RT Journal Article
SR Electronic
T1 Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8732
OP 8745
DO 10.1523/JNEUROSCI.5993-11.2012
VO 32
IS 25
A1 Ming-Chang Chiang
A1 Marina Barysheva
A1 Katie L. McMahon
A1 Greig I. de Zubicaray
A1 Kori Johnson
A1 Grant W. Montgomery
A1 Nicholas G. Martin
A1 Arthur W. Toga
A1 Margaret J. Wright
A1 Paul Shapshak
A1 Paul M. Thompson
YR 2012
UL http://www.jneurosci.org/content/32/25/8732.abstract
AB 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.