Heritability of structural brain traits an endophenotype approach to deconstruct schizophrenia

Structural brain phenotypes are quantitative traits showing considerable variation in human populations. Quantitative structural brain abnormalities are also repeatedly reported in patients with psychiatric disorders such as schizophrenia. Studying the genetic and environmental causes of these differences might therefore highlight biological mechanisms underlying neuroanatomical phenotypes and directly result in the identification of risk factors for schizophrenia. Heritability estimates indicate a strong genetic component contributing to neuroanatomical phenotypes. Brain structure volumes have substantial heritability rates ranging from high (70-95%) for total brain volume, cerebellar, gray and white matter, and corpus callosum, to moderate (40-70%) determined for the hippocampus, the four lobes (frontal, temporal, occipital, and parietal lobe), temporal horn volume, brain parenchyma, white matter hyperintensity, and planum temporal asymmetry. Middle structures of the brain show high heritability scores for the deeper structures (ontogenetically earlier formed) and moderate heritability scores for the surface structures. Structures formed earlier in development show consistently higher heritability rates than brain structures formed later in development, for example, surface structures, which seem to be influenced by environmental factors. Even higher heritability reaching 0.99 for total brain volume are estimated in nonhuman primate (NHP) models employing inbred extended pedigree and highly uniform rearing conditions, reducing the effects of environmental factors. Applying highly heritable structural brain phenotypes may serve as an endophenotype for gene mapping studies and lead to identification of genes that are involved in the regulation of human brain volume and the biological mechanisms involved in the causal mechanisms of psychiatric disorders.