Parkinson's disease (PD) is a neurodegenerative disorder with serious symptoms of which, are not clearly demonstrated at the beginning stages of the disease, making treatment challenging. Understanding the genetic causes of PD can be useful for determining its mechanisms and proposing treatments and preventive methods. For different populations with different genetic backgrounds and lifestyles, genome-wide association studies (GWASs) represent a crucial approach for genetic analysis. In this study, a robust and efficient GWAS without dimensionality reduction applied to evaluate heritability and genetic causes of PD in the German and US populations. The results show higher rate of PD heritability in the German population. Moreover, 25 significant SNPs have been determined, as well as five newly identified candidate genes associated with PD and some potential drug candidates. Analysis also reveals various long noncoding RNAs (lncRNAs), microRNAs and transcription-factor binding sites (TFBSs) with potential in the prevention and treatment of PD.

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Non–small cell lung cancer (NSCLC) is the most common subtype of lung cancer among smokers, nonsmokers, women, and young individuals. Tobacco smoking and different stages of the NSCLC have important roles in cancer evolution and require different treatments. Existence of poorly effective therapeutic options for the NSCLC brings special attention to targeted therapies by considering genetic alterations. In this study, we used RNA‐Seq data to compare expression levels of RefSeq genes and to find some genes with similar expression levels. We utilized the “Weighted Gene Co‐expression Network Analysis” method for three different datasets to create coexpressed genetic modules having relations with the smoking status and different stages of the NSCLC. Our results indicate seven important genetic modules having important associations with the smoking status and cancer stages. Based on investigated genetic modules and their biological explanation, we then identified 13 newly candidate genes and 7 novel transcription factors in association with the NSCLC, the smoking status, and cancer stages. We then examined those results using other datasets and explained our results biologically to illustrate some important genes in relation with the smoking status and metastatic stage of the NSCLC that can bring some crucial information about cancer evolution. Our genetic findings also can be used as some therapeutic targets for different clinical conditions of the NSCLC.

Understanding the genetic causes of neurodegenerative disease (ND) can be useful for their prevention and treatment. Among the genetic variations responsible for ND, heritable germline variants have been discovered in genome‐wide association studies (GWAS), and nonheritable somatic mutations have been discovered in sequencing projects. Distinguishing the important initiating genes in ND and comparing the importance of heritable and nonheritable genetic variants for treating ND are important challenges. In this study, we analysed GWAS results, somatic mutations and drug targets of ND from large databanks by performing directed network‐based analysis considering a randomised network hypothesis testing procedure. A disease‐associated biological network was created in the context of the functional interactome, and the nonrandom topological characteristics of directed‐edge classes were interpreted. Hierarchical network analysis indicated that drug targets tend to lie upstream of somatic mutations and germline variants. Furthermore, using directed path length information and biological explanations, we provide information on the most important genes in these created node classes and their associated drugs. Finally, we identified nine germline variants overlapping with drug targets for ND, seven somatic mutations close to drug targets from the hierarchical network analysis and six crucial genes in controlling other genes from the network analysis. Based on these findings, some drugs have been proposed for treating ND via drug repurposing. Our results provide new insights into the therapeutic actionability of GWAS results and somatic mutations for ND. The interesting properties of each node class and the existing relationships between them can broaden our knowledge of ND.

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