Psoriasis is a genetically-regulated, T lymphocyte-mediated autoimmune skin disease that causes systemic damage, seriously affecting patient quality of life and survival. Psoriasis treatments, which aim to control the disease’s development, are greatly limited because its etiology and pathogenesis have not yet been fully elucidated. A large number of studies have demonstrated that immunogenetic elements are the most important factors responsible for psoriasis susceptibility. This paper delineates the immunogenetic mechanisms of psoriasis and provides useful information with regards to performing drug repositioning for the treatment of psoriasis.

Cumulative evidence has revealed the association between mitochondrial dysfunction and Alzheimer’s disease (AD). Because the number of mitochondrial genes is very limited, the mitochondrial pathogenesis of AD must involve certain nuclear genes. In this study, we employed systems genetic methods to identify mitochondrion-associated nuclear genes that may participate in the pathogenesis of AD. First, we performed a mitochondrial genome-wide association study (MiWAS, n = 809) to identify mitochondrial single-nucleotide polymorphisms (MT-SNPs) associated with AD. Then, epistasis analysis was performed to examine interacting SNPs between the mitochondrial and nuclear genomes. Weighted co-expression network analysis (WGCNA) was applied to transcriptomic data from the same sample (n = 743) to identify AD-related gene modules, which were further enriched by mitochondrion-associated genes. Using hub genes derived from these modules, random forest models were constructed to predict AD risk in four independent datasets (n = 743, n = 542, n = 161, and n = 540). In total, 9 potentially significant MT-SNPs and 14,340 nominally significant MT-nuclear interactive SNPs were identified for AD, which were validated by functional analysis. A total of 6 mitochondrion-related modules involved in AD pathogenesis were found by WGCNA, from which 91 hub genes were screened and used to build AD risk prediction models. For the four independent datasets, these models perform better than those derived from AD genes identified by genome-wide association studies (GWASs) or differential expression analysis (DeLong’s test, p < 0.05). Overall, through systems genetics analyses, mitochondrion-associated SNPs/genes with potential roles in AD pathogenesis were identified and preliminarily validated, illustrating the power of mitochondrial genetics in AD pathogenesis elucidation and risk prediction.

Over the course of human history, billions of people worldwide have been infected by various viruses. Despite rapid progress in the development of biomedical techniques, it is still a significant challenge to find promising new antiviral targets and drugs. In the past, antiviral drugs mainly targeted viral proteins when they were used as part of treatment strategies. Since the virus mutation rate is much faster than that of the host, such drugs feature drug resistance and narrow-spectrum antiviral problems. Therefore, the targeting of host molecules has gradually become an important area of research for the development of antiviral drugs. In recent years, rapid advances in high-throughput sequencing techniques have enabled numerous genetic studies (such as genome-wide association studies (GWAS), clustered regularly interspersed short palindromic repeats (CRISPR) screening, etc.) for human diseases, providing valuable genetic and evolutionary resources. Furthermore, it has been revealed that successful drug targets exhibit similar genetic and evolutionary features, which are of great value in identifying promising drug targets and discovering new drugs. Considering these developments, in this article the authors propose a host-targeted antiviral drug discovery strategy based on knowledge of genetics and evolution. We first comprehensively summarized the genetic, subcellular location, and evolutionary features of the human genes that have been successfully used as antiviral targets. Next, the summarized features were used to screen novel druggable antiviral targets and to find potential antiviral drugs, in an attempt to promote the discovery of new antiviral drugs.