Brain Mapping Reveals How Genes Affect Human Brain Structure:

Background.                           Despite large-scale efforts to map genetic and brain variations in human populations, there have been no technologies available to link these two types of information. In response to this challenge, an international team of scientists designed a brain mapping strategy to create the first maps of genetic influences on human brain structure. The findings, published in the December issue of the journal Nature Neuroscience, offer exciting new insight into how brain diseases are passed on in families, and how individuals inherit personality traits and cognitive abilities.

Advance.          Using a database of MRI scans from the Finnish twin registry, the scientists developed a novel supercomputing approach to encode how brain structure varied between identical and fraternal pairs of twins. Qualities under genetic control show a characteristic pattern of varying hardly at all between identical twins, who have the same genes; quite a lot between fraternal twins, who share about half their genes; and a great deal between unrelated individuals. High-performance computing technology was developed to build three-dimensional maps of each subject's brain, and then to color code the degree of heritability for each brain region. The quantity of gray matter in the frontal lobes was under particularly tight genetic control, and was linked with individual intelligence (IQ), as was a region at the side of the left hemisphere known as Wernicke's area, which is central to language. The study showed that the more closely related two people are, the more likely they are to share similar brain structure in regions heavily controlled by genetics, such as the frontal cortex and language regions. They are also more likely to share vulnerabilities to specific diseases affecting these areas.

Implications.   This is the first study to create maps showing how strongly brain structure is determined by genes and inheritance. It also provides a technology to uncover how genes affect brain structure in thousands of subjects. The mapping strategy sheds light on the ‘nature/nurture’ debate, and is now being used to identify genetic and non-genetic triggers in diseases such as schizophrenia and dementia. Finding which structures are under greatest genetic control provides keys to where to look for degeneration in family members at risk for disease. The new maps pinpoint the areas at risk, allowing the team to examine differences in genetic profiles among family members, some of whom have a language or frontal cortex disorder--including schizophrenia and frontotemporal dementia--and others who do not. The scientists are applying the new brain mapping method in a several international projects to screen individuals at genetic risk for schizophrenia and Alzheimer's disease for early brain changes.

(A.W.. Toga)