents with and without ASD. MET risk genotype predicted atypical fMRI activation and deactivation patterns to social stimuli (i.e., emotional faces), as well as reduced functional and structural connectivity in temporo-parietal regions known to have high MET expression, particularly within the default mode network. Notably, these effects were more pronounced in individuals with ASD. These findings highlight how genetic stratification may reduce heterogeneity and help elucidate the biological basis of complex neuropsychiatric disorders such as ASD.

Copyright © 2012 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Functional MRI activation patterns to emotional faces inMET risk carriers. A) Within group whole-brain activation (orange) and deactivation (blue) maps for CC “risk” group, GG “non-risk” group, and between groups (risk>non-risk; purple). B) Averages and standard errors for functional activation parameter estimates from regions in risk>non-risk contrast for each genotype phenotype subgroup (Full-scale IQ and MRI scanner included as covariates in 2×3 ANOVA model). *p<0.05.
Figure 2
Figure 2
Reduced default mode network (DMN) functional connectivity inMET risk carriers. A) DMN connectivity within CC “risk” group, GG “non-risk” group, and between groups (risk>non-risk; purple). B) Averages and standard errors for functional connectivity between posterior cingulate seed and medial prefrontal and frontal orbital clusters from GG>CC contrast for each genotype phenotype subgroup (age and IQ included as covariates in 2×3 ANOVA). PCC = posterior cingulate cortex. *p<0.05, **p<0.01.
Figure 3
Figure 3
Reduced white matter integrity inMET risk carriers. A) Results of Tract-Based Spatial Statistics analysis comparing fractional anisotropy (FA) in GG “non-risk” group vs. CC “risk” group (p<0.05, corrected). B) Averages and standard errors for FA values in tracts from non-risk>risk contrast for each genotype phenotype subgroup (age and IQ included as covariates in 2×3 ANOVA). ***p<0.001.
Figure 4
Figure 4
Schematic depicting a strategy for addressing phenotypic heterogeneity (applicable across different disorders). The shading of the ovals indicates variability in a given phenotypic measure (e.g., brain connectivity). The green outline of the ovals indicates individuals with a clinical diagnosis (e.g., ASD) relative to typically developing controls (TD). Although group differences on a phenotypic measure may be detected between a clinical sample and matched controls, considerable overlap often exists (1). Stratifying individuals by neuroimaging endophenotypes independent of diagnosis reveals a continuum of phenotypes (2). Common risk variants (>5% of the population) for a disorder (e.g., MET rs1858830 C/G SNP) may impact brain circuitry and thus offer a means to stratify populations, particularly when these variants are functional in nature (3). Sample stratification by diagnosis and genotype allows for enhanced parsing of phenotypic heterogeneity (4), ultimately providing new insights on the neural mechanisms underlying psychiatric disorders.
See this image and copyright information in PMC

References

    1. Alexander AL, Lee JE, Lazar M, Boudos R, DuBray MB, Oakes TR, Miller JN, Lu J, Jeong EK, McMahon, et al. Diffusion tensor imaging of the corpus callosum in Autism. Neuroimage. 2007;34:61–73. - PubMed
    1. Anderson JS, Druzgal TJ, Froehlich A, Dubray MB, Lange N, Alexander AL, Abildskov T, Nielsen JA, Cariello AN, Cooperrider JR, et al. Decreased Interhemispheric Functional Connectivity in Autism. Cereb Cortex. 2010;21:1134–1146. - PMC - PubMed
    1. Anderson JS, Nielsen JA, Froehlich AL, Dubray MB, Druzgal TJ, Cariello AN, Cooperrider JR, Zielinski BA, Ravichandran C, Fletcher PT, et al. Functional connectivity magnetic resonance imaging classification of autism. Brain. 2011;134:3742–3754. - PMC - PubMed
    1. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta, et al. A genomewide scan for common alleles affecting risk for autism. Hum Mol Genet. 2010 - PMC - PubMed
    1. Ashwin E, Ashwin C, Rhydderch D, Howells J, Baron-Cohen S. Eagle-eyed visual acuity: an experimental investigation of enhanced perception in autism. Biol Psychiatry. 2009;65:17–21. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp