Cracking the brain's genetic code.

In PNAS, Fjell et al. (1) reveal a remarkable connection between genetics and neuroscience—a new discovery that reveals how genes shape our path through life. Their article draws thought-provoking links between modern genetics and how our brains develop, and even how we age: They find unsuspected patterns in how our genetic code drives childhood development; these patterns may even explain why our brains decline in characteristic ways late in life. In their prior work (2–4), the authors discovered “modules” of genetic organization in the human brain: clusters of key brain systems, each shaped by a common genetic blueprint. With this new genetic map of the brain as a guide, Fjell et al. (1) now show how these genetic modules change in unique ways, as we progress through life, using brain scans collected from over 1,000 people aged 4–88 y. The ebb and flow of brain development and aging follow their new genetic blueprint. Each of their genetic modules has a distinct profile of development and aging, pointing to organized clusters or “communities” of brain regions with common genetic determination and common trajectories of aging. The results are remarkable, and shed light on some unresolved questions in neuroscience, which are outlined in this commentary. If their genetic findings hold up in additional samples, they point to more efficient ways to identify genes and pathways that influence brain development and aging, and causal mechanisms that drive our brains toward mental illness or protect us. The new findings are encouraging for large-scale “biobanking” initiatives, many of which are starting up worldwide. Several biobanking efforts seek to discover factors that help or harm the brain, and our risk for psychiatric illness. As explained below, the new findings point to a roadmap that may speed up discoveries in psychiatric genetics. To see why, we need to consider classical neuroscientific theories of brain development and aging, and how large-scale imaging projects have led us to question and revise them. During the past 20 y of research, a highly dynamic picture of brain development has emerged, perhaps more dynamic than was suspected before modern brain scanning with MRI. Based on classical neuroanatomic data, it had long been known that the brain develops in a characteristic sequence. However, neuroimaging revealed, perhaps surprisingly to many researchers, that the sequence of brain remodeling exhibits a “shifting” pattern of tissue growth and loss. These changes can be seen and measured in brain scans, well into the teenage years and young adulthood. One “evolutionary-developmental” hypothesis suggests