Here we report on detailed three-dimensional maps revealing how brain structure is influenced by individual genetic differences. A genetic continuum was detected, in which brain structure was increasingly similar in subjects with increasing genetic affinity. Genetic factors significantly influenced cortical structure in Broca’s and Wernicke’s language areas, as well as frontal brain regions (r2 MZ > 0.8, p < 0.05). Preliminary correlations were performed suggesting that frontal gray matter differences may be linked to Spearman’s g, which measures successful test performance across multiple cognitive domains (p < 0.05). These genetic brain maps reveal how genes determine individual differences, and may shed light on the heritability of cognitive and linguistic skills, as well as genetic liability for diseases that affect the human cortex.
The degree to which genes and environment determine brain structure and function is of fundamental importance. Largescale neuroimaging and genetic studies are beginning to uncover normal and disease-specific patterns of gene and brain function in large human populations. Yet, little is known about the genetic control of human brain structure, and how much individual genotype accounts for the wide variations among individual brains. Recent reports show that many cognitive skills are surprisingly heritable, with strong genetic influences on IQ, verbal and spatial abilities, perceptual speed and even some personality qualities, including emotional reactions to stress. These genetic relationships persist even after statistical adjustments are made for shared family environments, which tend to make members of the same family more similar. Given that genetic and environmental factors, in utero and throughout lifetime, shape the physical development of the brain, we aimed to map patterns of brain structure that are under significant genetic control, and determine whether these structural features are linked with measurable differences in cognitive function. The few existing studies of brain structure in twins suggest that the overall volume of the brain itself and some brain structures, including the corpus callosum and ventricles, are somewhat genetically influenced, whereas gyral patterns, observed qualitatively or by comparing their twodimensional projections, are much less heritable. To make the transition from volumes of structures to detailed maps of genetic influences, advances in brain mapping technology have allowed the detailed mapping of structural features of the human cortex, including gray matter distribution, gyral patterning, and brain asymmetry. These features each vary with age, gender, handedness, hemispheric dominance and cognitive
performance in both health and disease. Composite maps of these features, generated for large populations, can reveal patterns not observable in an individual. Such patterns include statistical maps that show whether heredity and nongenetic factors are involved in determining specific aspects of brain structure.
Among the structural features that are genetically regulated and have implications for cortical function is the distribution of gray matter across the cortex. This varies widely across normal individuals, with developmental waves of gray matter gain and loss
subsiding by adulthood, and complex deficit patterns observed in Alzheimer’s disease, schizophrenia, and healthy subjects at genetic risk for these disorders. In this study, we began by comparing the average differences in gray matter (Fig. 1) in groups of unrelated subjects, dizygotic (DZ) and monozygotic (MZ) twins (see Methods). Although both types of twins share gestational and postgestational rearing environments, DZ twins share, on average, half their segregating genes, whereas MZ twins are normally genetically identical (with rare exceptions due to somatic mutations).
We found that brain structure is under significant genetic control, in a broad anatomical region that includes frontal and language-related cortices. The quantity of frontal gray matter, in particular, was most similar in individuals who were genetically alike; intriguingly, these individual differences in brain structure were tightly linked with individual differences in IQ (intelligence quotient). The resulting genetic brain maps reveal a strong relationship between genes, brain structure and behavior, suggesting
that highly heritable aspects of brain structure may be fundamental in determining individual differences in cognition. Read the rest of this entry »
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02 24th, 2008| 