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
22723713
TITLE
Gene network effects on brain microstructure and intellectual performance identified in 472 twins.
ABSTRACT
A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess approximately one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here, we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their nontwin siblings (mean age: 23.7 ± 2.1 SD years; 193 male/279 female). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it computationally more tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus.
DATE PUBLISHED
2012 Jun 20
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/06/23 06:00
pubmed 2012/06/23 06:00
medline 2012/08/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Chiang MC Chiang Ming-Chang MC Department of Biomedical Engineering, National Yang-Ming University, Taipei, 112, Taiwan.
Barysheva M Barysheva Marina M
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Johnson K Johnson Kori K
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Toga AW Toga Arthur W AW
Wright MJ Wright Margaret J MJ
Shapshak P Shapshak Paul P
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME: 32
ISSUE: 25
TITLE: The Journal of neuroscience : the official journal of the Society for Neuroscience
ISOABBREVIATION: J. Neurosci.
YEAR: 2012
MONTH: Jun
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1529-2401
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Neurosci
COUNTRY: United States
ISSNLINKING: 0270-6474
NLMUNIQUEID: 8102140
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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GRANTS
GRANTID AGENCY COUNTRY
AG016570 NIA NIH HHS United States
EB01651 NIBIB NIH HHS United States
P50 AG016570 NIA NIH HHS United States
R01 AG040060 NIA 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
R21 EB001561 NIBIB NIH HHS United States
R21 RR019771 NCRR NIH HHS United States
RR019771 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Algorithms
Anisotropy
Brain ultrastructure
Chromosomes, Human ultrastructure
Diffusion Tensor Imaging ultrastructure
Female ultrastructure
Gene Regulatory Networks physiology
Genome-Wide Association Study physiology
Genotype physiology
Humans physiology
Image Processing, Computer-Assisted physiology
Intelligence physiology
Intelligence Tests physiology
Linkage Disequilibrium physiology
Male physiology
Polymorphism, Single Nucleotide physiology
Twins, Dizygotic physiology
Twins, Monozygotic physiology
Young Adult physiology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS388054 NLM
PMC3420968 NLM