title: Autism-associated promoter variant in MET impacts functional and structural brain networks.
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.
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA 90095-7085, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rudie
authors.forename: Leanna M
authors.initials: LM
authors.lastname: Hernandez
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Brown
authors.forename: Devora
authors.initials: D
authors.lastname: Beck-Pancer
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Colich
authors.forename: Philip
authors.initials: P
authors.lastname: Gorrindo
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Bookheimer
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
authors.forename: Mirella
authors.initials: M
authors.lastname: Dapretto
mesh_terms: D000293:Adolescent; D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D012307:Risk Factors
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met