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The joint analysis of imaging‐genetics data facilitates the systematic investigation of genetic effects on brain structures and functions with spatial specificity. We focus on voxel‐wise genome‐wide association analysis, which may involve trillions of single nucleotide polymorphism (SNP)‐voxel pairs. We attempt to identify underlying organized association patterns of SNP‐voxel pairs and understand the polygenic and pleiotropic networks on brain imaging traits. We propose abi‐cliquegraph structure (ie, a set of SNPs highly correlated with a cluster of voxels) for the systematic association pattern. Next, we develop computational strategies to detect latent SNP‐voxelbi‐cliquesand an inference model for statistical testing. We further provide theoretical results to guarantee the accuracy of our computational algorithms and statistical inference. We validate our method by extensive simulation studies, and then apply it to the whole genome genetic and voxel‐level white matter integrity data collected from 1052 participants of the human connectome project. The results demonstrate multiple genetic loci influencing white matter integrity measures on splenium and genu of the corpus callosum. 

Abstract Although digital health solutions are increasingly popular in clinical psychiatry, one application that has not been fully explored is the utilization of survey technology to monitor patients outside of the clinic. Supplementing routine care with digital information collected in the “clinical whitespace” between visits could improve care for patients with severe mental illness. This study evaluated the feasibility and validity of using online self-report questionnaires to supplement in-person clinical evaluations in persons with and without psychiatric diagnoses. We performed a rigorous in-person clinical diagnostic and assessment battery in 54 participants with schizophrenia (N = 23), depressive disorder (N = 14), and healthy controls (N = 17) using standard assessments for depressive and psychotic symptomatology. Participants were then asked to complete brief online assessments of depressive (Quick Inventory of Depressive Symptomatology) and psychotic (Community Assessment of Psychic Experiences) symptoms outside of the clinic for comparison with the ground-truth in-person assessments. We found that online self-report ratings of severity were significantly correlated with the clinical assessments for depression (two assessments used: R = 0.63, p < 0.001; R = 0.73, p < 0.001) and psychosis (R = 0.62, p < 0.001). Our results demonstrate the feasibility and validity of collecting psychiatric symptom ratings through online surveys. Surveillance of this kind may be especially useful in detecting acute mental health crises between patient visits and can generally contribute to more comprehensive psychiatric treatment. 

Abstract MotivationThe advancement of high-throughput technology characterizes a wide variety of epigenetic modifications and noncoding RNAs across the genome involved in disease pathogenesis via regulating gene expression. The high dimensionality of both epigenetic/noncoding RNA and gene expression data make it challenging to identify the important regulators of genes. Conducting univariate test for each possible regulator–gene pair is subject to serious multiple comparison burden, and direct application of regularization methods to select regulator–gene pairs is computationally infeasible. Applying fast screening to reduce dimension first before regularization is more efficient and stable than applying regularization methods alone. ResultsWe propose a novel screening method based on robust partial correlation to detect epigenetic and noncoding RNA regulators of gene expression over the whole genome, a problem that includes both high-dimensional predictors and high-dimensional responses. Compared to existing screening methods, our method is conceptually innovative that it reduces the dimension of both predictor and response, and screens at both node (regulators or genes) and edge (regulator–gene pairs) levels. We develop data-driven procedures to determine the conditional sets and the optimal screening threshold, and implement a fast iterative algorithm. Simulations and applications to long noncoding RNA and microRNA regulation in Kidney cancer and DNA methylation regulation in Glioblastoma Multiforme illustrate the validity and advantage of our method. Availability and implementationThe R package, related source codes and real datasets used in this article are provided at https://github.com/kehongjie/rPCor. Supplementary informationSupplementary data are available at Bioinformatics online.