Graphene-enhanced lateral photovoltaic effect observed in the Ag nanoparticle-covered graphene/n-type silicon.

Graphene is a kind of two-dimensional material with a single-layer carbon structure and has been investigated in many high-performance photodetectors. The lateral photovoltaic effect (LPE) is widely used in the position-sensitive detectors (PSDs) owing to its linear response of photovoltage to the light position. In this Letter, a type of graphene-enhanced LPE is observed in the Ag nanoparticle-covered graphene/n-type Si. The LPE sensitivity can reach 97.3 mV/mm, much higher than the sensitivity of 1.3 mV/mm in the control sample of Ag/Si and 5.2 mV/mm of graphene/Si. Based on the photocarriers' diffusion mechanism, tailoring a photocarrier transfer at the interface of a heterojunction plays a key role for the enhancement. These findings exhibit great application potential of graphene in the field of PSDs and offer an effective method for the optimization of LPE devices.

Multiple Sulfur Isotopic Evidence for Sulfate Formation in Haze Pollution.

The mechanism of sulfate formation during winter haze events in North China remains largely elusive. In this study, the multiple sulfur isotopic composition of sulfate in different grain-size aerosol fractions collected seasonally from sampling sites in rural, suburban, urban, industrial, and coastal areas of North China are used to constrain the mechanism of SO2 oxidation at different levels of air pollution. The Δ33S values of sulfate in aerosols show an obvious seasonal variation, except for those samples collected in the rural area. The positive Δ33S signatures (0‰ < Δ33S < 0.439‰) observed on clean days are mainly influenced by tropospheric SO2 oxidation and stratospheric SO2 photolysis. The negative Δ33S signatures (-0.236‰ < Δ33S < ∼0‰) observed during winter haze events (PM2.5 > 200 µg/m3) are mainly attributed to SO2 oxidation by H2O2 and transition metal ion catalysis (TMI) in the troposphere. These results reveal that both the H2O2 and TMI pathways play critical roles in sulfate formation during haze events in North China. Additionally, these new data provide evidence that the tropospheric oxidation of SO2 can produce significant negative Δ33S values in sulfate aerosols.

Constructing time-invariant dynamic surveillance rules for optimal monitoring schedules.

Dynamic surveillance rules (DSRs) are sequential surveillance decision rules informing monitoring schedules in clinical practice, which can adapt over time according to a patient's evolving characteristics. In many clinical applications, it is desirable to identify and implement optimal time-invariant DSRs, where the parameters indexing the decision rules are shared across different decision points. We propose a new criterion for DSRs that accounts for benefit-cost tradeoff during the course of disease surveillance. We develop two methods to estimate the time-invariant DSRs optimizing the proposed criterion, and establish asymptotic properties for the estimated parameters of biomarkers indexing the DSRs. The first approach estimates the optimal decision rules for each individual at every stage via regression modeling, and then estimates the time-invariant DSRs via a classification procedure with the estimated time-varying decision rules as the response. The second approach proceeds by optimizing a relaxation of the empirical objective, where a surrogate function is utilized to facilitate computation. Extensive simulation studies are conducted to demonstrate the superior performances of the proposed methods. The methods are further applied to the Canary Prostate Active Surveillance Study (PASS).

A Generalized Integration Approach to Association Analysis with Multi-category Outcome: An Application to a Tumor Sequencing Study of Colorectal Cancer and Smoking.

Cancer is a heterogeneous disease, and rapid progress in sequencing and -omics technologies has enabled researchers to characterize tumors comprehensively. This has stimulated an intensive interest in studying how risk factors are associated with various tumor heterogeneous features. The Cancer Prevention Study-II (CPS-II) cohort is one of the largest prospective studies, particularly valuable for elucidating associations between cancer and risk factors. In this paper, we investigate the association of smoking with novel colorectal tumor markers obtained from targeted sequencing. However, due to cost and logistic difficulties, only a limited number of tumors can be assayed, which limits our capability for studying these associations. Meanwhile, there are extensive studies for assessing the association of smoking with overall cancer risk and established colorectal tumor markers. Importantly, such summary information is readily available from the literature. By linking this summary information to parameters of interest with proper constraints, we develop a generalized integration approach for polytomous logistic regression model with outcome characterized by tumor features. The proposed approach gains the efficiency through maximizing the joint likelihood of individual-level tumor data and external summary information under the constraints that narrow the parameter searching space. We apply the proposed method to the CPS-II data and identify the association of smoking with colorectal cancer risk differing by the mutational status of APC and RNF43 genes, neither of which is identified by the conventional analysis of CPS-II individual data only. These results help better understand the role of smoking in the etiology of colorectal cancer.

Slight transition in Chinese atmospheric Pb isotopic fingerprinting due to increasing foreign Pb.

Atmospheric lead (Pb) pollution negatively affects human health and ecosystem, and extensive research is required to identify its sources and develop robust mitigation methods. In this study, the concentration and isotopic composition of Pb in fine particulate matter (PM2.5) at five sites in the China's Beijing-Tianjin-Hebei (BTH) region were analyzed. The results showed that the Pb concentration in the BTH region declined along the northwest direction in winter owing to the East Asian monsoon. Pb isotopic signatures confirmed that anthropogenic activities significantly contributed to Pb pollution, compared with natural sources. With the increasing import of foreign Pb (with a relatively lower 208Pb/206Pb ratio) to China, we hypothesized that the unique isotopic signature of Pb in Chinese aerosols may decline over time. Therefore, the application of the isotopic approach for quantifying Pb transported from China should be carefully appraised in future research to provide a realistic estimate of the contribution of local sources and the transboundary effect consistent with air mass trajectories analysis. This study provides a theoretical reference for supporting the utilization of Δ208Pb values for better clarify the transboundary impact of Pb pollution and to reduce international disputes.

Tracing the transboundary transport of atmospheric Particulate Bound Mercury driven by the East Asian monsoon.

Taking Beijing-Tianjin-Hebei (BTH) with severe atmospheric mercury (Hg) and PM2.5 pollution as a typical region, this study clarified the characteristics and transboundary transport of atmospheric Particulate Bound Mercury (PBM2.5) affected by the East Asian monsoon. Five sampling sites were conducted in rural, suburban, urban, industrial, and coastal areas of BTH from northwest to southeast along the East Asian monsoon direction. PBM2.5 showed increasing concentrations from northwest to southeast and negative δ202Hg values, indicating significant contributions from anthropogenic sources. However, the mean Δ199Hg values of PBM2.5 at the five sites were significantly positive, probably triggered by the photoreduction of Hg(II) during long-range transport driven by the East Asian monsoon. Apart from local anthropogenic emissions as the primary sources, the transboundary transport of PBM2.5, driven by west and northwest air masses originating in Central Asia and Russia, contributed significantly to the PBM2.5 pollution of BTH. Moreover, these air masses reaching BTH would carry elevated PBM2.5 concentrations further transported to the ocean by the East Asian monsoon. In contrast, the southeast air masses transported from the ocean by the East Asian monsoon in summer diluted inland PBM2.5 pollution. This study provides insight into the atmospheric Hg circulation affected by the East Asian monsoon.

The role of WSC domain-containing protein encoding gene AOL_s00043g401 in the growth and nematode trapping of Arthrobotrys oligospora.

Arthrobotrys oligospora is a model nematode-trapping fungus that has been extensively investigated to understand the interactions between fungi and nematodes. Nematode capture by A. oligospora is a complex process in which recognition of nematodes is generally believed to be mediated by lectins from the fungi. Lectins are a group of carbohydrate-binding proteins that widely exist in microorganisms and contain specific glycosylation recognition domains. In this work, we report the effect of a putative WSC domain-containing protein encoding gene AOL_s00043g401 (g401) on the growth and nematode-trapping of A. oligospora. The g401 gene was knocked out using the homologous recombination approach, and the △g401 mutant strain was then evaluated for its growth rate, conidial yield and germination rate, adaptation to environmental stresses, and nematocidal activity. Interestingly, the deletion of the putative lectin gene g401 had no significant effect on saprophytic growth, conidial yield and germination rate, responses to high salt, surfactant, and strong oxidative environments, as well as nematode-trapping efficiency of A. oligospora. We speculate that this phenomenon might have been caused by an intrinsic genetic compensation of the g401 in this fungus. For instance, more copies of WSC domain encoding genes or PQQ-DH domain encoding genes were found in the genome of A. oligospora. These findings provide further experimental evidence on the effect of lectin-related functional proteins in A. oligospora on nematode capture and will help further analyze their potential roles in the biological control of nematodes in the future.

Genetic Regulation of DNA Methylation Yields Novel Discoveries in GWAS of Colorectal Cancer.

BACKGROUND: Colorectal cancer has a strong epigenetic component that is accompanied by frequent DNA methylation (DNAm) alterations in addition to heritable genetic risk. It is of interest to understand the interrelationship of germline genetics, DNAm, and colorectal cancer risk. METHODS: We performed a genome-wide methylation quantitative trait locus (meQTL) analysis in 1,355 people, assessing the pairwise associations between genetic variants and lymphocytes methylation data. In addition, we used penalized regression with cis-genetic variants ± 1 Mb of methylation to identify genome-wide heritable DNAm. We evaluated the association of genetically predicted methylation with colorectal cancer risk based on genome-wide association studies (GWAS) of over 125,000 cases and controls using the multivariate sMiST as well as univariately via examination of marginal association with colorectal cancer risk. RESULTS: Of the 142 known colorectal cancer GWAS loci, 47 were identified as meQTLs. We identified four novel colorectal cancer-associated loci (NID2, ATXN10, KLHDC10, and CEP41) that reside over 1 Mb outside of known colorectal cancer loci and 10 secondary signals within 1 Mb of known loci. CONCLUSIONS: Leveraging information of DNAm regulation into genetic association of colorectal cancer risk reveals novel pathways in colorectal cancer tumorigenesis. Our summary statistics-based framework sMiST provides a powerful approach by combining information from the effect through methylation and residual direct effects of the meQTLs on disease risk. Further validation and functional follow-up of these novel pathways are needed. IMPACT: Using genotype, DNAm, and GWAS, we identified four new colorectal cancer risk loci. We studied the landscape of genetic regulation of DNAm via single-SNP and multi-SNP meQTL analyses.

The fucose-specific lectin gene AOL_s00054g276 affects trap formation and nematocidal activity of the nematophagous fungus Arthrobotrys oligospora.

Nematode-trapping fungi are natural enemies of nematodes in nature. Arthrobotrys oligospora, a typical nematode-trapping fungus with a clear genetic background, can capture and infect nematodes by forming adhesive three-dimensional networks. Lectins, a class of glycoproteins containing glycosyl-specific recognition domains, play an important role in biological recognition. However, the fucose-specific lectins have rarely been studied regarding the process of preying on nematodes. In this study, we characterized the biological role of the fucose-specific lectin-encoding gene AOL_s00054g276 (g276) in A. oligospora. The gene g276 was first deleted based on homologous recombination, then the phenotype and nematocidal activity of the Δg276 mutant was evaluated. The results showed that the deletion of gene g276 delayed trap formation and weakened its nematocidal activity; however, mycelial growth, conidia production, conidial germination rates and adaption to environmental stresses were not affected. Our results suggest that the fucose-specific lectin-encoding gene g276 might be associated with the morphogenesis of this fungus, and its deletion resulted in a significantly low density of three-dimensional traps (P < 0.05) and a significantly low nematode-trapping efficiency (P < 0.001). These findings provide a basis for further elucidating the mechanism of A. oligospora preying on nematodes and lay a foundation for the development and utilization of fungal-derived lectins for nematode control in the future.

A putative F-box-domain-encoding gene AOL_s00076g207 regulates the development and pathogenicity of Arthrobotrys oligospora.

F-box protein is a key component of the Skp1-cullin-F-box-type ubiquitin ligase complex (SCF-ULC) that marks its target proteins with ubiquitin for proteasomal degradation. In this study, we explored the potential role of AOL_s00076g207 (Aog207) in Arthrobotrys oligospora, a model fungus for studying nematodes-fungi interactions. The Aog207 gene encodes a putative F-box protein of the SCF-ULC. Deletion of Aog207 could inhibit mycelial growth in TYGA and PDA media. More importantly, the conidial germination rate of ΔAog207 mutants was remarkably declined compared to that of wild-type (WT) strain, and the mutant strains were more sensitive toward chemical stressors than the WT strain. In addition, ΔAog207 mutants generated fewer traps and captured fewer nematodes than WT strain. In summary, Aog207 disruption significantly affected the pathogenicity, mycelial growth, conidial germination, environmental adaptation and trap formation of A. oligospora. These findings may facilitate a better understanding of the nematode predation mechanism of A. oligospora and provide an experimental basis for developing biological control agents against nematodes.

High-Sensitivity Infrared Photoelectric Detection Based on WS2 /Si Structure Tuned by Ferroelectrics.

As one of the typical transition-metal dichalcogenides with distinct optical and electrical properties, WS2 exhibits tremendous potential for optoelectronic devices. However, its inherent band gap range limits the application in the infrared region. To overcome this draw-back and improve the sensitivity, P(VDF-CTFE) is used as a ferroelectric gate to control the states of WS2 /Si junctions and achieve an enhanced infrared photodetection. The polarization electric field not only broadens the range of absorption wavelength (405-1550 nm) but also greatly promotes the sensitivity of lateral photovoltaic effect (LPE) (from 198.6 to 503.2 mV mm-1 ). This phenomenon is attributed to the reduction of WS2 band gap and the change of potential barrier at the interface of the junction. Meanwhile, the response speed is improved significantly due to the increase of carrier initial kinetic energy. This new scheme for ferroelectric tuned LPE opens up a way to realize high-sensitivity, ultrafast, and stable infrared photodetection.

Recent Research Advances in Plasma Spraying of Bulk-Like Dense Metal Coatings with Metallurgically Bonded Lamellae.

Although thermal spray metallic coatings have been widely used for materials protection from wear, corrosion and oxidation, its porous feature limits the full utilization of materials potential. Moreover, the oxidation inherent to thermal spraying in the ambient atmosphere is detrimental to interlamellar bonding formation, which further degrades the performance of thermal spray metal coatings. How to tape out the full potential of spray materials in the form of the coating is a still great challenge to thermal spray coating technology. Facing such challenge, recent efforts have been made to deposit dense metallic coatings with sufficiently bonded lamellae by oxide-free molten droplets through atmospheric plasma spraying. In this paper, the strategies for depositing bulk-like metal coatings will be reviewed. The formation of the bulk-like coating through post-spray treatments is briefly reviewed including post-spray heat treatment and laser remelting following the brief introduction to the features of thermal spray metallic coatings. The effect of the substrate preheating temperature on the splat formation and subsequently the adhesion formation was examined to reveal the dominant limitation of resultant oxide scale. Then, the role of the deposition temperature on the formation of bulk-like metal deposits with neglecting the effect of oxidation during spraying by vacuum plasma spraying practices is shortly presented. The recent progress on the new strategies to develop spread-fusing bonding mechanism and in-situ in-flight deoxidizing mechanism through developing ultra-hot metallic droplets will be introduced. The thermodynamics and kinetics requirements for the in-situ in-flight deoxidizing through deoxidizer elements adding to alloy spray powders for achieving oxide-free molten droplets in the ambient atmosphere are examined. The conditions to develop the spread-fusing mechanism during the spreading of impacting molten metal droplet for metallurgical bonding are presented. It is obvious from this review paper that the realization of two mechanisms depends on both the spray materials design and heating control of in-flight particles. Through the generation of ultra-hot droplets by plasma spraying to achieve oxide-free molten droplets, strategically it will be possible to deposit bulk-like dense metallic coating through spread-fusing of splat surfaces with limited post-spray oxidation. Such strategies will tape out the full potential of coating materials and open up the new application fields for plasma spraying.

The isotopic patterns and source apportionment of nitrate and ammonium in atmospheric aerosol.

Nitrate (NO3-) and ammonium (NH4+) are the major components in inorganic aerosol. However, their sources and formation processes remain unclear. This study conducted a year-round field measurement of TSP, PM2.5 and PM1.0 in five different sites in the Beijing-Tianjin-Hebei (BTH) region to determine the concentrations of water-soluble inorganic ions (WSIIs) and the isotopic compositions of inorganic nitrogen (δ15N-NH4+, δ15N-NO3-, and δ18O-NO3-). The results showed the highest concentration of WSIIs in winter and lowest in summer. δ15N-NO3-, δ18O-NO3-, and δ15N-NH4+ were in the range of -6.1-18.2, 52.2-103.8, and -28.7-36.2‰, respectively. The seasonal variations of δ15N-NO3- and δ15N-NH4+ were an indication of relative contributions of the main sources and effects of meteorological conditions. The source apportionment identified fossil fuel combustion (38.2-50.6%), agricultural emissions (18-24.7%), biomass burning (16.3-22.7%), and road dust/soil (8.7-23.4%) were the main sources of inorganic aerosols. The local sources and regional migration contributed to the level of inorganic aerosol pollution. In winter, the aerosol in the BTH region was affected by the air mass from the northwest. While in spring and summer, the air mass was mainly from the South China. The low temperature and high relative humidity favored to the formation of inorganic nitrogen aerosol, and solar radiation affected the formation processes of inorganic aerosols by changing the oxidation pathway of NO3- and accelerating the volatilization and dissociation of ammonium nitrate (NH4NO3). This study discovered the main source contributions of inorganic nitrogen aerosol using N and O isotopes composition, and the obtained information has a great importance in understanding the effects of meteorological conditions on formation and the contribution of regional transport.

High performance and low power consumption resistive random access memory with Ag/Fe2O3/Pt structure.

Due to magnetic field tunability and the abundance of iron in the Earth's crust, iron oxide-based resistive random access memory (RRAM) is considered to be low cost and potential for multi-level storage. However, the relatively high operation voltage (>1 V) and small storage window (<100) limit its application. In this work, the devices with simple Ag/Fe2O3/Pt structure exhibit typical bipolar resistive switching with ultralow set voltage (Vset) of 0.16 V, ultralow reset voltage (Vreset) of -0.04 V, high OFF/ON resistance ratio of 103, excellent cycling endurance more than 104and good retention time longer than 104s. Each major parameter has about an order of magnitude improvement compared to the previous data. The devices demonstrate outstanding stable low power consumption quality. Based on the analysis of the experimental results, a percolation model of silver ion migration was established and confirmed that low operation voltage is attributed to the amorphous oxide layer with large porosity. During electrical testing, the compliance current (Ic) and maximum reset voltage (Vmax) can also affect the device performance. This discovery suggests Fe2O3memristor has significant potential for application and provides a new idea for the realization of high-performance low-power RRAM.

Genetic variants associated with cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Human cytomegalovirus (CMV) reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Despite routine screening for CMV reactivation and early antiviral treatment, the rates of CMV-related complications after HCT remain high. Genetic variants in both the donor and recipient have been associated with the risk of CMV reactivation and disease after HCT, but these associations have not been validated, and their clinical importance remains unclear. In this study, we assessed 117 candidate variants previously associated with CMV-related phenotypes for association with CMV reactivation and disease in a cohort of 2169 CMV-seropositive HCT recipients. We also carried out a genome-wide association study (GWAS) for CMV reactivation and disease in the same cohort. Both analyses used a prespecified discovery and replication approach to control the risk of false-positive results. Among the 117 candidate variants, our analysis implicates only the donor ABCB1 rs1045642 genotype as a risk factor for CMV reactivation. This synonymous variant in P-glycoprotein may influence the risk of CMV reactivation by altering the efflux of cyclosporine and tacrolimus from donor lymphocytes. In the GWAS analysis, the donor CDC42EP3 rs11686168 genotype approached the significance threshold for association with CMV reactivation, although we could not identify a mechanism to explain this association. The results of this study suggest that most genomic variants previously associated with CMV phenotypes do not significantly alter the risk for CMV reactivation or disease after HCT.

The role of Jacalin-related lectin gene AOL_s00083g511 in the development and pathogenicity of the nematophagous fungus Arthrobotrys oligospora.

Arthrobotrys oligospora is a model species of nematophagous fungi and has great potential for the biological control of nematode diseases. Lectin is a protein that binds to carbohydrates and their complexes with high specificity, which mediates recognition events in various physiological and pathological processes. This study aimed to investigate the role of the Jacalin-related lectin (JRL) gene, AOL_s00083g511, in A. oligospora development. Through a homology recombination approach, we obtained the AOL_s00083g511 knockout mutant strain (Ag511). Next, the biological characteristics of the Ag511 mutant strain, including growth rate, conidia germination rate, adaptation to environmental stresses, and nematocidal activity, were compared with those of the wild-type (WT) strain. The results showed that the JRL gene AOL_s00083g511 did not affect fungal growth, conidia germination, 3D-trap formation, and the ability of A. oligospora to prey on nematodes significantly. We speculate that this phenomenon may be caused by a loss of the key ß1-ß2 loops in the AOL_ s00083g511-encoded JRL domain and an intrinsic genetic compensation of AOL_s00083g511 in this fungus. The growth rates of both strains on high salt or surfactant media were similar; however, in the strong oxidation medium, the growth rate of the Ag511 mutant was significantly lower than that of the WT strain, indicating that AOL_s00083g511 might play a role in oxidative stress resistance. These findings provide a basis for further analysis of the related functions of the JRL gene in A. oligospora and their potential roles in the biological control of nematodes in the future.

Heterojunction interface-induced enhancement of position-sensitive photodetection in the nano-film of Ti/SrTiO3 based on the p-type silicon.

Complex oxide perovskites exhibit a range of novel, to the best of our knowledge, physical phenomena and have gained popularity as a material system in the past decades. Strontium titanate (SrTiO3) is an iconic material among oxide perovskite due to its unusual electronic transport behavior and has been investigated in many electronic devices. In this Letter, a type of SrTiO3 nano-film-induced enhancement of lateral photovoltaic effect (LPE) is observed in the heterojunction of Ti/SrTiO3/p-type Si. Optimizing the thickness of SrTiO3, the LPE sensitivity can reach 123.2 mV/mm, which is much higher than the sensitivity in the control samples of Ti/Si (55.3 mV/mm) and SrTiO3/Si (∼0mV/mm). These findings offer an effective way to improve the sensitivity and will be helpful in the development of oxide-based photodetection devices.

Atmospheric lead pollution in a typical megacity: Evidence from lead isotopes.

Atmospheric lead (Pb) pollution has adverse health effects on humans, while the sources and atmospheric process of Pb are key scientific problems. In this study, the concentrations and isotopic composition of Pb in fine particulate matter (PM2.5), coal and street dust samples collected from a typical megacity Beijing were analyzed to identify the sources of atmospheric Pb. Results showed that the Pb concentrations in PM2.5 were high in winter (168.1 ± 32.0 ng/m3) and low in summer (27.7 ± 9.1 ng/m3), whereas Pb isotopic values presented opposite variation trends. The abnormally elevated Pb concentrations in winter were probably related to coal combustion, while declined Pb concentration in summer may be attributed to favorable meteorological parameters such as high temperature, high wind speed, and frequent rain events. Pb isotopic ratios indicated that anthropogenic sources (coal combustion and vehicle exhaust) and natural sources were the main contributors to Pb in PM2.5. Combined with the binary model, the anthropogenic sources predominantly contributed to Pb in the Beijing atmosphere by approximately 85% annually, while the natural sources accounted for the rest of 15%. More specifically, the contribution of natural sources was about 9.4% in spring, 29.7% in summer, 16.0% in autumn and 6.1% in winter, suggesting that natural sources might contribute more lead into the atmosphere during clear days. Furthermore, the contribution of the vehicle exhaust to atmospheric Pb was nonnegligible in megacity, highlighting that the ownership of motor vehicles in megacity should be regulated and more efforts should be paid to strengthen vehicle emission standard. This study may enrich the reservoir of Pb isotopic composition in nature and provides a new method to investigate the Pb migration and transformation in the environment, and also serve as a theoretical reference for pollution control measures.

A general framework for functionally informed set-based analysis: Application to a large-scale colorectal cancer study.

Genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants associated with various phenotypes, but together they explain only a fraction of heritability, suggesting many variants have yet to be discovered. Recently it has been recognized that incorporating functional information of genetic variants can improve power for identifying novel loci. For example, S-PrediXcan and TWAS tested the association of predicted gene expression with phenotypes based on GWAS summary statistics by leveraging the information on genetic regulation of gene expression and found many novel loci. However, as genetic variants may have effects on more than one gene and through different mechanisms, these methods likely only capture part of the total effects of these variants. In this paper, we propose a summary statistics-based mixed effects score test (sMiST) that tests for the total effect of both the effect of the mediator by imputing genetically predicted gene expression, like S-PrediXcan and TWAS, and the direct effects of individual variants. It allows for multiple functional annotations and multiple genetically predicted mediators. It can also perform conditional association analysis while adjusting for other genetic variants (e.g., known loci for the phenotype). Extensive simulation and real data analyses demonstrate that sMiST yields p-values that agree well with those obtained from individual level data but with substantively improved computational speed. Importantly, a broad application of sMiST to GWAS is possible, as only summary statistics of genetic variant associations are required. We apply sMiST to a large-scale GWAS of colorectal cancer using summary statistics from ∼120, 000 study participants and gene expression data from the Genotype-Tissue Expression (GTEx) project. We identify several novel and secondary independent genetic loci.

Recipient and donor genetic variants associated with mortality after allogeneic hematopoietic cell transplantation.

Many studies have suggested that genetic variants in donors and recipients are associated with survival-related outcomes after allogeneic hematopoietic cell transplantation (HCT), but these results have not been confirmed. Therefore, the utility of testing genetic variants in donors and recipients for risk stratification or understanding mechanisms leading to mortality after HCT has not been established. We tested 122 recipient and donor candidate variants for association with nonrelapse mortality (NRM) and relapse mortality (RM) in a cohort of 2560 HCT recipients of European ancestry with related or unrelated donors. Associations discovered in this cohort were tested for replication in a separate cohort of 1710 HCT recipients. We found that the donor rs1051792 A allele in MICA was associated with a lower risk of NRM. Donor and recipient rs1051792 genotypes were highly correlated, making it statistically impossible to determine whether the donor or recipient genotype accounted for the association. Risks of grade 3 to 4 graft-versus-host disease (GVHD) and NRM in patients with grades 3 to 4 GVHD were lower with donor MICA-129Met but not with MICA-129Val, implicating MICA-129Met in the donor as an explanation for the decreased risk of NRM after HCT. Our analysis of candidate variants did not show any other association with NRM or RM. A genome-wide association study did not identify any other variants associated with NRM or RM.