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We report effects of age, age(2), sex and additive genetic factors on variability in gray matter thickness, surface area and white matter integrity in 1,010 subjects from the Genetics of Brain Structure and Function Study. Age was more strongly associated with gray matter thickness and fractional anisotropy of water diffusion in white matter tracts, while sex was more strongly associated with gray matter surface area. Widespread heritability of neuroanatomic traits was observed, suggesting that brain structure is under strong genetic control. Furthermore, our findings indicate that neuroimaging-based measurements of cerebral variability are sensitive to genetic mediation. Fundamental studies of genetic influence on the brain will help inform gene discovery initiatives in both clinical and normative samples.

It is now well established that regional indices of brain structure such as cortical thickness, surface area or grey matter volume exhibit spatially variable patterns of heritability. However, a recent study found these patterns to change with age during development, a result supported by gene expression studies. Changes in heritability have not been investigated in adulthood so far and could have important implications in the study of heritability and genetic correlations in the brain as well as in the discovery of specific genes explaining them. Herein, we tested for genotype by age (G ×A) interactions, an extension of genotype by environment interactions, through adulthood and healthy aging in 902 subjects from the Genetics of Brain Structure (GOBS) study. A "jackknife" based method for the analysis of stable cortical thickness clusters (JASC) and scale selection is also introduced. Although additive genetic variance remained constant throughout adulthood, we found evidence for incomplete pleiotropy across age in the cortical thickness of paralimbic and parieto-temporal areas. This suggests that different genetic factors account for cortical thickness heritability at different ages in these regions.