Gene network effects on brain microstructure and intellectual performance identified in 472 twins

Chiang, M. C., Barysheva, M., McMahon, K. L., de Zubicaray, G. I., Johnson, K., Montgomery, G. W., Martin, N. G., Toga, A. W., Wright, M. J., Shapshak, P., & Thompson, P. M. (2012) Gene network effects on brain microstructure and intellectual performance identified in 472 twins. The Journal of Neuroscience, 32(25), pp. 8732-8745.

View at publisher


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).Wecombined clustering with genome-wide scanning to find brain systems withcommongenetic determination.Wethen 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.

Impact and interest:

26 citations in Scopus
Search Google Scholar™
25 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 85701
Item Type: Journal Article
Refereed: Yes
DOI: 10.1523/JNEUROSCI.5993-11.2012
ISSN: 1529-2401
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 The Authors
Deposited On: 28 Sep 2015 06:49
Last Modified: 29 Sep 2015 03:35

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page