Genetic influences on human brain structure: a review of brain imaging studies in twins

Abstract

Twin studies suggest that variation in human brain volume is genetically influenced. The genes involved in human brain volume variation are still largely unknown, but several candidate genes have been suggested. An overview of structural Magnetic Resonance (brain) Imaging studies in twins is presented, which focuses on the influence of genetic factors on variation in healthy human brain volume. Twin studies have shown that genetic effects varied regionally within the brain, with high heritabilities of frontal lobe volumes (90-95%), moderate estimates in the hippocampus (40-69%), and environmental factors influencing several medial brain areas. High heritability estimates of brain structures were revealed for regional amounts of gray matter (density) in medial frontal cortex, Heschl's gyrus, and postcentral gyrus. In addition, moderate to high heritabilities for densities of Broca's area, anterior cingulate, hippocampus, amygdala, gray matter of the parahippocampal gyrus, and white matter of the superior occipitofrontal fasciculus were reported. The high heritability for (global) brain volumes, including the intracranium, total brain, cerebral gray, and white matter, seems to be present throughout life. Estimates of genetic and environmental influences on age-related changes in brain structure in children and adults await further longitudinal twin-studies. For prefrontal cortex volume, white matter, and hippocampus volumes, a number of candidate genes have been identified, whereas for other brain areas, only a few or even a single candidate gene has been found so far. New techniques such as genome-wide scans may become helpful in the search for genes that are involved in the regulation of human brain volume throughout life.

Figure 1

Genetically influenced focal gray matter density brain areas. Heritability estimates of gray matter density in focal brain areas in healthy adult humans are shown for the significance level thresholded A‐map superimposed on axial and sagittal sections through the magnetic resonance image of the standardized reference brain (left) and for the complete A‐map (right). Data are based on a study in 258 monozygotic and dizygotic twin‐pairs and their siblings from 112 Dutch families. For genetic analyses, structural equation modeling and voxel‐based morphometry was used. (From Hulshoff Pol et al., J Neurosci 2006, 26, 10235–10242, © Society for Neuroscience, reproduced by permission.)

Figure 2

Genetically influenced focal white‐matter density brain areas superimposed on the histologically defined map of the superior occipitofrontal fascicle. Heritability of white‐matter density in focal brain areas in healthy adult humans is shown for the significance level thresholded A‐map superimposed on axial and sagittal sections in the left (Lt) and right (Rt) hemisphere through the magnetic resonance image of the standardized reference brain (left) and superimposed on the histologically defined map of the occipitofrontal superior fascicle (middle) (reproduced with kind permission of Drs. K. Zilles, K. Amunts and U. Burgel). The complete A‐maps are shown on the right. (From Hulshoff Pol et al., J Neurosci 2006, 26, 10235–10242, © Society for Neuroscience, reproduced by permission.)