Heritability of lobar brain volumes in twins supports genetic models of cerebral laterality and handedness

Although the left and right human cerebral hemispheres differ both functionally and anatomically, little is known about the environmental or genetic factors that govern central nervous system asymmetry. Nevertheless, cerebral asymmetry is strongly correlated with handedness, and handedness does have a significant genetic component. To explore the relative contribution of environmental and genetic influences on cerebral asymmetry, we examined the volumes of left and right cerebral cortex in a large cohort of aging identical and fraternal twins and explored their relationship to handedness. Cerebral lobar volumes had a major genetic component, indicating that genes play a large role in changes in brain volume that occur with aging. Shared environment, which likely represents in utero events, had about twice the effect on the left hemisphere as on the right, consistent with less genetic control over the left hemisphere. To test the major genetic models of handedness and cerebral asymmetry, twin pairs were divided into those with two right handers and those with at least one left hander (nonright handers). Genetic factors contributed twice the influence to left and right cerebral hemispheric volumes in right-handed twin pairs, suggesting a large decrement in genetic control of cerebral volumes in the nonright-handed twin pairs. This loss of genetic determination of the left and right cerebral hemispheres in the nonright-handed twin pairs is consistent with models postulating a right-hand left-hemisphere-biasing genetic influence, a "right-shift" genotype that is lost in nonright handers, resulting in decreased cerebral asymmetry.