Genetic Link Research Articles

U-Pb dating of bastnäsite from the Vuoriyarvi massif: An example application for assessing the REE potential of carbonatite-related deposits

The Vuoriyarvi massif is a Devonian multistage alkaline-ultrabasic carbonatite complex within the Kola alkaline province. Dolomite carbonatites of the Vuoriyarvi massif contain abundant rare-earth mineralization mainly represented by ancylite-(Ce) and bastnäsite-(Ce). Ancylite was previously shown to have probably formed in the Devonian (ca. 365 Ma) during an early postmagmatic overprint. Previous geological observations have revealed a much later crystallization of bastnäsite but have not been able to specify the exact age of the mineralization. The in situ U-Pb dating of bastnäsite allowed us to constrain its genesis. Bastnäsite for this study was extracted from two varieties of dolomite carbonatite breccias cemented by (1) quartz-bastnäsite and (2) strontianite aggregates (hereafter bastnäsite-rich and strontianite-rich carbonatites – BRC and SRC, respectively). The obtained age estimations (237.7 ± 9.8 Ma and 239.9 ± 4.1 Ma, respectively) indicate that both studied rocks were formed during a single event. The revealed age difference (∼125 Ma) excludes the genetic link between the bastnäsite origin and regional alkaline magmatism, pointing out an additional source for the Vuoriyarvi bastnäsite-bearing rocks. Moreover, the obtained U-Pb ages provide strong evidence that a Triassic event is responsible for the occurrence of bastnäsite mineralization due to hydrothermal REE redistribution from the Devonian ancylite-rich carbonatites. Most of the REEs released during this process via dissolution of ancylite were precipitated in situ as bastnäsite, while strontium was transported and incorporated into strontianite. The Pb isotopic characteristics of bastnäsite (206Pb/204Pb = 18.1 ± 0.1, 207Pb/204Pb = 15.3 ± 0.1, and 207Pb/206Pb = 0.84 ± 0.01) are most probably inherited from the Devonian host rocks of the Vuoriyarvi massif involved in the Triassic overprint. Isotopic signatures of Pb, Sr, and Nd show that the depleted mantle and lower crust played the leading role in formation of the Vuoriyarvi alkaline complex. Taken together, the results of the present study negate the supergene origin of the Vuoriyarvi bastnäsite, implying that the bastnäsite mineralization is not confined to near-surface layers and, therefore, may be dispersed more broadly throughout the complex. These findings raise the question on underestimation of the probable REE reserves and lay the groundwork for a reassessment of the economic potential of the Vuoriyarvi complex.

Is Breathlessness Hampering Your Exercise? Watch Out, there can be a Genetic Link!

Is Breathlessness Hampering Your Exercise? Watch Out, there can be a Genetic Link!

Common and novel haplotype structures between different types of cancer.

Background: Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with cancer risk. GWAS data are important for cancer prevention and understanding the underlying mechanisms of cancer. This study aimed to investigate the genetic association between different types of cancer using GWAS data and a bioinformatics approach. The significant GWAS variants associated with more than one cancer type were identified. Common linkage disequilibrium (LD) variants between different types of cancer were identified by 1000 genomes phase 3 LD data. Haplotype blocks were identified by analyzing 1000 Genomes phase 3 genotyping data in the GWAS populations. Subsequent analyses included functional SNP analyses and TCGA gene expression. The results associated with significant GWAS variants (P<5E-8) showed the following haplotype associations in European population: GT rs4808075-rs8170 haplotype on BABAM1 with breast and ovarian cancers, GC rs16857609-rs11693806 haplotype on DIRC3 with breast and thyroid cancers, GCG rs380286-rs401681-rs31487 haplotype on CLPTM1L with skin and lung cancers, GGG rs4430796-rs11651052-rs11263763 haplotype on HNF1B with prostate and endometrial cancers, and GT rs10505477-rs6983267 haplotype on CASC8 associated with colorectal and prostate cancers. All these genes had significantly different expressions in tumor tissues (P<1E-3). In addition, the rs11693806 variant is located in the hsa-miR-873-5p binding site and has an enhancing effect on the hsa-miR-873-5p:DIRC3 interaction. These novel haplotype structures and miRNA:lncRNA interactions are important for understanding the common genetic link between cancers. These results can potentially be used in genetic panels.

Increased Positive Selection in Highly Recombining Genes Does not Necessarily Reflect an Evolutionary Advantage of Recombination.

It is commonly thought that the long-term advantage of meiotic recombination is to dissipate genetic linkage, allowing natural selection to act independently on different loci. It is thus theoretically expected that genes with higher recombination rates evolve under more effective selection. On the other hand, recombination is often associated with GC-biased gene conversion (gBGC), which theoretically interferes with selection by promoting the fixation of deleterious GC alleles. To test these predictions, several studies assessed whether selection was more effective in highly recombining genes (due to dissipation of genetic linkage) or less effective (due to gBGC), assuming a fixed distribution of fitness effects (DFE) for all genes. In this study, I directly derive the DFE from a gene's evolutionary history (shaped by mutation, selection, drift, and gBGC) under empirical fitness landscapes. I show that genes that have experienced high levels of gBGC are less fit and thus have more opportunities for beneficial mutations. Only a small decrease in the genome-wide intensity of gBGC leads to the fixation of these beneficial mutations, particularly in highly recombining genes. This results in increased positive selection in highly recombining genes that is not caused by more effective selection. Additionally, I show that the death of a recombination hotspot can lead to a higher dN/dS than its birth, but with substitution patterns biased towards AT, and only at selected positions. This shows that controlling for a substitution bias towards GC is therefore not sufficient to rule out the contribution of gBGC to signatures of accelerated evolution. Finally, although gBGC does not affect the fixation probability of GC-conservative mutations, I show that by altering the DFE, gBGC can also significantly affect nonsynonymous GC-conservative substitution patterns.

Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer-A Narrative Review (Endometriosis-Associated Cancer).

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.

Con7 is a key transcription regulator for conidiogenesis in the plant pathogenic fungus Fusarium graminearum.

The ascomycete fungus Fusarium graminearum is the primary cause of head blight disease in wheat and barley, as well as ear and stalk rot in maize. Given the importance of conidia and ascospores in the disease cycle of F. graminearum, precise spatiotemporal regulation of these biological processes is crucial. In this study, we characterized the Magnaporthe oryzae Con7p ortholog and discovered that FgCon7 significantly influences various crucial aspects of fungal development and pathogenicity. Notably, overexpression of FgABAA partially restored developmental defects in the FgCON7 deletion mutant. ChIP-qPCR analysis confirmed a direct genetic link between FgABAA and FgCON7. Furthermore, our research revealed a clear correlation between FgCon7 and chitin accumulation and the expression of chitin synthase genes. These findings offer valuable insights into the genetic mechanisms regulating conidiation and the significance of mycelial differentiation in this plant pathogenic fungus.

Re-evaluating the origins of sands in the Gurbantunggut Desert and its role as an aeolian dust contributor

We analyzed the trace and rare earth element contents of the desert sands and loess deposits in the Junggar Basin. Combined with previously published data, and using principal component analysis, our results provide insights into the sand provenances of the Gurbantunggut Desert in eastern Central Asia (CA); the genetic links between deserts and loess deposits in CA; and the specific sources in CA for the aeolian dust in North Pacific Ocean sediments. The results demonstrate the spatial heterogeneity of the geochemistry of sand across the Gurbantunggut Desert. The desert sands in the northern and western parts of this desert are mainly derived from the Altai and Junggar mountains, respectively, as supported by the directions of sand fluxes. However, Beitashan Mountain makes a negligible contribution due to the lack of fluvial transport and westward sand fluxes. However, more sediment samples need to be collected to confirm the contribution of Tianshan Mountains. Our findings also indicate that the Gurbantunggut Desert did not contribute significantly to loess accumulation on the northern slopes of the Tianshan Mountains, in accordance with the weak genetic relationships between loess deposits and deserts in western CA. We attribute this to the limited ability of the CA deserts to produce and supply dust-sized particles. Additionally, using the Metropolis-Hastings sampling approach, we find that the Gurbantunggut Desert is not the source region in CA for the fine dust particles in North Pacific Ocean sediments. Overall, our results contribute to a deeper understanding of the aeolian systems in CA and their impacts on the dust cycle at a hemispheric scale.

Fertility preservation before cancer treatment: the dilemma of saying 'no' as the price of glory.

A great deal of work has been carried out by professionals in reproductive medicine in order to raise awareness about fertility preservation (FP) techniques, particularly for women, and to ensure that FP is included in the care of young adults treated for cancer or a pathology requiring gonadotoxic treatment. If the importance of the development of our discipline is obvious, our militancy in favour of FP and our emotional projections must not make us forget that medical thinking must be carried out not only on a case-by-case basis, weighing up the benefit-risk balance, but also without losing sight that conceiving a child with one's own gametes is not a vital issue. The cultural importance given to the genetic link with offspring may bias patients' and physicians' decisions, while other ways of achieving parenthood exist, and are often more effective. Systematic information should be provided on the existence of FP techniques, but this should not lead to their systematic implementation, nor should it obscure that early information will also allow patients to begin projecting themselves in alternative options to become parents.

Genetic Evidence for Causal Relationships between Plasma Eicosanoid Levels and Cardiovascular Disease.

Cardiovascular diseases are the most common causes of mortality and disability worldwide. Eicosanoids are a group of bioactive metabolites that are mainly oxidized by arachidonic acid. Eicosanoids play a diverse role in cardiovascular diseases, with some exerting beneficial effects while others have detrimental consequences. However, a causal relationship between eicosanoid levels and cardiovascular disease remains unclear. Six single nucleotide polymorphisms (SNPs) with strong associations with plasma eicosanoid levels were selected. Summary-level data for cardiovascular disease were obtained from publicly available genome-wide association studies. A two-sample MR analysis identified that plasma eicosanoid levels were inversely correlated with unstable angina pectoris (OR 1.06; 95% CI 1-1.12; p = 0.04), myocardial infarction (OR 1.05; 95% CI 1.02-1.09; p = 0.005), ischemia stroke (OR 1.05; 95% CI 1-1.11; p = 0.047), transient ischemic attack (OR 1.03; 95% CI 1-1.07; p = 0.042), heart failure (OR 1.03; 95% CI 1.01-1.05; p = 0.011), and pulmonary embolism (OR 1.08; 95% CI 1.02-1.14; p = 1.69 × 10-6). In conclusion, our data strongly suggest a genetic causal link between high plasma eicosanoid levels and an increased cardiovascular disease risk. This study provides genetic evidence for treating cardiovascular diseases.

Integration of selective sweeps across the sheep genome: understanding the relationship between production and adaptation traits

BackgroundLivestock populations are under constant selective pressure for higher productivity levels for different selective purposes. This pressure results in the selection of animals with unique adaptive and production traits. The study of genomic regions associated with these unique characteristics has the potential to improve biological knowledge regarding the adaptive process and how it is connected to production levels and resilience, which is the ability of an animal to adapt to stress or an imbalance in homeostasis. Sheep is a species that has been subjected to several natural and artificial selective pressures during its history, resulting in a highly specialized species for production and adaptation to challenging environments. Here, the data from multiple studies that aim at mapping selective sweeps across the sheep genome associated with production and adaptation traits were integrated to identify confirmed selective sweeps (CSS).ResultsIn total, 37 studies were used to identify 518 CSS across the sheep genome, which were classified as production (147 prodCSS) and adaptation (219 adapCSS) CSS based on the frequency of each type of associated study. The genes within the CSS were associated with relevant biological processes for adaptation and production. For example, for adapCSS, the associated genes were related to the control of seasonality, circadian rhythm, and thermoregulation. On the other hand, genes associated with prodCSS were related to the control of feeding behaviour, reproduction, and cellular differentiation. In addition, genes harbouring both prodCSS and adapCSS showed an interesting association with lipid metabolism, suggesting a potential role of this process in the regulation of pleiotropic effects between these classes of traits.ConclusionsThe findings of this study contribute to a deeper understanding of the genetic link between productivity and adaptability in sheep breeds. This information may provide insights into the genetic mechanisms that underlie undesirable genetic correlations between these two groups of traits and pave the way for a better understanding of resilience as a positive ability to respond to environmental stressors, where the negative effects on production level are minimized.

Genetic association between gut microbiome and blood pressure and blood cell count as mediator: A two-step Mendelian randomization analysis

BackgroundPrevious studies have established a genetic link between gut microbiota and hypertension, but whether blood cell count plays a mediating role in this remains unknown. This study aims to explore genetic associations and causal factors involving the gut microbiome, peripheral blood cell count, and blood pressure. MethodsWe utilized summary statistics derived from genome-wide association studies to conduct a two-sample mediation Mendelian randomization analysis (https://gwas.mrcieu.ac.uk/). We applied inverse variance weighted (IVW) estimation method as the primary method, along with MR Egger, Weighted median, Simple mode and Weighted mode as complementary methods. To ensure the robustness of the results, several sensitivity analyses were conducted. ResultsGenetic variants significantly associated with the microbiome, blood pressure, or peripheral blood cell counts were selected as instrumental variables. Fourteen microbial taxa were found to have suggestive associations with diastolic blood pressure (DBP), while fifteen microbial taxa showed suggestive associations with systolic blood pressure (SBP). Meanwhile, red blood cell count, lymphocyte count, and platelet count were identified to mediate the influence of the gut microbiome on blood pressure. Specifically, red cell count was identified to mediate the effects of the phylum Cyanobacteria on DBP (mediated proportion: 8.262 %). Lymphocyte count was found mediate the effects of the genus Subdoligranulum (mediated proportion: 2.642 %) and genus Collinsella (mediated proportion: 2.749 %) on SBP. Additionally, platelet count was found to mediate the relationship between the genus Eubacterium ventriosum group and SBP, explaining 3.421 % of the mediated proportion. ConclusionsOur findings highlighted that gut microbiota may have causal influence on the blood pressure by modulating blood cell counts, which sheds new light on the pathogenesis and potential clinical interventions through the intricate axis of gut microbiome, blood cell counts, and blood pressure.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low BMD (typically < -2.5 SD), causes a higher fracture risk and leads to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians (EAS). We investigated the genetic aspects of BMD in 86 716 individuals from the Taiwan Biobank and their causal links to health conditions within EAS. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-β. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with BMI and type 2 diabetes (T2D) in EAS. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, hemoglobinA1c, and reduced T2D risk. Bidirectional Mendelian randomization analyses revealed that a higher BMI causally increases BMD in EAS. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in EAS, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

Deciphering the Genetic Links between Psychological Stress, Autophagy, and Dermatological Health: Insights from Bioinformatics, Single-Cell Analysis, and Machine Learning in Psoriasis and Anxiety Disorders.

The relationship between psychological stress, altered skin immunity, and autophagy-related genes (ATGs) is currently unclear. Psoriasis is a chronic skin inflammation of unclear etiology that is characterized by persistence and recurrence. Immune dysregulation and emotional disturbances are recognized as significant risk factors. Emerging clinical evidence suggests a possible connection between anxiety disorders, heightened immune system activation, and altered skin immunity, offering a fresh perspective on the initiation of psoriasis. The aim of this study was to explore the potential shared biological mechanisms underlying the comorbidity of psoriasis and anxiety disorders. Psoriasis and anxiety disorders data were obtained from the GEO database. A list of 3254 ATGs was obtained from the public database. Differentially expressed genes (DEGs) were obtained by taking the intersection of DEGs between psoriasis and anxiety disorder samples and the list of ATGs. Five machine learning algorithms used screening hub genes. The ROC curve was performed to evaluate diagnostic performance. Then, GSEA, immune infiltration analysis, and network analysis were carried out. The Seurat and Monocle algorithms were used to depict T-cell evolution. Cellchat was used to infer the signaling pathway between keratinocytes and immune cells. Four key hub genes were identified as diagnostic genes related to psoriasis autophagy. Enrichment analysis showed that these genes are indeed related to T cells, autophagy, and immune regulation, and have good diagnostic efficacy validated. Using single-cell RNA sequencing analysis, we expanded our understanding of key cellular participants, including inflammatory keratinocytes and their interactions with immune cells. We found that the CASP7 gene is involved in the T-cell development process, and correlated with γδ T cells, warranting further investigation. We found that anxiety disorders are related to increased autophagy regulation, immune dysregulation, and inflammatory response, and are reflected in the onset and exacerbation of skin inflammation. The hub gene is involved in the process of immune signaling and immune regulation. The CASP7 gene, which is related with the development and differentiation of T cells, deserves further study. Potential biomarkers between psoriasis and anxiety disorders were identified, which are expected to aid in the prediction of disease diagnosis and the development of personalized treatments.

Characterization of rice (Oryza sativa L.) landraces from Majuli and surrounding riverine ecologies in Assam: Assessment of morphogenetic variability and submergence tolerance

AbstractRice landraces from the fragile riverine ecosystems surrounding Majuli islands in Assam are pivotal for local livelihoods, as well as for their potential in developing flood tolerant varieties. We characterized 87 landraces from Majuli, Dhemaji, and North Lakhimpur districts in Assam by assessing 36 agro‐morphological traits, submergence tolerance, and microsatellite diversity. Multivariate analyses revealed that grain and leaf characteristics, plant height, and tillering are important traits differentiating the cultivar types. Sixty‐six SSR markers generated 271 alleles with an average of 4.1 alleles per marker with population structuring in two clusters having an allele frequency divergence of 0.124. The Bao or deep‐water landraces displayed the highest phenotypic and genetic diversity, with potential genetic links to the aus and wild species. Sali (winter rice) and bora (sticky rice) landraces were predominantly indica type. Nearly 47% of the germplasm exhibited tolerance to two‐week submergence at seedling stage. Surveying SUB1A and SNORKEL genes revealed the presence of SUB1A‐1 and SNORKEL genes in 64% and 57% of the tolerant accessions, respectively. This study highlights the untapped potential of rice landraces in a fragile ecological region, providing insights into their agronomical traits, submergence tolerance, and genetic diversity. The findings lay the foundation for improved germplasm management and developing flood‐resilient rice varieties, crucial for sustainable agriculture in riverine ecosystems.

Ultrahigh-temperature crustal anatexis and final cratonization in Eastern Hebei, North China Craton: Insights from ca. 2.46 Ga Taipingzhai enderbites

Charnockitic rocks are a suite of granulite-facies plutonic rocks that include dominantly granitic−tonalitic and partly dioritic rocks. The Na-rich endmembers of the charnockite series, including dioritic to tonalitic rocks, are also termed enderbites. Charnockitic rocks are the main component of the cratonic-type lower continental crust in Precambrian cratons worldwide. These rocks are generally considered to be products of the anatexis of the lower crust under high- to ultrahigh-temperature conditions and play a key role in stratification between upper and lower crustal layers as well as the cratonic stabilization (cratonization) of Precambrian continents, although further study is required to gather detailed information about these rocks. In this study, a group of igneous enderbites (dioritic−tonalitic charnockites) from Eastern Hebei, North China Craton, is investigated. Zircon U-Pb dating reveals that the enderbites formed at ca. 2.46 Ga, which is coeval with the regional granulite-facies metamorphic overprinting. The enderbites are primarily composed of clinopyroxene, orthopyroxene, plagioclase, and quartz, with minor amphibole, biotite, K-feldspar, and Fe-Ti oxides. The rocks are characterized by high Fe2O3T + MgO (9.80−15.9 wt%), Cr (71.0−292 ppm), and Ni (41.2−107 ppm) contents, as well as low Al2O3 (13.9−16.6 wt%) and K2O (1.07−2.43 wt%) contents, with high Na2O/K2O ratios (1.51−4.43) and low Sr/Y (24.5−49.5) ratios. Moreover, these rocks are enriched in light rare earth elements (LREEs), (La/Yb)N = 8.06−17.8, and yield weak Eu anomalies, (Eu/Eu* = 0.80−1.18), with negative Th, U, Ta, Nb, and Ti anomalies. Various mineral thermobarometers, oxybarometers, and hydrometers are used to constrain the crystallized P-T-ƒO2-H2O conditions of the enderbites. These rocks crystallized at high temperature (860−1000 °C), crystallization pressure (8.0 ± 1.0 kbar), and H2O-poor (1.5−2.4 wt%) conditions, with oxygen fugacities (ΔQFM) of 0.0−3.0, which suggests “hot” (high-temperature) and “dry” (water-poor) crystallization conditions. The enderbites also have heterogeneous in situ zircon Hf-O isotopic compositions: εHf(t) = 2.4−7.5; δ18O = 5.78‰−7.74‰. These new data, combined with trace element characteristics, suggest that the enderbites were derived from the partial melting of metabasites, and that assimilation and fractional crystallization controlled the compositional variation in the enderbites. Further thermodynamic and geochemical modeling suggests that the anatexis of Mg-Fe−rich metabasite under ultrahigh-temperature (&amp;gt;1000 °C) and H2O-poor (1.0−1.5 wt%) conditions at a low crustal depth (∼9.0 kbar) could yield a melt composition comparable to that of the observed enderbites. Postcollisional lithospheric extension and mafic magma underplating prompted the partial melting of lower crustal metabasite at ultrahigh temperatures and normal lower crustal depths, resulting in the formation of enderbites. This study demonstrates that the enderbites could be formed by ultrahigh-temperature anatexis of metabasite with amphibole dehydration melting (Pl + Amp → Opx + Cpx + melt) and offers robust evidence of the genetic links between the ultrahigh-temperature anatexis of basic rocks and the generation of enderbites. In addition, the occurrence of ca. 2.46 Ga enderbites may mark the final cratonization of the North China Craton, and the ca. 2.50−2.45 Ga tectono-thermal event was an ultrahigh-temperature metamorphic-anatexis process rather than simple regional granulite metamorphic overprinting. Therefore, the generation and emplacement of enderbites involved not only a magmatic process but also an element redistribution process in the lower crust, which has important implications for stabilization of the North China Craton at ca. 2.5 Ga.

Exploring the interconnected between type 2 diabetes mellitus and nonalcoholic fatty liver disease: Genetic correlation and Mendelian randomization analysis.

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.

Petrogenesis of the Bastielieke W-mineralized granitic pluton in the Altai orogen, NW China

Granitic magmatism of the Altai orogen is the key to understanding the tectonic evolution and metallogeny in the Central Asian Orogenic Belt (COAB). In this paper, we conducted comprehensive petrological, geochronological and geochemical investigations on the Bastielieke granitic pluton in the Altai orogen. Zircon U–Pb dating shows an emplacement age of 278–270 Ma for the pluton. Granites of the Bastielieke pluton have S-type granitic affinity and have Zr + Nb + Ce + Y contents (76.6–272 ppm), A/CNK ratios > 1.1, and K2O > Na2O. The low εNd(t) (−2.8 to + 2.9) and high εHf(t) (+7.6 to + 15.9) values with Nd-Hf isotope decoupling, invariable Pb isotopes, and moderate zircon δ18OV-SMOW values suggest crustal recycling of sedimentary rocks in a syn- to post-collision setting. In addition, the pluton is spatially related to the tungsten (W) deposit and also temporally consistent with the mineralization age of 284 ± 6 Ma, indicating a genetic link between the Early Permian magmatism and mineralization in Bastielieke. Furthermore, the source rocks of the pluton which are sedimentary rocks and abundant in W, provide the material basis for the initial enrichment of W in primary magmas. Given high Rb/Sr (>3) and low K/Rb ratios (<200), we interpret that the pluton has experienced high differentiation. Our studies propose that the termination of the subduction-accretion of the Paleo-Asian Ocean and the initiation of a syn- to post-collision regime for the Altai orogen are probably at the Early Permian.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Potential risk factors for hypospadias and negative correlation with DICER1 (rs3742330) A>G variant in Algerian population: A case-control study.

Hypospadias continues to be a prevalent congenital anomaly affecting the male external genitalia, characterized by an unclear origin and complex treatment approaches. This study aimed to investigate the risk factors associated with hypospadias and explore its genetic link with the DICER1 rs3742330 variant. The study involved two groups: 105 male children with hypospadias and 111 healthy male children as matched controls. Detailed history and physical examinations were conducted for all patients and controls. PCR-restriction fragment length polymorphism was utilized to identify the DICER1 rs3742330 variant, analyzing genotype distribution and allele frequency. Logistic regression analysis estimated the risk factors for hypospadias. The mean age in the hypospadias group was 4.56 ± 2.50 years. The most prevalent type of hypospadias observed was the anterior type in 60 children (57.14%). Intrauterine growth restriction, advanced maternal age, and gestational hypertension were identified as significant risk factors for hypospadias (p = .011, p = .016, and p = .041, respectively). Regarding the genetic study, no significant difference was found in both genotype and allele frequencies of the DICER1 rs3742330 variant between case and control groups. The rs3742330 variant in the DICER1 gene showed no association with hypospadias cases in the Algerian population. However, multivariate logistic regression analysis identified preterm birth, low birth weight, intrauterine growth restriction, advanced maternal age, gestational diabetes, and rural residence as the most significant independent predictors for hypospadias.

Syntectonic Shear-induced Emplacement of Crystallizing Granite Magmas Evident from Magmatic Shear Sense, Mafic Schlierens, and Microgranular Enclaves in the Mesoproterozoic A-type Kanigiri Pluton, Nellore Schist Belt, Southeast India

ABSTRACT The observations on field-based mesoscale magmatic structures suggest that the A-type Kanigiri granite (KG) pluton, Nellore Schist Belt (NSB) has undergone a long plutonic history as evidenced by the continuum of deformation from early magmatic to the ductile regime at the waning stage of pluton evolution. The linear alignment of the KG pluton, which lies sub-parallel to the regional Terrane Boundary Shear Zone (TBSZ), and the long-standing deformation regime indicate the genetic link with this shear zone. The formation of mafic schlierens in the KG pluton owes to the mechanical crystal flow-sorting process during the replenishment of KG magma, which is further induced by the injection of crystal-charged microgranular enclave (ME) magmas in the crystallizing felsic magma chamber. The outflown ME magma blobs from the walls of the conduit during the invasion trigger the local turbulence, resulting the swirling of early crystallized mafic crystals of the host KG magma. This kind of swirling in the host KG magma must have been formed at an early stage of crystallization i.e., crystal-poor condition of the KG melts. When the MEs flow out, gravity causes them to interact with the host KG magma and attempt to dissolve into it. This results in schlieren rims formed around the MEs. The magmatic shearing observed in the KG pluton results from an active crystal-mush environment due to accumulated strain caused by the syntectonic movement as evidenced by the magmatic sense of shears. The locally formed slickensides are sub-magmatic origin during the upward pushing of replenishing ME and another pulse of KG magma. The presence, spread and prevalence of magmatic structures like ME magma globules, magma flowage, mafic schlierens, slickensides and shear sense indicators in the KG pluton suggest that the KG pluton underwent dynamic magma emplacement and evolution due to a shear zone, probably the TBSZ, which acted upon KG pluton in a syntectonic environment.