Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP

Ashley A. Scott-Van Zeeland, Brett S. Abrahams, Ana I. Alvarez-Retuerto, Lisa I. Sonnenblick, Jeffrey D. Rudie, Dara Ghahremani, Jeanette A. Mumford, Russell A. Poldrack, Mirella Dapretto, Daniel H. Geschwind, Susan Y. Bookheimer

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Genetic studies are rapidly identifying variants that shape risk for disorders of human cognition, but the question of how such variants predispose to neuropsychiatric disease remains. Noninvasive human brain imaging allows assessment of the brain in vivo, and the combination of genetics and imaging phenotypes remains one of the only ways to explore functional genotype-phenotype associations in human brain. Common variants in contactin-associated protein-like 2 (CNTNAP2), a neurexin superfamily member, have been associated with several allied neurodevelopmental disorders, including autism and specific language impairment, and CNTNAP2 is highly expressed in frontal lobe circuits in the developing human brain. Using functional neuroimaging, we have demonstrated a relationship between frontal lobar connectivity and common genetic variants in CNTNAP2. These data provide a mechanistic link between specific genetic risk for neurodevelopmental disorders and empirical data implicating dysfunction of long-range connections within the frontal lobe in autism. The convergence between genetic findings and cognitive-behavioral models of autism provides evidence that genetic variation at CNTNAP2 predisposes to diseases such as autism in part through modulation of frontal lobe connectivity.

Original languageEnglish (US)
Article number56ra80
JournalScience Translational Medicine
Volume2
Issue number56
DOIs
StatePublished - Nov 3 2010

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Contactins
Frontal Lobe
Autistic Disorder
Genes
Brain
Proteins
Cognition Disorders
Functional Neuroimaging
Genetic Association Studies
Neuroimaging
Language
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Scott-Van Zeeland, A. A., Abrahams, B. S., Alvarez-Retuerto, A. I., Sonnenblick, L. I., Rudie, J. D., Ghahremani, D., ... Bookheimer, S. Y. (2010). Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP. Science Translational Medicine, 2(56), [56ra80]. https://doi.org/10.1126/scitranslmed.3001344

Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP. / Scott-Van Zeeland, Ashley A.; Abrahams, Brett S.; Alvarez-Retuerto, Ana I.; Sonnenblick, Lisa I.; Rudie, Jeffrey D.; Ghahremani, Dara; Mumford, Jeanette A.; Poldrack, Russell A.; Dapretto, Mirella; Geschwind, Daniel H.; Bookheimer, Susan Y.

In: Science Translational Medicine, Vol. 2, No. 56, 56ra80, 03.11.2010.

Research output: Contribution to journalArticle

Scott-Van Zeeland, AA, Abrahams, BS, Alvarez-Retuerto, AI, Sonnenblick, LI, Rudie, JD, Ghahremani, D, Mumford, JA, Poldrack, RA, Dapretto, M, Geschwind, DH & Bookheimer, SY 2010, 'Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP', Science Translational Medicine, vol. 2, no. 56, 56ra80. https://doi.org/10.1126/scitranslmed.3001344
Scott-Van Zeeland AA, Abrahams BS, Alvarez-Retuerto AI, Sonnenblick LI, Rudie JD, Ghahremani D et al. Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP. Science Translational Medicine. 2010 Nov 3;2(56). 56ra80. https://doi.org/10.1126/scitranslmed.3001344
Scott-Van Zeeland, Ashley A. ; Abrahams, Brett S. ; Alvarez-Retuerto, Ana I. ; Sonnenblick, Lisa I. ; Rudie, Jeffrey D. ; Ghahremani, Dara ; Mumford, Jeanette A. ; Poldrack, Russell A. ; Dapretto, Mirella ; Geschwind, Daniel H. ; Bookheimer, Susan Y. / Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP. In: Science Translational Medicine. 2010 ; Vol. 2, No. 56.
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