Weather is an important short-term, local driver of population size and dispersal, which in turn contribute to patterns of genetic diversity and differentiation within species. Climate change is leading to greater weather variability and more frequent extreme weather events. While the effects of long-term and broad-scale mean climate conditions on genetic variation are well studied, our understanding of the effects of weather variability and extreme conditions on genetic variation is less developed. We assessed the influence of temperature and snow depth on genetic diversity and differentiation of populations of the alpine butterfly, Parnassius smintheus. We examined the relationships between a suite of variables, including those representing extreme conditions, and population-level genetic diversity and differentiation across 1453 single nucleotide polymorphisms, using both linear and gravity models. We additionally examined effects of land cover variables known to influence dispersal and gene flow in this species. We found that extreme low temperature events and the lowest recorded mean snow depth were significant predictors of genetic diversity. Extreme low temperature events, mean snow depth and land cover resistance were significant predictors of genetic differentiation. These results are congruent with known effects of early winter weather on population size and habitat connectivity on dispersal in P. smintheus. Our results demonstrate the potential for changes in the frequency or magnitude of extreme weather events to alter patterns of genetic diversity and differentiation.

Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual\'s genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response.

BACKGROUND: Rs768705 (TMEM161B) is one of the identified single nucleotide polymorphisms related to major depressive disorder (MDD). Paranoid personality traits are independently associated with the risk of MDD. This study aimed to investigate the interaction effect between rs768705 (TMEM161B) and paranoid personality traits on the new-onset risk of MDD in Chinese freshmen.
METHODS: A longitudinal study was conducted among 7642 Chinese freshmen without lifetime MDD at baseline in 2018. 158 new-onset MDD cases were ascertained in 2019. DNA samples were extracted to detect the genotype of rs768705. The diagnostic and statistical manual of mental disorders-IV criteria were used to determine MDD and personality disorder traits. Multiplicative interaction was assessed by logistic regression models. Tomas Andersson\'s method for calculating biological interactions was used to estimate the additive interaction.
RESULTS: Rs768705(AG) (OR = 1.88, 95 % CI: 1.24-2.83) and paranoid personality traits (OR = 3.68, 95 % CI: 2.57-5.26) were significantly associated with the risk of MDD. The multiplicative interaction model with the product term of rs768705 and paranoid personality trait traits had a significant interaction effect (OR = 4.20, 95 % CI:1.62-10.91). There was also a significant additive interaction effect (RR = 7.08, 95 % CI:4.31-11.65) for the incidence of MDD. Seventy seven percent patients among new MDD cases were attributed to the additive interaction effect between rs768705 and paranoid personality traits.
CONCLUSIONS: Rs768705 (AG) may interact with paranoid personality traits to increase the incidence of MDD among Chinese college students. Schools and psychosocial health organizations should pay more attention to individuals with paranoid personality traits for MDD intervention and prevention.

UNASSIGNED: The toxin-antitoxin (TA) system plays a vital role in the virulence and pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). However, the regulatory mechanisms and the impact of gene mutations on M. tuberculosis transmission remain poorly understood.
UNASSIGNED: To investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics.
UNASSIGNED: We performed whole-genome sequencing on the analyzed strains of M. tuberculosis. The genes associated with the toxin-antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Mutations correlating with enhanced transmission within the genes were identified by using random forest, gradient boosting decision tree, and generalized linear mixed models.
UNASSIGNED: A total of 13,518 M. tuberculosis isolates were analyzed, with 42.29% (n = 5,717) found to be part of genomic clusters. Lineage 4 accounted for the majority of isolates (n = 6488, 48%), followed by lineage 2 (n = 5133, 37.97%). 23 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, including vapB1 G34A, vapB24 A76C, vapB2 T171C, mazF2 C85T, mazE2 G104A, vapB31 T112C, relB T226A, vapB11 C54T, mazE5 T344C, vapB14 A29G, parE1 (C103T, C88T), and parD1 C134T. Six SNPs, including vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, Rv2653c A80C, and vapB22 C167T, were associated with transmission clades across different countries. Notably, our findings highlighted the positive association of vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, vapB19 C188T, and Rv2653c A80C with transmission clades across diverse regions. Furthermore, our analysis identified 32 SNPs that exhibited significant associations with clade size.
UNASSIGNED: Our study presents potential associations between mutations in genes related to the toxin-antitoxin system and the transmission dynamics of M. tuberculosis. However, it is important to acknowledge the presence of confounding factors and limitations in our study. Further research is required to establish causation and assess the functional significance of these mutations. These findings provide a foundation for future investigations and the formulation of strategies aimed at controlling TB transmission.

BACKGROUND: Chemokines and cytokines are components of the tumor microenvironment and also influence tumorigenesis and its composition. However, whether they genetically proxy tumorigenesis is unclear. For causal inferences, eQTL and pQTL were used to determine the role of chemokines and cytokines in pan-cancer. The impact on the tumor immune microenvironment was also explored.
METHODS: This study leveraged summary statistics from respective genome-wide association studies (GWAS) of 109 cytokines and chemokines in 18 types of solid tumors. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines and chemokines, located in or close to their coding gene (cis), were used as instrumental variables. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results. The impact on immune infiltration was investigated using the TIMER and TISIDB websites. Survival analysis was conducted using the K-M plotter and TIMER 2.0 websites. The TISCH and GEO databases were used to carry out scRNA cell analysis.Analyzing relevant proteins using the STRING database and conducting enrichment pathways for GO analysis of the identified proteins.
RESULTS: The results of the inverse-variance weighted (IVW) method using cis-protein QTL (cis-pQTL) instruments showed the causal effects of TNF in reducing the risk of squamous cell lung cancer (LUSC) and HGF in reducing the risk of head and neck cancer (HNSC).The results were consistent with the eQTL. HGF was associated with better overall survival (OS) in HNSC, regardless of the types of cells enriched. However, high expression of the ligand MET for HGF leads to a decrease in overall survival in LUSC. TNF was related to poor OS in LUSC with no significant impact. However, in CD8 + T cell-enriched, eosinophil-enriched, macrophage-enriched, and NK cell-deficient types of LUSC, high expression of TNF leads to a poor prognosis, and there is statistical significance. The results showed a significant positive correlation between TNF and most immune cell infiltration, immunomodulator and chemokine in LUSC. HGF is positively correlated with the majority of immune cells except CD56 + cells, as well as some immune regulatory factors and chemotactic factors. According to single-cell sequencing results, HGF is mainly secreted by fibroblasts and myofibroblasts in HNSC, while in LUSC, it is primarily secreted by macrophages and CD8 + T cells secrete TNF. The GO/KEGG analysis suggests that proteins related to HGF are mainly involved in regulating peptidyl-tyrosine phosphorylation and positive regulation of the MAPK cascade. Proteins related to TNF are primarily associated with the regulation of I-kappaB kinase/NF-kappaB signaling and cytokine-mediated signaling pathway.
CONCLUSIONS: HGF is primarily secreted by fibroblasts in HNSC and may have a protective effect on the occurrence and prognosis of HNSC. These effects are independent of immune cell influence, and this role may not necessarily be mediated through the HGF/MET pathway. On the other hand, TNF in LUSC is mainly secreted by immune cells like CD8 + T cell, and it may have a protective effect on the occurrence of LUSC. However, it\'s impact on the prognosis of LUSC through the immune microenvironment may have a different effect.
Chemokines and cytokines are not only components of the tumor microenvironment but also affect tumorigenesis and the composition of the tumor microenvironment. However, whether they genetically proxy tumorigenesis is unclear. For causal inferences, eQTL and pQTL were used to define the role of chemokines and cytokines in pan-cancer. The impact on the tumor immune microenvironment was also explored. This study leveraged the summary statistic from respective genome wide association study (GWAS) of 109 cytokines and chemokines to 18 types of solid tumor. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines and chemokines, located in or close to their coding gene (cis), were used as instrumental variables. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results. The results showed HGF is primarily secreted by fibroblasts in HNSC, and it may have a protective effect on the occurrence and prognosis of HNSC. These effects are independent of immune cell influence, and this role may not be mediated through the HGF/MET pathway. On the other hand, TNF in LUSC is mainly secreted by immune cells like CD8 + T cell, and it may have a protective effect on the occurrence of LUSC. However, it’s impact on the prognosis of LUSC through the immune microenvironment may have a different effect.

OBJECTIVE: Shortness of breath is a common symptom in patients with cancer. However, the mechanisms that underlie this troublesome symptom are poorly understood. Therefore, this study aimed to determine the prevalence of and associated risk factors for shortness of breath in women prior to breast cancer surgery and identify associations between shortness of breath and polymorphisms for potassium channel genes.
METHODS: Patients were recruited prior to breast cancer surgery and completed a self-report questionnaire on the occurrence of shortness of breath. Genotyping of single nucleotides polymorphism (SNPs) in potassium channel genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of shortness of breath and SNPs in ten candidate genes.
RESULTS: Of the 398 patients, 11.1% reported shortness of breath. These patients had a lower annual household income, a higher comorbidity burden, and a lower functional status. After controlling for functional status, comorbidity burden, genomic estimates of ancestry and self-reported race and ethnicity, the genetic associations that remained significant in the multiple regression analyses were for potassium voltage-gated channel subfamily D (KCND2) rs12673992, potassium voltage-gated channel modifier subfamily S (KCNS1) rs4499491, and potassium two pore channel subfamily K (KCNK2) rs4411107.
CONCLUSIONS: While these findings warrant replication, they suggest that alterations in potassium channel function may contribute to the occurrence of shortness of breath in women prior to breast cancer surgery.

G-quadruplex/thioflavin T (G4/THT) is one of the ideal label-free fluorescent light-emitting elements in the field of biosensors due to its good programmability and adaptability. However, the unsatisfactory luminous efficiency of single-molecule G4/THT limits its more practical applications. Here, we developed a G4 embedded semi-catalytic hairpin assembly (G4-SCHA) reaction by rationally modifying the traditional CHA reaction, and combined with the invasive reaction, supplemented by magnetic separation technology, for label-free sensitive detection of single nucleotide polymorphisms (SNPs). The invasive reaction enabled specific recognition of single-base mutations in DNA sequences as well as preliminary signal cycle amplification. Then, magnetic separation was used to shield the false positive signals. Finally, the G4-SCHA was created for secondary amplification and label-free output of the signal. This dual-signal amplified label-free biosensor has been shown to detect mutant targets as low as 78.54 fM. What\'s more, this biosensor could distinguish 0.01 % of the mutant targets from a mixed sample containing a large number of wild-type targets. In addition, the detection of real and complex biological samples also verified the practical application value of this biosensor in the field of molecular design breeding. Therefore, this study improves a label-free fluorescent light-emitting element, and then proposes a simple, efficient and universal label-free SNP biosensing strategy, which also provides an important reference for the development of other G4/THT based biosensors.

Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies.

Investigative leads are not generated by traditional forensic DNA testing, if the source of the forensic evidence or a 1st degree relative of unidentified human remains is not in the DNA database. In such cases, forensic genetic genealogy (FGG) can provide valuable leads. However, FGG generated genetic data contain private and sensitive information. Therefore, it is essential to deploy approaches that minimize unnecessary disclosure of these data to mitigate potential risks to individual privacy. We recommend protective practices that need not impact effective reporting of relationship identifications. Examples include performing one-to-one comparisons of DNA profiles of third-party samples and evidence samples offline with an \"air gap\" to the internet and shielding the specific shared single nucleotide polymorphisms (SNP) states and locations by binning adjacent SNPs in forensic reports. Such approaches reduce risk of unwanted access to or reverse engineering of third-party individuals\' genetic data and can give these donors greater confidence to support use of their DNA profiles in FGG investigation.
[Box: see text].

Preeclampsia or high blood pressure in pregnancy is one of the special disorders during pregnancy. It seems that oxidative stress plays an important role in the occurrence of this disease. The purpose of this study is to investigate the relationship between the A313G polymorphism in exon five of the glutathione S-transferase gene (GSTP1) and the risk of preeclampsia in a case-control study. In this study, blood samples were collected from 70 healthy pregnant women and 70 women with preeclampsia. After genomic DNA extraction, the PCR-RFLP method was performed to check the genotype in GSTP1-A313G and the genotypic frequencies of AA, AG, and GG were determined in all samples. Also, using bioinformatics software, the effect of the above polymorphism on the protein structure was investigated. Statistical analysis for A313G polymorphism showed that AG (OR: 1.1684, 95 % CI: 0.5877-2.3228, p = 0.657) and GG (OR: 1.3793, 95 % CI: 0.3376-5.6359, p = 0.654) genotypes were not associated with risk of preeclampsia in the population of northern Iran. However, bioinformatic analyzes have shown that this polymorphism does have a destructive effect on the protein structure. However, more studies with larger sample sizes are needed to draw firm conclusions.