TY - JOUR T1 - Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8732 LP - 8745 DO - 10.1523/JNEUROSCI.5993-11.2012 VL - 32 IS - 25 AU - Ming-Chang Chiang AU - Marina Barysheva AU - Katie L. McMahon AU - Greig I. de Zubicaray AU - Kori Johnson AU - Grant W. Montgomery AU - Nicholas G. Martin AU - Arthur W. Toga AU - Margaret J. Wright AU - Paul Shapshak AU - Paul M. Thompson Y1 - 2012/06/20 UR - http://www.jneurosci.org/content/32/25/8732.abstract N2 - 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. ER -