Editors' ChoiceNeuroscience

The Big Picture

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Science Translational Medicine  04 Jul 2012:
Vol. 4, Issue 141, pp. 141ec117
DOI: 10.1126/scitranslmed.3004530

Although the brain is the most genetically determined organ of the human body, we have yet to identify which genes—or combinations thereof—influence the integrity, connectivity, and function of the brain. Indeed, the complexity of the brain has limited studies in this area because of the sheer number of statistical tests that would be needed to find a meaningful association: There are ~1 million genetic variants in the brain that likely interact with one another. Chiang et al. sought to examine these relationships by applying a novel approach to discover which genes contribute to brain wiring at all pairs of points in a brain scan.

Using in vivo neuroimaging and a novel statistical approach, Chiang and colleagues combined clustering with genome-wide scanning to determine genetic correlations between thousands of points in human brain images. They examined 472 twins and their nontwin siblings and found that the brain is designed to promote efficient interactions between genes and that its networks are resilient to potential damage from injury. In addition, those genes’ variants that reside at the hubs of brain networks influence intellectual performance by influencing the relations between performance IQ and the integrity of major white matter tracts.

Although this study has identified genetic networks that are crucial for normal brain functioning, the study cohort—a sample of Australian twins genotyped for a larger project designed to identify melanoma risk factors—may limit immediate generalizability. Future studies conducted in broader U.S. cohorts could address this issue. Research of this kind might advance knowledge about the biological underpinnings of brain function and empower work in imaging genomics that will clarify the interface between the brain, genes, and intellectual functioning.

M.-C. Chiang et al., Gene network effects on brain microstructure and intellectual performance identified in 472 twins. J. Neurosci. 32, 8732–8745 (2012). [Abstract]

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