LAUSR

Psychiatric disorders are a group of mental disorders characterized by psychological or behavioral disabilities. Losing of the ability to work and assuming the extensive cost of long-term treatment, patients with psychiatric disorders are forced to support a heavy financial and medical burden. The growth and development of brain structures are dynamic, and different brain structures have major and specific functions to control behavior and performance. It has been demonstrated that the dysfunction of different brain structures involved in different psychiatric disorders is due to widespread alterations in the functional connectivity in the brain. Because of the dynamic alterations during brain growth and development, it is reasonable to infer that different psychiatric disorders are involved in the dysfunction of different brain structures at different life stages. Genetic factors display a strong component in the etiology of psychiatric disorders. Gene expression is regulated by heredity, and the integration of genome-wide association studies (GWASs) and gene expression profile datasets has become a hot topic in recent studies, providing new insights into the mechanism underlying complex diseases. Based on these, it is feasible to further investigate the mechanisms of complex diseases through integrating GWASs and expression profile datasets. However, there are few studies comparing GWASs and gene expression profile datasets with the consideration of different brain structures and developmental stages for psychiatric disorders. In this study, we explored the abnormal brain structures associated with different psychiatric disorders at different life stages, through a comparative analysis of brain structure-specific and age-specific gene expression profiles and GWAS datasets for psychiatric disorders (Supplementary materials). The mRNA expression profiles of 16 brain structures at 13 developmental stages were derived from BrainSpan (Atlas of the Developing Human Brain, http:// www.brainspan.org/). To ensure the sample sizes of gene expression profile analysis, the brain transcriptomes were divided into five age groups:\ 37 post-conceptional weeks (pcw), 0–3 years, 4–13 years, 14–25 years, and[ 25 years. Each age group had at least three samples for different brain structures analyzed in this study. For each brain structure, the limma package was used to compare the gene expression profiles of each age group with that of all remaining samples in the same brain structure. The brainspecific differentially-expressed gene sets can be viewed as the gene expression biomarkers of the corresponding brain structure at a certain stage. Specifically in this study, the top 10% of identified differentially-expressed genes were used to generate representative gene sets specific to a certain brain structure at a certain development stage. The latest GWAS datasets of five common psychiatric disorders were downloaded from the Psychiatric Genomics Consortium website (http://www.med.unc.edu/pgc/). Briefly, these GWAS datasets included 7,387 cases and 8,567 controls Xin Qi and Cuiyan Wu have contributed equally to this work.