Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22500773
TITLE
Altered structural brain connectivity in healthy carriers of the autism risk gene, CNTNAP2.
ABSTRACT
Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower [corrected] eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.
DATE PUBLISHED
2011
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/04/17 06:00
pubmed 2011/01/01 00:00
medline 2013/01/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Dennis EL Dennis Emily L EL Laboratory of Neuro Imaging, Ahmanson Lovelace Brain Mapping Center, UCLA School of Medicine, Los Angeles, California 90095-7334, USA.
Jahanshad N Jahanshad Neda N
Rudie JD Rudie Jeffrey D JD
Brown JA Brown Jesse A JA
Johnson K Johnson Kori K
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Montgomery G Montgomery Grant G
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Bookheimer SY Bookheimer Susan Y SY
Dapretto M Dapretto Mirella M
Toga AW Toga Arthur W AW
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 1
ISSUE: 6
TITLE: Brain connectivity
ISOABBREVIATION: Brain Connect
YEAR: 2011
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2158-0022
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Brain Connect
COUNTRY: United States
ISSNLINKING:
NLMUNIQUEID: 101550313
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn Brain Connect. 2012;2(6):356 20176116
GRANTS
GRANTID AGENCY COUNTRY
EB007813 NIBIB NIH HHS United States
EB008281 NIBIB NIH HHS United States
P41 RR013642 NCRR NIH HHS United States
P41 RR013642 NCRR NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
T15 LM007356 NLM NIH HHS United States
T15 LM07356 NLM NIH HHS United States
T32 GM008042 NIGMS NIH HHS United States
U01 MH093765 NIMH NIH HHS United States
U01 MH093765 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Autistic Disorder physiopathology
Brain physiology
Diffusion Tensor Imaging methods
Diseases in Twins physiopathology
Female physiopathology
Heterozygote physiopathology
Humans physiopathology
Male physiopathology
Membrane Proteins genetics
Nerve Net physiology
Nerve Tissue Proteins genetics
Risk Factors genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CNTNAP2 protein, human
0 Membrane Proteins
0 Nerve Tissue Proteins
OTHER ID's
OTHERID SOURCE
NIHMS392946 NLM
PMC3420970 NLM