The Wadi Ranga-Atshan metavolcanic (WRAM) suite in the Southern Eastern Desert of Egypt is part of the Shadli calc-alkaline metavolcanic belt, which is the main crustal part of the Arabian-Nubian Shield (ANS). Integrated remote sensing, mineral compositions, and whole-rock chemical data are used to elucidate the mantle-plume contribution, petrogenesis, and geodynamic evolution of the ~ 739 Ma Shadli metavolcanics. Remote sensing analysis using Landsat-8 and ASTER band ratios in RGB effectively discriminates between the dominant felsic and mafic varieties (bimodal volcanism) and minor intermediate types along with the different alteration zones (e.g., iron- and Al‒OH-rich zones). Its PCA and CEM techniques are used to delineate phyllic, argillic, and propylitic alteration zones and their associated Cu-Fe-Zn sulfides, iron oxides, and malachite mainly along the NW-SE shear zones. The whole rock chemistry indicates that mafic rocks (metabasalts) and felsic to intermediate types (metarhyolites, metadacites, and metabasaltic andesites) show tholeiitic and calc-alkaline natures, respectively. But alkali metabasalts exhibit alkaline affinity. The calc-alkaline metavolcanic protoliths are derived from 10-20% partial melting of a depleted spinel lherzolite mantle source, supported by their low REEs (ΣREEs < 20 ppm) contents. They are further characterized by enrichment in LILEs and depletion in HFSEs (Nb < 2.6, Ta < 0.08, and Ti < 53.31 ppm), suggesting a typical arc-related magmatic signature. In contrast, the alkali metabasalt protoliths are derived from low partial melting (~ 5% melting) of the enriched garnet lherzolite or garnet-spinel lherzolite source in deeper and enriched mantle parts, supported by their high REEs (ΣREEs: 212 ppm) contents. The alkali metabasalts are strongly enriched in HFSEs (Ti > 14,676, Nb > 28.9, and Ta > 1.7 ppm) along with high Cr (up to 337.8 ppm) and Ni (up to 245.1 ppm) relative to calc-alkaline types, consistent with intraplate (OIB-like type) magmatism due to upwelling of mantle plume. The investigated metavolcanics plot in MORB-arc and within-plate/OIB fields, reflecting coexistence of OIB-like (mantle plume-derived melts) and arc/MORB-like basaltic melts, together with arc-like magma signatures; these results indicate tectonomagmatic evolution of the studied rocks from supra-subduction arc magmatism to intraplate rifting transition during the arc assembly of the ANS. Therefore, the different partial melting, magmatic affinity, and magma source (mixed plume-arc magmas) possibly reflect plume-driven magmatism during the subduction-rift transition of the ANS. This transitional environment may be characterized by a sequence of magmatic sulfide mineralization (disseminated pyrite and chalcopyrite) to post-magmatic hydrothermal alteration and supergene oxidation assemblages (gossans, talc-carbonate, malachite, and chrysocolla). These processes were structurally controlled by NW-SE (Najd-related) and NE-SW shear zones that developed during the subduction-rift transition, which facilitated mantle-derived magmatism and fluid migration, thereby generating volcanogenic massive sulfide (VMS) mineralization. The arc-related hydrothermal systems, plume-related ore systems, and later metasomatic overprints may highlight the metallogenic significance of the ANS.
Metasomatized lithospheric mantle plays a critical role in the petrogenesis of CO2-rich magmas, which are important hosts of rare-earth element deposits. However, the relationship between the structure of the lithosphere and the global distribution of CO2-rich magmas remains poorly quantified. Here we analyse the locations of young (<200 million years ago) continental intraplate CO2-rich silicate magmas and magmatic carbonatites in conjunction with upper-mantle shear-wave velocity anomalies and lithospheric thickness estimates. Our results document systematic increases in lithospheric thickness with estimated magma CO2 content from basanites (<5 wt% CO2), which erupt through seismically slow and thin non-cratonic lithosphere, to nephelinites, melilitites and ultramafic lamprophyres, which occur within progressively faster, thicker lithosphere and, finally, to lamproites and kimberlites (<20 wt% CO2), which are emplaced on thick cratonic lithosphere. Carbonatites are associated with lithospheric thicknesses similar to those of nephelinites, melilitites and ultramafic lamprophyres, implying the derivation of carbonatites from these mafic CO2-rich silicate magmas via liquid immiscibility and/or fractional crystallization. We illustrate our lithospheric thickness-magma type relationship using Cretaceous-Pleistocene alkaline magmatism across western North America, ultimately demonstrating how lithospheric thickness controls the global occurrence of CO2-rich magmas and, consequently, their associated rare-earth element deposits.
Magma convection is a mechanism that greatly enhances heat transfer from mobilizable, crystal-poor magma bodies to the surrounding immobile, crystal-rich mush reservoir of Earth's igneous systems. As most of these systems are geophysically shown to be mush-dominated, magma convection is often omitted from thermo-kinetic models, and its role in magma evolution and eruptibility remains underexplored. Here we present 2-D numerical thermal modelling that parameterizes magma convection through a Nusselt-number approach that describes the local enhancement of heat transfers, and examine its effects in the axial mush zone of fast-spreading mid-ocean ridges. We demonstrate that magma convection, while not affecting the overall thermal regime of the mushy reservoir, significantly reduces the lifespan of individual pockets of eruptible melt to <2 years, which is two orders of magnitude shorter than in simulations without convection. Our models also show that magma convection could promote mush reheating and unlocking, potentially participating to the geochemical homogenization of heterogeneous melts extracted from the mantle. Predicted fluctuations in the occurrence and persistence of magma bodies provide insights into their highly transient nature, enhancing our ability to interpret geophysical snapshots of magma-mush systems in oceanic settings, and in other igneous systems.
Large dikes are the main mechanism of crustal extension in volcanic areas, but the processes in the underlying magma system that supply the required volumes remain unclear. We show that 1.4 cubic kilometers of magma propagated under the Ethiopian rift in December 2024 and continued for ~3 months. Geodesy and seismicity reveal that the dike was fed from a network of magma reservoirs between 6 to 12 kilometers in depth with pathways rapidly forming between them. We calculate pressure changes in the reservoirs and show that underpressure developed in the deeper portion, creating the conditions to drain large magma volumes. We find that tectonic stress and availability of magma alone are not enough to drive intrusion of massive dikes. These events will start only after magma connectivity and deep underpressure develop. Similar conditions may be important for the transfer of large magma volumes from the mantle and the formation of large igneous provinces.
The impact of rainfall-driven erosion on the evolution of magmatic systems and, ultimately, on volcanic activity, is an emerging topic of critical importance in the context of the ongoing climate crisis. While tectonic forces control magma intrusion through the crust, climatic factors (i.e., rainfall) may influence magma ascent and contribute to volcanic eruptions. Here, we present a set of innovative analogue models integrating uplift driven by magma intrusion, and surface processes triggered by a rainfall system. By varying magma injection rates and rainfall intensities, we examine surface morphology under different conditions. Our models reveal that the topographic elevation, a proxy for the effectiveness of surface processes, does not correlate with increasing rainfall intensity. Only under heavy rainfall rates, the system significantly erodes and relocates material from the top of the rising dome to its rim, likely modulating magma ascent. Under this condition, the resulting topographic dome shows the lowest elevation and the greatest accommodation volume. We then speculate that the erosional unloading of the overburden could increase the magmatic chamber's force to cause uplift. Ultimately, although the present work represents an initial study, we emphasize how extreme rainfall events might drive magmatic systems toward a more critical state.
Crystallisation kinetics play a fundamental role in controlling conduit dynamics and eruptive style. The degree of superheating is critical in controlling crystallisation kinetics; however, its effect is still debated and has an unclear impact on eruption dynamics. Here, we investigate how superheating influences clinopyroxene nucleation in tephritic magmas from the 2021 Tajogaite eruption (La Palma, Spain) through both in situ and ex situ view experiments. Our findings show that superheating delays nucleation by dissolving pre-existing nuclei, thereby inhibiting crystallisation upon return to subliquidus conditions. Using a numerical model, we investigate how different nucleation delays resulting from different degrees of superheating affect magma ascent dynamics. Depending on the initial thermodynamic conditions and on the pre-eruptive history of magma, an increased nucleation delay can significantly reduce crystal content during ascent, lowering magma viscosity and affecting eruptive style. These findings highlight the critical role of pre-eruptive thermal histories in controlling eruptive style, and provide constraints for refining experimental protocols and numerical models, with direct implications for improving volcanic hazard assessment and eruption forecasting.
The geological origins of iron oxide-apatite (IOA) rocks, important resources for iron and rare-earth elements, are intensely debated. Using triple oxygen isotope data, we here show that magnetite from IOA deposits near Kiruna, northern Sweden, and related igneous rocks contain high concentrations of oxygen derived from evaporitic sulfate. To explain these observations, we propose that the Kiruna IOA assemblage formed in response to massive assimilation of evaporites by silicate magmas. sulfate from the evaporites would have oxidised ferrous iron in these magmas, facilitating the formation of immiscible ferric iron-rich melts and/or magnetite, which then separated from the magmas to form ore deposits. Ferric iron-bearing fluids with low Δ'17O values, exsolved from the silicate magmas or the ore-forming melts, would have crystallised additional magnetite. An inventory study reveals that Proterozoic and Cambrian IOA deposits have lower Δ'17O values than post-Cambrian IOA deposits. This shows that the Δ'17O values of global IOA deposits reflect the changing isotope composition of atmospheric O2 incorporated by evaporitic sulfate over time, and demonstrates that oxygen released from evaporitic sulfate is a common component in IOA deposits.
Rare earth elements (REE) are essential for low-carbon and digital technologies, yet their primary sources remain geologically restricted and geopolitically vulnerable. This study shows that volcanic geothermal skarn systems can host substantial high REE concentration. Using core and cutting samples from a 2500 m deep geothermal borehole in the Sabatini volcanic district (central Italy), we reconstruct the chemical zonation and metasomatic evolution of calc-silicate reservoir formed by high-temperature fluid-mediated magma-carbonate interaction. Whole-rock and mineral chemistry indicate that light REE (LREE) are concentrated in an upper (ca. 400 m thick) vesuvianite-rich interval, whereas heavy REE (HREE) are preferentially incorporated in garnet at greater depths. Vesuvianite is identified as the dominant REE host (> 9000 ppm total REE), and accounting for most of the REE budget. Although the economic potential of the Sabatini skarn reservoir remains to be evaluated, geometry-based estimates indicate the Sabatini skarn as a potentially high-grade REE deposit at global scale. The widespread occurrence of similar skarn systems in Quaternary volcanic districts of Italy, coupled with extensive carbonate decarbonation in magmatic arcs, suggests that fluid-mediated magma-carbonate interaction in volcanic environments may represent an unexplored mechanism for REE enrichment and redistribution of metals within the continental crust.
Hydrothermal sulfide deposits (e.g., porphyry and skarn) associated with felsic magmatism are major sources of chalcophile metals, including copper (Cu), molybdenum (Mo), gold (Au), lead (Pb), zinc (Zn), silver (Ag), and tin (Sn). However, the source of sulfur and metals remains debated. We report a study of clinopyroxene-hosted sulfide inclusions in mafic enclaves from the Beidashan granitic pluton (Northeast China), associated with a giant Sn-Pb-Zn-Ag-Cu deposit. Evidence shows the following: (i) immiscibility among Cu- and Zn-rich sulfide liquid, a silicate liquid, and an aqueous fluid during mafic magma emplacement in the upper crust; (ii) metal enrichment in FeS [iron(II) sulfide]-dominated melt inclusions (∼2628 parts per million of Cu, ∼233 parts per million of Zn, ∼275 parts per million of Pb, and ∼2.0 parts per million of Sn), reflecting strong partitioning into sulfide melts; and (iii) oxidative dissolution of sulfides by exsolved fluids, enabling metal transfer to the overlying felsic magma. The study demonstrates that metals in felsic-hosted deposits are sourced from subjacent mafic magmas and that mafic-felsic interaction triggered sulfide liquid/aqueous fluid cosaturation, ensuring efficient fluid-mediated chalcophile metal dissolution and transfer.
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), shows marked clinical heterogeneity despite a shared immune-genetic background. The adult spatial contexts through which inherited IBD susceptibility is expressed remain unclear. We integrated GWAS summary statistics for overall IBD, CD, and UC with LDSC, stratified LDSC, LDSC-SEG, MAGMA, PoPS, and genetically informed spatial mapping (gsMap). Human genetic signals were projected onto the E16.5 mouse single-cell spatial atlas as an exploratory developmental reference, and adult disease-tissue spatial support was assessed across SCP2959 CD spatial sections and GSE189184 idiopathic UC inflamed Visium sections. PoPS-independent MAGMA-only module-score and FUSION-TWAS sensitivity analyses, together with targeted RT-qPCR in NCM460 epithelial cells and THP-1-derived macrophage-like cells were performed. LDSC showed strong positive genetic correlations among overall IBD, CD, and UC, including overall IBD versus CD (rg = 0.9458, P = 1.79 × 10-8), overall IBD versus UC (estimated rg = 1.0907, P = 3.48 × 10-6), and CD versus UC (rg = 0.9535, P = 0.0133). MAGMA and PoPS prioritized immune-inflammatory candidates, including IL23R, JAK2, STAT3, CCL2, NOD2, and HLA-region genes. Exploratory developmental gsMap showed nominal signals in gastrointestinal, liver, smooth-muscle, epidermal, and neural regions. In adult disease-tissue gsMap, overall IBD signals showed FDR-significant enrichment in SCP2959 CD immune regions (ACAT P = 3.52 × 10-7, q = 1.41 × 10-6), lamina propria (ACAT P = 2.75 × 10-5, q = 4.27 × 10-5), follicular clusters (ACAT P = 7.31 × 10-7, q = 1.10 × 10-5), and myeloid clusters (ACAT P = 6.67 × 10-6, q = 3.34 × 10-5). In GSE189184 idiopathic UC inflamed tissue, enrichment was observed in GWAS-independent immune-rich (ACAT P = 1.72 × 10-5, q = 1.38 × 10-4), structural/barrier (ACAT P = 7.52 × 10-5, q = 3.01 × 10-4), epithelial-mucosal (ACAT P = 9.08 × 10-4, q = 0.00182), inflammation-repair (ACAT P = 0.00140, q = 0.00224), and stromal-fibrotic domains (ACAT P = 0.00268, q = 0.00357). MAGMA-only module-score and FUSION-TWAS sensitivity analyses provided PoPS-independent support for the adult lesion-context interpretation. RT-qPCR showed that JAK2 knockdown reduced cytokine-induced CCL2 and CXCL8 by 52.6% and 36.9% and partially restored OCLN expression, while LPS induced IL1B, TNF, CCL2, and PYCARD in macrophage-like cells. Shared IBD genetic liability was most consistently linked to an adult immune-epithelial inflammatory lesion program involving immune-rich, epithelial-inflammatory, myeloid/follicular, lamina propria, structural/barrier, and remodeling-associated contexts. Developmental and subtype-weighted spatial signals, including neural-related signals in the embryonic reference, should be viewed as hypothesis-generating clues to developmental and neuroimmune programs rather than definitive subtype-specific mechanisms.
The recent discovery of a 4.1-billion-year-old (Ga) Martian gabbroic diorite enables an assessment of water reservoirs on early Mars. Measurements of H2O and D/H in igneous Ca-phosphates record mixing between D-poor magmatic water and a D-rich component that retains an imprint of the ancient Martian hydrosphere. The D/H ratio of magmatic water is similar in Martian magmas with different ages and mantle sources, indicating that early differentiation processes did not fractionate H isotopes in the primordial Martian mantle. The D-rich component was assimilated by migrating magmas that interacted with aqueously altered basaltic crust. Our minimum bound on the D/H ratio of the Martian hydrosphere at 4.1 Ga (~2× the D/H ratio of Earth seawater) supports models of rapid H loss to space from Mars' juvenile atmosphere.
Supported by the mush model, the origin of crystal-poor, high-silica rhyolitic magmas (≥ 75 SiO₂ wt.%) is commonly linked to melt extraction in shallow, crystalline mushes, yet their complementary cumulates remain elusive in the upper crust. Here we present the "dynamic mush model" for the Campo Alegre-Corupá system (Brazil), combining textural analysis and thermodynamic modeling to show that high-silica melts formed through upper-crustal fractionation, leaving a granitic residue and feeding a caldera-forming eruption. Syenites and melasyenites represent their silicic-mafic cumulates, the syenites being formed at relatively low crystallinities (~16-33 of bulk vol.%) after extraction of large amounts of interstitial melts (~47-80 of liquid vol.%). In contrast to static models (extraction window ~50-70 vol.%), our results indicate early melt segregation in a dynamic reservoir. Alkali-feldspar crystals were size-selectively and hydraulically sorted by upward melt flow; aggregates were then formed at low crystallinities, supposedly via synneusis, enabling rapid sinking, and were repacked by recharge. This process, enhanced by relatively high magma fluxes, efficiently separated crystals from melt, explaining the origin of large-volume eruptible magmas in the upper crust. Our findings redefine mush evolution while underscoring the role of flow-driven crystal sorting (elutriation) in caldera-forming systems.
Observational studies link opioid use to lung cancer risk, but findings are inconsistent due to potential confounding and reverse causality. Whether these associations reflect shared genetic liability with histologic lung cancer (LC) subtypes is unknown. This study quantified genome-wide genetic overlap and modeled their latent shared architecture. This analysis used European-ancestry genome-wide association study (GWAS) summary statistics for opioid use traits (codeine/tramadol and dihydrocodeine) and lung cancer outcomes (overall lung cancer, non-small cell lung cancer, adenocarcinoma, and squamous cell carcinoma). Bivariate linkage disequilibrium score regression (LDSC) estimated heritability and genetic correlations. Genomic structural equation modeling (Genomic SEM) tested latent factor models, and multi-marker analysis of genomic annotation (MAGMA) performed gene, pathway, and tissue enrichment analyses. An exploratory Mendelian randomization (MR) analysis was additionally conducted when adequate instrumental variants were available. LDSC indicated uniformly positive genetic correlations between opioid traits and lung cancer outcomes, strongest for CT-NSCLC (rg = 1.1017, p = 6.86 × 10- 4) and DHC-NSCLC (rg = 0.9773, p = 4.46 × 10- 2); other positive pairs included DHC-LC (rg = 0.5938, p = 1.59 × 10- 5) and DHC-SCC-L (rg = 0.6366, p = 9.03 × 10- 4), with remaining correlations smaller but positive (CT-LC rg = 0.2702; CT-LAC rg = 0.2055; CT-SCC-L rg = 0.3358; DHC-LAC rg = 0.3377). Genomic SEM supported a two-factor model (CFI > 0.99; SRMR = 0.0602) separating cancer outcomes (LAC β = 0.64, LC β = 1.10, SCC-L β = 0.83) from opioid traits (DHC β = 1.22; CT β = 0.61). MAGMA identified enrichment for oxidative phosphorylation/mitochondrial electron transport chain, Notch, cell-cycle, DNA damage response-p53/TP53, and immune pathways. Exploratory MR was feasible only for CT under the prespecified instrument-selection criteria, whereas DHC did not yield sufficient instruments and therefore could not be evaluated by MR. The CT-based MR analysis did not provide robust evidence for a causal effect of codeine/tramadol use liability on lung cancer outcomes, indicating that the observed LDSC associations are more appropriately interpreted as shared genetic liability rather than confirmed causality. Common-variant liability is broadly shared between opioid medication use and lung cancer, particularly CT-NSCLC, with a correlated two-factor structure separating cancer susceptibility from medication use. Enrichment analyses highlighted mitochondrial energetics, DNA damage response/TP53, immune signaling, and subtype-specific pathways. Exploratory MR was feasible only for CT and did not support a definitive causal interpretation, reinforcing the need to view the findings primarily as evidence of shared genetic liability.
Osteoarthritis (OA) is a chronic degenerative joint disease with a high global prevalence. It is characterized by cartilage degradation, synovial inflammation, and persistent joint pain, which substantially impair quality of life. Current therapies mainly alleviate symptoms rather than prevent or reverse structural joint damage. Although numerous OA-associated loci have been identified, most reside in noncoding regions, and their downstream effector genes and regulatory mechanisms remain incompletely understood. Therefore, clarifying how these variants influence gene expression is essential for prioritizing candidate genes and improving the molecular interpretation of OA susceptibility loci. Publicly available OA Genome-Wide Association Study (GWAS) summary statistics were integrated with Expression Quantitative Trait Locus (eQTL) data from the Genotype-Tissue Expression (GTEx) project. Cross-tissue and single-tissue transcriptome-wide association analyses were performed using UTMOST and FUSION, respectively. Candidate genes were then evaluated using COJO, MAGMA, Summary-databased Mendelian Randomization (SMR), Bayesian colocalization, and Mendelian Randomization (MR) analyses. GeneMANIA was used for network-based functional annotation, and Enrichr with the DSigDB library was used for compound-signature enrichment analysis. Cross-tissue TWAS identified 20 significant genes for knee OA and 12 for hip OA after FDR correction. Integration of UTMOST, FUSION, COJO, and MAGMA prioritized TACC3 and LTBP1 for knee OA and TMEM129 for hip OA. SMR, colocalization, and MR analyses provided additional but variable levels of statistical support across tissues. GeneMANIA indicated biologically relevant functional networks for LTBP1 and TACC3, whereas TMEM129 showed limited network enrichment. Enrichr/DSigDB analysis identified significant compound-signature enrichment terms overlapping the prioritized genes. These findings provide integrative statistical evidence linking OA-associated loci to gene regulation and prioritize TACC3, LTBP1, and TMEM129 as candidate genes associated with OA susceptibility. However, the strength of evidence differed across analytical frameworks, and the biological interpretation of tissue-specific signals remains to be validated in joint-relevant tissues and functional models. This study prioritized TACC3, LTBP1, and TMEM129 as candidate genes associated with OA susceptibility through integrated cross-tissue and single-tissue transcriptomic analyses. These findings improve the functional interpretation of OA GWAS loci and provide testable hypotheses for future validation in joint-relevant QTL datasets and experimental models.
Alzheimer's disease (AD), Parkinson's disease (PD) and Lewy body dementia (LBD) overlap clinically, pathologically and genetically, complicating interpretation of cross-disorder genome-wide association study (GWAS) signals. We analysed 322,963 UK Biobank participants with bidirectional time-varying Cox models, one-year and two-year lag analyses, and competing-risk sensitivity models to quantify AD-PD clinical co-occurrence. We then analysed European-ancestry AD, PD and LBD GWAS summary statistics using linkage disequilibrium score regression (LDSC), GCTA-mtCOJO/GSMR, MAGMA, stratified LDSC, brain eQTL/mQTL SMR with HEIDI filtering, and Bayesian colocalization for selected methylation probes. Conditional loci were compared with original GWAS loci to separate shared liability from retained disorder-predominant associations. PD was associated with subsequent AD (fully adjusted HR 2.27, 95% CI 1.94-2.65; P = 6.40E-25), and AD was associated with subsequent PD (HR 3.14, 95% CI 2.56-3.85; P = 2.10E-28). Lag and competing-risk sensitivity analyses remained concordant. LDSC estimated positive genetic correlations for AD-PD (rg = 0.20; P = 0.0086) and PD-LBD (rg = 0.61; P = 0.0005). Conditioning reduced genome-wide significant loci from 14 to 9 for AD, from 24 to 21 for PD and from 5 to 2 for LBD. Retained loci included AD signals near CR1, BIN1, CLU, SPI1, MS4A, PICALM, ABCA7 and APOE; PD signals near GBA, NUCKS1, TMEM163, STK39, GAK/TMEM175, BST1, SNCA, LRRK2, MAPT and RIT2; and LBD signals near SNCA/MMRN1 and APOE. MAGMA and S-LDSC highlighted amyloid, lipid, immune, synaptic-vesicle and brain-tissue enrichment patterns. Brain QTL analyses prioritized retained eQTL and mQTL signals, and colocalization supported shared PD-GWAS/mQTL signals at HLA-DRB5, ARHGAP27, CRHR1, MAPT and KANSL1. AD and PD show bidirectional clinical co-occurrence, whereas conditional genetic analyses retain a smaller set of disease-predominant loci and regulatory signals across AD, PD and LBD. These findings refine cross-disorder interpretation and nominate loci for independent genetic and functional validation.
The global distributions of volcanic eruption durations and of repose times between two eruptions have broad and heterogeneous shapes. Statistical analyses indicate that both distributions may exhibit a power-law tail for medium-to-long timescales. This scale-free behaviour could be symptomatic of volcanic systems that self-organize into a critical state. In this paper, we build on a former model for magma ascent through a pipe of stacked cells, which successfully reproduces the trend of the global distribution of volcanic eruption durations, but does not account for the inter-event times between eruptive episodes. By adapting and implementing this model within tree-like graphs instead of a linear structure, we are able to retain the behaviour of the eruption duration distribution, while obtaining a broad distribution for the repose times. In contrast with the pipe linear structure, the tree-like structure accounts for the fact that a large part of the magma that ascends through the crust does not reach the surface. This result highlights the importance of modelling volcanic plumbing systems as networks that reflect their complexity and variety.
Lower respiratory tract infections (LRTI), including pneumonia, tuberculosis, and COVID-19, share overlapping clinical features and risk factors, yet their common genetic architecture remains poorly understood. We applied genomic structural equation modeling (Genomic SEM) to dissect the shared genetic susceptibility among seven LRTI-related phenotypes using large-scale GWAS summary statistics. Multivariate GWAS (mvGWAS) was performed to identify variants associated with the latent LRTI factor. Post-GWAS analyses included Bayesian fine-mapping, transcriptome-wide association studies, MAGMA analysis, pathway enrichment, and cell-type specific heritability partitioning. A single latent factor model demonstrated excellent fit, confirming substantial genetic overlap across LRTI phenotypes. The mvGWAS identified 5,469 genome-wide significant variants, including 3,705 associations uniquely identified at the latent-factor level. Fine-mapping prioritized high-confidence causal variants at CAMK2D, NFKB1, CNTN5 and PARK2 loci, implicating calcium signaling, NF-κB-mediated inflammation, neuroimmune regulation, and mitochondrial quality control. TWAS highlighted TLK2, NUDT6, and PKN2 as key transcriptional regulators involved in chromatin homeostasis and inflammasome modulation. MAGMA identified RPL18A, HLA-DRB1, HLA-DQB1, and PTPN6, underscoring roles of ribosomal function, antigen presentation, and immune cell signaling. Pathway analysis revealed enrichment in coagulation cascades, while cell type analysis suggested involvement of hematopoietic progenitors and myeloid lineages. This study provides the first comprehensive genetic framework for shared LRTI susceptibility, revealing convergent biological pathways spanning inflammation, mitochondrial homeostasis, antigen presentation, and coagulation. These findings offer candidate targets for host-directed therapeutic strategies.
Genetic susceptibility to prostate cancer (PCa) varies across populations, yet East Asian men remain underrepresented in genome-wide association studies (GWAS). This study aimed to identify genetic variants associated with PCa in a Taiwanese cohort and to explore their potential biological relevance using integrative annotation approaches. We analyzed 961 PCa patients and 3792 age-matched controls from the Taiwan Biobank. Genotyping and imputation were performed using the Taiwan Biobank 2.0 array and the 1000 Genomes East Asian reference panel. Association testing was conducted using logistic regression adjusted for age and population structure. Gene-based analysis using Multi-marker Analysis of GenoMic Annotation (MAGMA), functional annotation using HaploReg, and prostate tissue cis-expression quantitative trait loci (cis-eQTL) and splicing QTL (sQTL) evaluation using the Genotype-Tissue Expression project (GTEx) were performed to explore functional relevance. We identified 371 genome-wide significant variants and 47 independent risk loci, including established regions (8q24.21, ZNF365, NCOR2, and PRKCB) as well as loci not previously reported in major GWAS (CCDC36, RAB6B, TTLL3, and PARD3B). MAGMA analysis identified 80 PCa-associated genes, and pathway analysis highlighted sphingolipid metabolism and leukocyte transendothelial migration. Integrative annotation indicated that several variants are located in regulatory elements and are associated with prostate-specific eQTL and sQTL effects. Additional analyses showed that several variants were associated with clinical indicators of disease aggressiveness, and age-stratified sensitivity analyses demonstrated consistent associations across age groups. Sensitivity analyses using alternative modeling approaches yielded comparable results. This study identifies both established and putatively novel genetic loci associated with PCa in a Taiwanese cohort and provides functional insights through integrative annotation. These findings contribute to understanding the genetic architecture of PCa in East Asian populations and highlight candidate loci that require independent validation in future studies.
Suicide is defined as an intentional act of ending one's own life. Suicide attempt (SA) is a significant risk factor for suicide death. Research on SA has progressed from socio-psychological perspectives to the molecular and genetic levels. While the biological mechanisms underlying genome-wide association studies (GWAS) identified risk loci remain largely unclear. To investigate the potential risk mechanisms, we constructed a systematic analytic pipeline using brain protein quantitative trait locus (pQTL) datasets (Banner, N=152; ROSMAP, N=376), a brain expression quantitative trait locus (eQTL) datasets (N=452), and SA GWAS summary statistics (Ncase=35,786, Ncontrol=779,392). We performed proteome-wide association study (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, transcriptome-wide association study (TWAS), and multi-marker analysis of genomic annotation (MAGMA) to systematically identify and screen for novel genetically supported candidate proteins related to the biological mechanism of SA in the brain. For functional annotation, we used the GeneMANIA to bulid a functional prediction network integrating co-expression, physical interactions, and pathway colocalization to identify core proteins. PWAS identified three brain proteins whose genetically predicted abundance was significantly associated with SA. Among them, GMPPB was prioritized as putative causal protein, supported by MR analysis (false discovery rate, FDR<0.05) and Bayesian colocalization analysis (posterior probability PPH4≥0.8). Specifically, higher genetically predicted GMPPB protein levels were associated with increased risk of SA. Although our analyses primarily relied on datasets from European-ancestry populations, the shared genetic architecture across populations and the generalizability of genome-wide data analytical approaches suggest that our findings may still provide useful insights into the biological mechanisms underlying SA and help inform the development of intervention strategies and genetic counseling in Chinese populations. 自杀是个体蓄意或自愿采取各种手段结束自己生命的行为。自杀未遂(suicide-attempts，SA)是自杀死亡的一个重要的预测因子，自杀未遂的研究已经从社会心理学层面深入到分子生物学和遗传学层面。尽管全基因组关联研究(genome-wide association study，GWAS)已鉴定出多个与自杀未遂相关的风险位点，但这些风险位点的潜在机制仍不清楚。为了探寻该病的潜在风险机制，本研究通过蛋白质数量性状位点(protein quantitative trait Locus，pQTL)数据集(Banner数据集N=152，ROSMAP数据集N=376)、表达数量性状位点(expression quantitative trait locus，eQTL)数据集(N=452)以及自杀未遂GWAS数据(病例组N=35,786，对照组N=779,392)，构建了一个系统性分析流程。该流程包括蛋白质组全关联研究(proteome-wide association study，PWAS)、孟德尔随机化(Mendeian randomization，MR)、贝叶斯共定位分析(Bayesian colocalization)、转录组全关联研究(transcriptome- wide association study，TWAS)和多基因关联分析(multi-marker analysis of genomic annotation，MAGMA)系统性分析流程，识别并筛选出与大脑中自杀未遂机制相关的新型遗传学支持的候选蛋白质。在功能注释层面，通过GeneMANIA分析平台实现功能预测网络，整合共表达、物理互作及通路共定位以识别核心蛋白质。通过PWAS分析，鉴定出3种大脑蛋白质的丰度变化与自杀未遂显著相关。其中，GMPPB被确立为自杀未遂的主要因果蛋白质，这一结论在孟德尔随机化分析(false discovery rate，FDR<0.05)和贝叶斯共定位分析中(后验概率posterior probability，PPH4≥0.8)得到了强有力的验证。具体而言，遗传预测较高的GMPPB表达与较高的自杀未遂的风险有关。本研究主要聚焦于欧洲人群的数据，但鉴于遗传背景的共通性及全基因组数据分析方法的普适性，其对探索中国人群自杀未遂的生理机制、制定有效干预措施及遗传咨询等方面也具有一定的参考和借鉴意义。.