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An understanding of human brain individuality requires the integration of data on brain organization across people and brain regions, molecular and systems scales, as well as healthy and clinical states. Here, we help advance this understanding by leveraging methods from computational genomics to integrate large-scale genomic, transcriptomic, neuroimaging, and electronic-health record data sets. We estimated genetically regulated gene expression (gr-expression) of 18,647 genes, across 10 cortical and subcortical regions of 45,549 people from the UK Biobank. First, we showed that patterns of estimated gr-expression reflect known genetic–ancestry relationships, regional identities, as well as inter-regional correlation structure of directly assayed gene expression. Second, we performed transcriptome-wide association studies (TWAS) to discover 1,065 associations between individual variation in gr-expression and gray-matter volumes across people and brain regions. We benchmarked these associations against results from genome-wide association studies (GWAS) of the same sample and found hundreds of novel associations relative to these GWAS. Third, we integrated our results with clinical associations of gr-expression from the Vanderbilt Biobank. This integration allowed us to link genes, via gr-expression, to neuroimaging and clinical phenotypes. Fourth, we identified associations of polygenic gr-expression with structural and functional MRI phenotypes in the Human Connectome Project (HCP), a small neuroimaging-genomic data set with high-quality functional imaging data. Finally, we showed that estimates of gr-expression and magnitudes of TWAS were generally replicable and that thep-values of TWAS were replicable in large samples. Collectively, our results provide a powerful new resource for integrating gr-expression with population genetics of brain organization and disease. 

Abstract Under nitrogen starvation, most legume plants form a nitrogen-fixing symbiosis with Rhizobium bacteria. The bacteria induce the formation of a novel organ called the nodule in which rhizobia reside as intracellular symbionts and convert atmospheric nitrogen into ammonia. During this symbiosis, miRNAs are essential for coordinating the various plant processes required for nodule formation and function. miRNAs are non-coding, endogenous RNA molecules, typically 20–24 nucleotides long, that negatively regulate the expression of their target mRNAs. Some miRNAs can move systemically within plant tissues through the vascular system, which mediates, for example, communication between the stem/leaf tissues and the roots. In this review, we summarize the growing number of miRNAs that function during legume nodulation focusing on two model legumes, Lotus japonicus and Medicago truncatula, and two important legume crops, soybean (Glycine max) and common bean (Phaseolus vulgaris). This regulation impacts a variety of physiological processes including hormone signaling and spatial regulation of gene expression. The role of mobile miRNAs in regulating legume nodule number is also highlighted.