Genetic Data Research Articles

Calafate (Berberis microphylla G. Forst) Populations from Chilean Patagonia Exhibit Similar Structuring at the Genetic and Metabolic Levels

Berberis microphylla, commonly known as calafate, is one of the most promising species of Chilean Patagonia to be domesticated, due to its anthocyanin-rich berries. The main aim of this study was to understand the genetic structure of the wild populations of B. microphylla in the main regions where it grows and its relationship with phenolic secondary metabolite profiles. Ripe berry samples and leaves were collected from the Aysén and Magallanes regions. Genetic analyses were carried out using 18 microsatellite markers. Phenolic compounds were extracted from the ripe fruits and were quantified using high-performance liquid chromatography (HPLC). Their antioxidant capacity was determined according to the Trolox equivalent antioxidant capacity (TEAC) assay. Total phenols were measured as their absorbance at a wavelength of 280 nm. Both the genetic and chemometric data were explored using unsupervised and supervised methods. The genetic markers suggest the existence of three groups, two of them corresponding to the Aysén and Magallanes samples, and the third corresponding to Chile Chico (a district in Aysén), which was the most divergent of the three. Similar results were observed in the phenolic profile obtained with chemometric analysis, with the same samples forming a separate third group. The differentiation achieved using the genetic and chemical data may be the result of intrinsic genetic differences, environmental effects on fruit maturity, or the sum of both factors. These are all points to consider in the domestication of this valuable species by selecting individuals with desirable traits and contrasting phenotypes.

The long‐beaked common dolphin of the eastern Pacific Ocean: Taxonomic status and redescription of Delphinus bairdii

AbstractNeritic, long‐beaked common dolphins have been described as species distinct from the more oceanic and globally distributed short‐beaked species, Delphinus delphis, although recent molecular studies have challenged this view. In the eastern North Pacific (ENP), the taxonomic status of the long‐beaked (bairdii) form has been controversial since its original description in 1873, and has vacillated between species, subspecies, and geographic forms several times. It is currently provisionally viewed as a subspecies of Delphinus delphis, D. d. bairdii. To clarify this situation, we reviewed the literature and conducted additional analyses using both newly obtained genetic and cranial morphometric data sets. The results indicate that there are diagnostic differences in skull morphology and coloration between the eastern Pacific long‐and short‐beaked forms, and near‐perfect diagnosability in mitochondrial DNA. These differences, along with indications of ecological distinctions, including important differences in life history parameters and reproductive timing, indicate that these forms are well on their way down separate evolutionary pathways. As such, we consider them to be distinct species in the eastern Pacific. The long‐beaked species is referable to Delphinus bairdii Dall, 1873, and is redescribed as such herein.

Genetic-based patient stratification in Alzheimer’s disease

Alzheimer's disease (AD) shows a high pathological and symptomatological heterogeneity. To study this heterogeneity, we have developed a patient stratification technique based on one of the most significant risk factors for the development of AD: genetics. We addressed this challenge by including network biology concepts, mapping genetic variants data into a brain-specific protein–protein interaction (PPI) network, and obtaining individualized PPI scores that we then used as input for a clustering technique. We then phenotyped each obtained cluster regarding genetics, sociodemographics, biomarkers, fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, and neurocognitive assessments. We found three clusters defined mainly by genetic variants found in MAPT, APP, and APOE, considering known variants associated with AD and other neurodegenerative disease genetic architectures. Profiling of these clusters revealed minimal variation in AD symptoms and pathology, suggesting different biological mechanisms may activate the neurodegeneration and pathobiological patterns behind AD and result in similar clinical and pathological presentations, even a shared disease diagnosis. Lastly, our research highlighted MAPT, APP, and APOE as key genes where these genetic distinctions manifest, suggesting them as potential targets for personalized drug development strategies to address each AD subgroup individually.

Unveiling blood pressure‐associated genes in aortic cells through integrative analysis of GWAS and RNA modification‐associated variants

AbstractBackgroundGenome‐wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell‐type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification‐associated single‐nucleotide polymorphisms (RNAm‐SNPs).MethodsUtilizing large‐scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm‐SNPs and BP. The association between RNAm‐SNPs, gene expression, and BP were examined.ResultsA total of 355 RNAm‐SNPs related to m6A, m1A, m5C, m7G, and A‐to‐I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m6A‐SNPs, highlighting the potential functional relevance of m6A in physiological processes influencing BP. Notably, m6A‐SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO‐overexpression and METTL14‐knockdown vascular smooth muscle cells were detected. RNAm‐SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA‐seq study, we identified ARID5A, HLA‐DPB1, HLA‐DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells.ConclusionThe present study identified RNAm‐SNPs in BP loci and elucidated the associations between the RNAm‐SNPs, gene expression, and BP. The identified BP‐associated genes in aortic cells were associated with AD.

A phylogenomic approach to a taxonomic revision: a combination, new synonymies, and a description of two new species within the camel spider genus Chanbria Muma, 1951 (Solifugae: Eremobatidae)

Abstract This study summarizes the taxonomic treatment of the camel spider genus Chanbria Muma, 1951. Taking an integrative taxonomic approach incorporating phylogenomic, morphological, and geographical information, the genus is herein revised. Of the four species currently placed in the genus, two are retained: Chanbria regalis Muma, 1951 and Chanbria serpentinus Muma, 1951. Eremochelis plicatus (Muma, 1962) is transferred to this genus because it is consistently recovered in a clade with Chanbria based on several phylogenetic analyses using hundreds of loci recovered from ultraconserved element data. In this study, we re-analyse previously acquired genomic data to assess former species hypotheses and identify new morphological synapomorphies that support the monophyly of Chanbria. The genetic data support the synonymization of Chanbria rectus Muma, 1962 syn. nov. with C. regalis. Furthermore, we synonymize Chanbria tehachapianus Muma, 1962 syn. nov. with C. regalis because C. tehachapianus was erected based on limited morphological information and lack of geographical separation between other populations of C. regalis. Two new species, Chanbria brookharti sp. nov. and Chanbria mapemes sp. nov., are described. This brings the total number of species of Chanbria described to five recognized species: C. regalis, C. serpentinus, C. plicatus com. nov., C. brookharti sp. nov., and C. mapemes sp. nov.

Drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as strategies for reducing cardiovascular disease risk

Abstract Background and Aims APOC3, ANGPTL3, and ANGPTL4 are circulating proteins that are actively pursued as pharmacological targets to treat dyslipidemia and reduce the risk of atherosclerotic cardiovascular disease. Here, we used human genetic data to compare the predicted therapeutic and adverse effects of APOC3, ANGPTL3, and ANGPTL4 inactivation. Methods We conducted drug-target Mendelian randomization analyses using variants in proximity to the genes associated with circulating protein levels to compare APOC3, ANGPTL3, and ANGPTL4 as drug targets. We obtained exposure and outcome data from large-scale genome-wide association studies and used generalized least squares to correct for linkage disequilibrium-related correlation. We evaluated five primary cardiometabolic endpoints and screened for potential side effects across 694 disease-related endpoints, 43 clinical laboratory tests, and 11 internal organ MRI measurements. Results Genetically lowering circulating ANGPTL4 levels reduced the odds of coronary artery disease (CAD) (odds ratio, 0.57 per s.d. protein [95%CI,0.47–0.70]) and type 2 diabetes (T2D) (odds ratio, 0.73 per s.d. protein [95%CI,0.57–0.94]). Genetically lowering circulating APOC3 levels also reduced the odds of CAD (odds ratio, 0.90 per s.d. protein [95%CI,0.82–0.99]). Genetically lowered ANGPTL3 levels via common variants were not associated with CAD. However, meta-analysis of deleterious variants revealed that ANGPTL3 inactivation protected against CAD (odds ratio, 0.79 per allele [95%CI, 0.69–0.90]). Analysis of lowered ANGPTL3, ANGPTL4, and APOC3 levels did not identify important safety concerns. Conclusion Human genetic evidence suggests that therapies aimed at reducing circulating levels of ANGPTL3, ANGPTL4, and APOC3 reduce the risk of CAD. ANGPTL4 lowering may also reduce the risk of T2D.

Comprehensive genomic profiling of salivary gland carcinoma: Analysis of the Center for Cancer Genomics and Advanced Therapeutics database in Japan.

Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C-CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC.

Variants in structural cardiac genes in patients with cancer therapy-related cardiac dysfunction after anthracycline chemotherapy: a case control study

BackgroundVariants in cardiomyopathy genes have been identified in patients with cancer therapy-related cardiac dysfunction (CTRCD), suggesting a genetic predisposition for the development of CTRCD. The diagnostic yield of genetic testing in a CTRCD population compared to a cardiomyopathy patient cohort is not yet known and information on which genes should be assessed in this population is lacking.MethodsWe retrospectively included 46 cancer patients with a history of anthracycline induced CTRCD (defined as a decrease in left ventricular ejection fraction (LVEF) to < 50% and a ≥ 10% reduction from baseline by echocardiography). Genetic testing was performed for 59 established cardiomyopathy genes. Only variants of uncertain significance and (likely) pathogenic variants were included. Diagnostic yield of genetic testing was compared with a matched cohort of patients with dilated cardiomyopathy (DCM, n = 46) and a matched cohort of patients without cardiac disease (n = 111).ResultsAverage LVEF at time of CTRCD diagnosis was 30.1 ± 11.0%. Patients were 52.9 ± 14.6 years old at time of diagnosis and 30 (65.2%) were female. Most patients were treated for breast cancer or lymphoma, with a median doxorubicin equivalent dose of 300 mg/m2 [112.5-540.0]. A genetic variant, either pathogenic, likely pathogenic or of uncertain significance, was identified in 29/46 (63.0%) of patients with CTRCD, which is similar to the DCM cohort (34/46, 73.9%, p = 0.262), but significantly higher than in the negative control cohort (47/111, 39.6%, p = 0.018). Variants in TTN were the most prevalent in the CTRCD cohort (43% of all variants). All (likely) pathogenic variants identified in the CTRCD cohort were truncating variants in TTN.There were no significant differences in severity of CTRCD and in recovery rate in variant-harbouring individuals versus non-variant harbouring individuals.ConclusionsIn this case-control study, cancer patients with anthracycline-induced CTRCD have an increased burden of genetic variants in cardiomyopathy genes, similar to a DCM cohort. If validated in larger prospective studies, integration of genetic data in risk prediction models for CTRCD may guide cancer treatment. Moreover, genetic results have important clinical impact, both for the patient in the setting of precision medicine, as for the family members that will receive genetic counselling.

Bat diversity in the Cuc Phuong National Park, Vietnam - Results from VIETBIO field training and annotated species list.

Biodiversity surveys are essential for both academic research and conservation. Integrative approaches that combine morphological, genetic and acoustic aspects for species identification can provide reliable information in taxonomy and evolution. This is especially relevant for those groups with a high degree of cryptic diversity such as bats. Here, we present the results from a field survey carried out in the Cuc Phuong National Park (CPNP) during 2019 as part of the VIETBIO project and from the examination of specimen collections preserved at the museums of CPNP and the Institute of Ecology and Biological Resources (IEBR). In addition, we include an annotated species list, based on this survey and a literature review. We here confirm that CPNP is home to at least 47 bat species belonging to 23 genera and seven families. We recorded ten of these bat species during our field survey. Obtained data in genetics (sequencing a fragment of the mitochondrial gene COI) supported the morphological identification of the recorded species for which we were able to produce these data. In addition, we include echolocation recordings obtained during our field training with the hope that they may contribute valuable insights to future work concerning the surveyed species. Results from the field survey represent a relevant contribution to biodiversity assessment efforts and, thus, support conservation and management efforts to maintain bat diversity in Vietnam.

Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study.

Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined. In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis. After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma. Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Synthesizing environmental, epidemiological and vector and parasite genetic data to assist decision making for disease elimination.

We present a framework for identifying when conditions are favourable for transmission of vector-borne diseases between communities by incorporating predicted disease prevalence mapping with landscape analysis of sociological, environmental and host/parasite genetic data. We explored the relationship between environmental features and gene flow of a filarial parasite of humans, Onchocerca volvulus, and its vector, blackflies in the genus Simulium. We generated a baseline microfilarial prevalence map from point estimates from 47 locations in the ecological transition separating the savannah and forest in Ghana, where transmission of O. volvulus persists despite onchocerciasis control efforts. We generated movement suitability maps based on environmental correlates with mitochondrial population structure of 164 parasites from 15 communities and 93 vectors from only four sampling sites, and compared these to the baseline prevalence map. Parasite genetic distance between sampling locations was significantly associated with elevation (r = .793, p = .005) and soil moisture (r = .507, p = .002), while vector genetic distance was associated with soil moisture (r = .788, p = .0417) and precipitation (r = .835, p = .0417). The correlation between baseline prevalence and parasite resistance surface maps was stronger than that between prevalence and vector resistance surface maps. The centre of the study area had high prevalence and suitability for parasite and vector gene flow, potentially contributing to persistent transmission and suggesting the importance of re-evaluating transmission zone boundaries. With suitably dense sampling, this framework can help delineate transmission zones for onchocerciasis and would be translatable to other vector-borne diseases.

Imitating the “breeder's eye”: Predicting grain yield from measurements of non‐yield traits

AbstractPlant breeding relies on information gathered from field trials to select promising new crop varieties for release to farmers and to develop genomic prediction models that can enhance the efficiency of genetic improvement in future breeding cycles. However, generating the genetic marker data required to apply genomic prediction at the early stages of a breeding program remains costly for many public‐sector breeding programs as well as for many plant breeders operating in developing countries. As the pace of climate change intensifies, the time lag of developing and deploying new crop varieties requires plant breeders to make selection decisions without knowing the future environments those crop varieties will encounter in farmers’ fields. Therefore, both lower cost and higher accuracy methods for prediction of crop performance are essential for creating and maintaining resilient agricultural systems in the latter half of the 21st century. To address this challenge, we conducted linked yield trials of 752 public maize (Zea mays) genotypes in two distinct environments. We developed and trained a phenotypic prediction model to predict yield from manually scored plant traits. The phenotypic prediction approach we employed outperformed genomic prediction in predicting yields in a second environment, with 8.7%–63% higher R2 and 4%–13% less root mean square error than the genomic prediction. The phenotypic prediction has the potential to be applied to a wider range of breeding programs, including those that lack the resources to genotype large populations, such as programs in the developing world, breeding programs for specialty crops, and public sector programs.

Causal influence of gut microbiota on small cell lung cancer: a Mendelian randomization study.

Previous studies have hinted at a significant link between lung cancer and the gut microbiome, yet their causal relationship remains to be elucidated. GWAS data for small cell lung cancer (SCLC) was extracted from the FinnGen consortium, comprising 179 cases and 218 613 controls. Genetic variation data for 211 gut microbiota were obtained as instrumental variables from MiBioGen. Mendelian randomization (MR) was employed to determine the causal relationship between the two, with inverse variance weighting (IVW) being the primary method for causal analysis. The MR results were validated through several sensitivity analyses. The study identified a protective effect against SCLC for the genus Eubacterium ruminantium group (OR = 0.413, 95% CI: 0.223-0.767, p = 0.00513), genus Barnesiella (OR = 0.208, 95% CI: 0.0640-0.678, p = 0.00919), family Lachnospiraceae (OR = 0.319, 95% CI: 0.107-0.948, p = 0.03979), and genus Butyricimonas (OR = 0.376, 95% CI: 0.144-0.984, p = 0.04634). Conversely, genus Intestinibacter (OR = 3.214, 95% CI: 1.303-7.926, p = 0.01125), genus Eubacterium oxidoreducens group (OR = 3.391, 95% CI: 1.215-9.467, p = 0.01973), genus Bilophila (OR = 3.547, 95% CI: 1.106-11.371, p = 0.03315), and order Bacillales (OR = 1.860, 95% CI: 1.034-3.347, p = 0.03842) were found to potentially promote the onset of SCLC. We identified potential causal relationships between certain gut microbiota and SCLC, offering new insights into microbiome-mediated mechanisms of SCLC pathogenesis, resistance, mutations, and more.

A survey on the perspectives of Irish pharmacists on the implementation of pharmacogenetics into pharmacy practice

Abstract Introduction Pharmacogenetics is the use of an individual’s genetic data to determine their response to a drug.[1] The incorporation of pharmacogenetic information into the prescribing process has the potential to improve patient outcomes by reducing adverse drug reactions and non-response to drugs.[1] Aim This study aims to evaluate the potential to implement pharmacogenetic testing and counselling into pharmacy practice in Ireland, by looking at the opinions of registered pharmacists on the potential new service. Methods A web-based survey, adapted from a previous survey,[2] was sent out to 6,236 pharmacists on the Pharmaceutical Society of Ireland’s mailing list using the software ‘Limesurvey’ in September 2019. Information was collected anonymously on demographics, knowledge, confidence, attitudes toward pharmacogenetic testing, and barriers and facilitators of pharmacogenetic testing. Quantitative analysis was undertaken using SPSS version 26, including descriptive analysis, correlations (Spearman’s Rho) and comparison of means (ANOVA). Knowledge scores were derived (number of correct questions out of 5), and converted to percentages. Responses to the open-ended question were analysed for recurring themes using qualitative content analysis. Results A response rate of 7.8% was attained with 486 analysable responses, 446 of which were full responses. Responses were submitted by 2.5 times more females than males and the majority came from pharmacists practising in community (56.4%) or hospital (25.3%). There was also a diversity of roles, ages and levels of experience represented. The mean knowledge score was 2.71 out of 5 (54.3%). However, the knowledge score of younger participants was significantly greater than those in the 61+ age bracket (p=0.007), with mean knowledge scores of 58% (20-30 years), 48% (41-50 years) and 40% (61+ years). A majority of respondents (60%) disagreed that their pharmacy education had prepared them sufficiently to counsel on pharmacogenetics. There was a significant relationship between a participant’s knowledge score and their self-reported confidence to discuss pharmacogenetics with other healthcare professionals (p&amp;lt;0.001). Many participants (&amp;gt;80%) agreed that pharmacogenetic testing had potential benefits for patient care. The open-ended question was answered by 17.4% of respondents. Barriers to introducing pharmacogenetic testing into pharmacy practice included ethical issues such as unauthorised access to private data and discrimination by insurance companies. A lack of resources including time and reimbursement were also noted as potential obstacles. Facilitators included an overall positive attitude towards the idea of pharmacogenetic testing. Conclusion Pharmacists already play an important role in medication management and health services. Given their knowledge and experience in the area, pharmacists are ideal candidates to introduce the idea of pharmacogenetic-guided prescribing into routine practice. From this study, it is apparent that for this implementation to occur, further education and training needs to be provided to pharmacists, as well as greater resources. While this study had the limitation of a low response rate, it was the first survey in Ireland to gather the perspectives of pharmacists on implementing pharmacogenetics in Ireland. As the survey was sent to all registered pharmacists, pharmacists from diverse settings and with varied years and types of experience answered this survey.

The role of dietary preferences in osteoarthritis: a Mendelian randomization study using genome-wide association analysis data from the UK Biobank.

To understand the impact of individual preferences for specific dietary items on OA, and to help inform the development of effective and targeted OA prevention and management strategies, we performed a Mendelian randomization analysis between dietary preferences and osteoarthritis. This study utilized genetic data from the UK Biobank to investigate the association between OA and 21 different common dietary items. Instrumental variables representing European populations were carefully selected based on their genetic significance and linkage disequilibrium. In cases where a dietary item had few relevant genetic markers, a more lenient selection threshold was applied. To prevent bias, the analysis excluded single nucleotide polymorphisms (SNPs) associated with factors such as body mass index (BMI) and cholesterol. Using inverse-variance weighting (IVW) and Mendelian randomization, significant associations were detected between certain dietary items and OA. Using Mendelian randomization to examine the relationship between 21 different dietary items and OA, significant associations were found for coffee, peas, watercress, and cheese, where the first two had a promoting effect and the last two an inhibiting effect on OA. Due to heterogeneity in the test results for cheese, a random IVW representation was used. The results of sensitivity analysis showed no significant heterogeneity or horizontal pleiotropy in the selected SNPS, demonstrating the reliability of Mendelian randomization analysis. This study identified coffee, peas, watercress, and cheese as food items that may have significant dietary effects on osteoarthritis. This information may be useful to consider in the development of OA management strategies.

Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Биологические механизмы тревожности: генетические ассоциации генов BDNF и AMPD1 с ситуативной и личностной тревожностью

&lt;p style="text-align: justify;"&gt;This article delves into the genetic underpinnings of anxiety, indicating that both state and trait anxiety have heritable components. However, there is no consensus on the degree of heritability, and much remains to be understood about the specific genetic variants involved and their mechanisms of action. The study explores the role of the &lt;em&gt;BDNF &lt;/em&gt;gene, which is involved in the synthesis and transportation of brain-derived neurotrophic factor protein, and the &lt;em&gt;AMPD1 &lt;/em&gt;gene, which facilitates the conversion of inosine monophosphate to adenosine monophosphate, the intracellular precursor for adenosine in the pathophysiology of anxiety. The methodology of this study involved a combination of genetic testing, psychological assessments, and statistical analysis. Participants were recruited from diverse demographic groups to ensure the findings were broadly applicable. DNA samples were collected for genetic testing, and participants completed the STAI questionnaire to measure their state and trait anxiety levels. The genetic data were analyzed to identify associations between variants in the &lt;em&gt;BDNF&lt;/em&gt; and &lt;em&gt;AMPD1&lt;/em&gt; genes and levels of anxiety; specifically, the frequency of these variants in participants with high anxiety scores was compared to those with low anxiety scores. The study provided evidence of the association between &lt;em&gt;BDNF &lt;/em&gt;variants and levels of trait anxiety and &lt;em&gt;AMPD1 &lt;/em&gt;variants with levels of state anxiety, implicating different biological mechanisms underlying these components of anxiety.&lt;/p&gt;

Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes

ObjectiveBreast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance.MethodsThis study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis.ResultsThe 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study’s bioinformatics analysis were validated through qRT-PCR experiments.Conclusion7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Genetic links between atopy, allergy, and alopecia areata: insights from a Mendelian randomization study

BackgroundAlopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and asthma.ObjectivesThis study aims to elucidate the genetic relationship between atopy, allergies, and alopecia areata (AA) using Mendelian randomization. We hypothesize that atopic and allergic conditions contribute to the genetic predisposition of AA.MethodsWe analyzed extensive genetic data from Genome-wide Association Studies (GWAS) involving over one million individuals. This analysis focused on assessing the genetic correlation between AA and various allergic conditions, including hay fever, eczema, asthma, and allergies to pollen, dust, and cats. The inverse variance weighted method served as our primary analytical tool, complemented by sensitivity analyses to verify the robustness of our results.ResultsOur findings reveal a significant genetic correlation between atopy/allergies and an increased risk of AA. Notably, strong associations were observed for hay fever, eczema, asthma, and specific allergies (pollen, dust, and cats). The sensitivity analyses corroborated these associations, reinforcing the reliability of our primary results.ConclusionsThis study provides compelling genetic evidence of an association between atopic and allergic conditions and the development of AA. These findings suggest that individuals with such conditions may benefit from enhanced surveillance for early signs of AA.

Complete Mitochondrial Genome of Four Peristediidae Fish Species: Genome Characterization and Phylogenetic Analysis

The systematic revision of the family Peristediidae remains an unresolved issue due to their diverse and unique morphology. Despite the popularity of using mitochondrial genome research to comprehensively understand phylogenetic relationships in fish, genetic data for peristediid fish need to be included. Therefore, this study aims to investigate the mitochondrial genomic characteristics and intra-family phylogenetic relationships of Peristediidae by utilizing mitochondrial genome analysis. Therefore, this study aims to investigate the phylogenetic relationship of Peristediidae by utilizing mitochondrial genome analysis. The mitochondrial genome of four species of Peristediidae (Peristedion liorhynchus, Satyrichthys welchi, Satyrichthys rieffeli, and Scalicus amiscus) collected in the East China Sea was studied. The mitochondrial gene sequence lengths of four fish species were 16,533 bp, 16,526 bp, 16,527 bp, and 16,526 bp, respectively. They had the same mitochondrial structure and were all composed of 37 genes and one control region. Most PCGs used ATG as the start codon, and a few used GTG as the start codon. An incomplete stop codon (TA/T) occurred. The AT-skew and GC-skew values of 13 PCGs from four species were negative, and the GC-skew amplitude was greater than that of AT-skew. All cases of D-arm were found in tRNA-Ser (GCT). The Ka/Ks ratio analysis indicated that 13 PCGs were suffering purifying selection. Based on 12 PCGs (excluding ND6) sequences, a phylogenetic tree was constructed using Bayesian inference (BI) and maximum likelihood (ML) methods, providing a further supplement to the scientific classification of Peristediidae fish. According to the results of divergence time, the four species of fish had apparent divergence in the Early Cenozoic, which indicates that the geological events at that time caused the climax of species divergence and evolution.