Imaging genomics: Mapping the influence of genetics on brain structure and function

The last two decades have seen tremendous advances in our understanding of human brain structure and function, particularly at the level of systems neuroscience where neuroimaging methods have led to better delineation of brain networks. Even more striking advances have been reported in molecular genetics research where the Human Genome Project has provided a rough draft of the human genome including the total number of genes and their chromosomal locations. Yet, despite significant progress in molecular genetics and in neuroimaging-based research, there has been relatively little integration of the two fields. Indeed, fewer than 50 peer-reviewed ‘‘imaging genomics’’ articles—manuscripts where genetic information was used to inform neuroimaging experiments—were published by December 2006. However, as shown in Figure 1, the annual publication rates for human functional and anatomic imaging studies including genetic data either for sample selection or for grouping has increased each year since the completion of the Human Genome Project in 2003. Since the assimilation of genetics information into neuroimaging methods promises to significantly improve our understanding of normal and pathologic brain function, this Special Issue of Human Brain Mapping is devoted to imaging genomics. We hope that the 11 articles in this Special Issue spur additional research by providing several novel findings and by reviewing our current state of understanding in imaging genomics research. In order for a trait to be a useful phenotype for studies in imaging genomics, it must be influenced by genetic factors (i.e., heritable). Several articles in this Special Issue document the heritability of brain anatomy, as indexed by structural MRI. Giedd and colleagues review their ongoing work applying structural equation modeling to pediatric brain morphometric data collected from 150 monozygotic and dizygotic healthy twin pairs [Giedd et al., 2007]. These data demonstrate that most brain morphometric measures are highly heritable and have minimal shared environmental effects in childhood. To complement the article by Giedd and colleagues, Kahn and coworkers review work documenting genetic influences on neuroanatomic measures in adults [Kahn et al., 2007]. Adult twin studies indicate that genetic effects vary across brain regions, with the highest heritabilities reported for frontal lobe volumes (90– 95%), moderate heritability for hippocampal volume (40– 69%), and environmental factors influencing medial brain areas. Together, these manuscripts leave little doubt that gross human neuroanatomy is strongly influenced by genetics across the life span, particularly in the neocortex. However, it is also quite likely that environmental factors are also important determinants of brain anatomy, particularly during key developmental periods. The Saguenay *Correspondence to: David C. Glahn, Department of Psychiatry and Research Imaging Center, University of Texas Health Science Center at San Antonio, Texas. E-mail: glan@uthscsa.edu