When genes meet the brain Insights from imaging genetics into human complex traits

While the investigation into complex human traits has extended for over a century, the mechanisms underlying many of them remain poorly understood. Imaging genetics is an interdisciplinary field that integrates genetic and neuroimaging techniques to explore the influence of genetic variations on brain structure and function, subsequently impacting complex traits. This thesis aims to identify the neural mechanisms underlying complex traits within the framework of imaging genetics. First, a systematic exploration of genetic relationships between the brain and various traits revealed distinct associations between brain structure/function and genetic predispositions to mental health and cognition. Second, we established links between gene expression and the neural correlates of major depressive disorder and risky behaviors, suggesting the intermediary processes bridging genes and their associated brain patterns. Addressing concerns about the replicability of neuroimaging analyses, the third objective of the thesis was to assess the replicability of brain-phenotype associations across various traits within different domains, emphasizing that large-scale neuroimaging data are required for replicable brain–phenotype associations. These findings have yielded valuable insights into the neural mechanisms underpinning complex traits, offering robust evidence for the pivotal roles of the brain in the pathways from genotype to phenotype.