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PMID: 22958829 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Neuron ·Vol. 75 ·No. 5 ·2012-09-06 ·Pages 904-15

Rudie JD, Hernandez LM, Brown JA, Beck-Pancer D, Colich NL, Gorrindo P, Thompson PM, Geschwind DH, Bookheimer SY, Levitt P, Dapretto M

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.

MeSH Terms
Adolescent Brain/abnormalities,metabolism,physiopathology Child Child Development Disorders, Pervasive/epidemiology,genetics,physiopathology Female Humans Male Nerve Net/abnormalities,metabolism,physiopathology Promoter Regions, Genetic/genetics Proto-Oncogene Proteins c-met/genetics Risk Factors
Chemicals
MET protein, human Proto-Oncogene Proteins c-met
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Rudie Jeffrey D
Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA 90095-7085, USA.
Hernandez Leanna M
Brown Jesse A
Beck-Pancer Devora
Colich Natalie L
Gorrindo Philip
Thompson Paul M
Geschwind Daniel H
Bookheimer Susan Y
Levitt Pat
Dapretto Mirella
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2012.07.010
Published
2012-09-06
Pages
904-15
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC3454529
Subset
IM
Grants
NCRR NIH HHS · RR00865 · United States
NINDS NIH HHS · T32 NS048004 · United States
NIMH NIH HHS · T32 MH073526-05 · United States
NICHD NIH HHS · P50 HD055784 · United States
NIMH NIH HHS · R01 MH067842 · United States
NICHD NIH HHS · R01 HD06528001 · United States
NCRR NIH HHS · RR13642 · United States
NIMH NIH HHS · T32 MH073526 · United States
NIGMS NIH HHS · T32 GM008044 · United States
NICHD NIH HHS · R01 HD065280 · United States
NIGMS NIH HHS · T32 GM008042 · United States
NIMH NIH HHS · 1R01 MH080759 · United States
NCRR NIH HHS · C06 RR012169 · United States
NCRR NIH HHS · M01 RR000865 · United States
NIMH NIH HHS · R01 MH080759 · United States
NCRR NIH HHS · P41 RR013642 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2012.07.010 PMC Full Text View journal details
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