The relationship between genetic variation and gene expression in individual brain cell types and subtypes has remained elusive. Here, we generated single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of 424 individuals of advanced age; analyzing 1.5 million nuclear transcriptomes, we assessed the effect of genetic variants on RNA expression incis(cis-eQTL) for 7 cell types and 81 cell subtypes. This effort identified 10,004 eGenes at the cell type level and 8,138 eGenes at the cell subtype level. Many eGenes are only detected within cell subtypes. A new variant influencesAPOEexpression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer pathology, accounting for the effect ofAPOEε4, providing mechanistic insights into both pathologies. While eQTLs are readily detected, only aTMEM106Bvariant robustly affects the proportion of cell subtypes. Integration of these results with GWAS highlighted the targeted cell type and likely causal gene within susceptibility loci for Alzheimer's, Parkinson's, schizophrenia, and educational attainment.

Background: Depression is a common psychiatric illness and global public health problem. However, our limited understanding of the biological basis of depression has hindered the development of novel treatments and interventions. Methods: To identify new candidate genes for therapeutic development, we examined single-nucleus RNA sequencing (snucRNAseq) data from the dorsolateral prefrontal cortex (N=424) in relation to ante-mortem depressive symptoms. To complement these direct analyses, we also used genome-wide association study (GWAS) results for depression (N=500,199) along with genetic tools for inferring the expression of 22,159 genes in 7 cell types and 55 cell subtypes to perform transcriptome-wide association studies (TWAS) of depression followed by Mendelian randomization (MR). Results: Our single-nucleus TWAS analysis identified 71 causal genes in depression that have a role in specific neocortical cell subtypes; 59 of 71 genes were novel compared to previous studies. Depression TWAS genes showed a cell type specific pattern, with the greatest enrichment being in both excitatory and inhibitory neurons as well as astrocytes. Gene expression in different neuron subtypes have different directions of effect on depression risk. Compared to lower genetically correlated traits (e.g. body mass index) with depression, higher correlated traits (e.g., neuroticism) have more common TWAS genes with depression. In parallel, we performed differential gene expression analysis in relation to depression in 55 cortical cell subtypes, and we found that genes such as ANKRD36, MADD, TAOK3, SCAI and CHUK are associated with depression in specific cell subtypes. Conclusions: These two sets of analyses illustrate the utility of large snucRNAseq data to uncover both genes whose expression is altered in specific cell subtypes in the context of depression and to enhance the interpretation of well-powered GWAS so that we can prioritize specific susceptibility genes for further analysis and therapeutic development.

With the impact of the COVID‐19 epidemic, the demand for masked face recognition technology has increased. In the process of masked face recognition, some problems such as less feature information and poor robustness to the environment are obvious. The current masked face recognition model is not quantified enough for feature extraction, there are large errors for faces with high similarity, and the categories cannot be clustered during the detection process, resulting in poor classification of masks, which cannot be well adapted to changes in multiple environments. To solve current problems, this paper designs a new masked face recognition model, taking improved Single Shot Multibox Detector (SSD) model as a face detector, and replaces the input layer VGG16 of SSD with Deep Residual Network (ResNet) to increase the receptive field. In order to better adapt to the network, we adjust the convolution kernel size of ResNet. In addition, we fine‐tune the Xception network by designing a new fully connected layer, and reduce the training cycle. The weights of the three input samples including anchor, positive and negative are shared and clustered together with triplet network to improve recognition accuracy. Meanwhile, this paper adjusts alpha parameter in triplet loss. A higher value of alpha can improve the accuracy of model recognition. We further adopt a small trick to classify and predict face feature vectors using multi‐layer perceptron (MLP), and a total of 60 neural nodes are set in the three neural layers of MLP to get higher classification accuracy. Moreover, three datasets of MFDD, RMFRD and SMFRD are fused to obtain high‐quality images in different scenes, and we also add data augmentation and face alignment methods for processing, effectively reducing the interference of the external environment in the process of model recognition. According to the experimental results, the accuracy of masked face recognition reaches 98.3%, it achieves better results compared with other mainstream models. In addition, the hyper‐parameters tuning experiment is carried out to improve the utilization of computing resources, which shows better results than the indicators of different networks.