Controllable Fabrication of Vertical Graphene with Tunable Growth Nature by Remote Plasma-Enhanced Chemical Vapor Deposition.

As an important member of the graphene family, vertical graphene (VG) has broad applications like field emission, energy storage, and sensors owing to its fascinating physical and chemical properties. Among various fabrication methods for VG, plasma enhanced chemical vapor deposition (PECVD) is most employed because of the fast growth rate at relatively low temperature for the high-quality VG. However, to date, relations between growth manner of VG and growth parameters such as growth temperature, dosage of gaseous carbon source, and electric power to generate plasma are still less known, which in turn hinder the massive production of VG for further applications. In this study, the growth behavior of VG was studied as functions of temperature, plasma power, and gas composition (or chamber pressure). It was found that the growth behavior of VG is sensitive to the growth conditions mentioned above. Although conditions with high growth temperature, large flow rate of mixed gas of methane and carrier gases, and high plasma power may be helpful for the fast growth of VG, brunching of VG is simultaneously enhanced, which in turn decreases the vertical growth nature of VG. High-quality VG can be achieved by optimizing the growth parameters. It was revealed that the vertical growth nature of VG is governed by the electric field at the interfacial layer between VG and the substrate, for which its strength is influenced by the density of plasma. These findings are important for the general understanding of the VG growth and provided a feasible way for the controllable fabrication of VG using the remote PECVD method which is usually believed to be unsuitable for the fabrication of VG.

Expression and immunogenicity of recombinant porcine epidemic diarrhea virus Nsp9.

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, which leads to significant economic losses. Coronavirus nonstructural protein 9 (Nsp9) is an essential RNA binding protein for coronavirus replication, which renders it a promising candidate for developing antiviral drugs and diagnosis targeting PEDV. In this study, PEDV Nsp9 protein fused with MBP protein and His-tag were expressed and purified in Escherichia coli. Furthermore, immunization of MBP-Nsp9 enhances both humoral and cellular immunity responses as compared with that of His-Nsp9 protein. Finally, the swine immunization showed that Nsp9 protein could stimulate the swine immunity system to carry out humoral immunity, and the generated antibody could inhibit the proliferation of PEDV in Vero cells. Altogether, our data provide direct evidence for the immunogenicity of PEDV Nsp9, which sheds light on the future developments of anti-PEDV drugs and vaccines for PED prevention.

Kilogram-scale fabrication of TiO2 nanoparticles modified with carbon dots with enhanced visible-light photocatalytic activity.

Incorrect discharge of dye wastewater will cause environment pollution and be very harmful to human health. Visible-light photocatalysis over large-scale synthesized semiconductor materials can become one of the feasible solutions for the practical application of purifying dye wastewater. As a new candidate, carbon dots (CDs) with unique fluorescence were fabricated on a tens of grams scale and then further applied to the kilogram-scale synthesis of a CDs/TiO2 composite by one-step heat treatment. Compared with single TiO2 nanoparticles (NPs), the CDs/TiO2 composite with a large specific surface area exhibits enhanced photo-degradation performance for methyl orange (MO). This phenomenon can be attributed to the loading of CDs in the TiO2 NPs, which is conducive to broadening the light absorption spectrum and improving absorption intensity, narrowing the band gap, charge carrier trapping, up-converting properties, and charge separation. The kilogram-scale synthesis of the CDs/TiO2 photocatalyst does not affect the morphology, structure, optical properties and photocatalytic performance of the composite, which opens up a new avenue to construct elaborate heterostructures for enhanced photocatalytic performance using visible light as the light source.

Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aß) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; ß = 0.35, SE = 0.01, P = 6.2 × 10-311, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; ß = 0.07, SE = 0.01, P = 9.2 × 10-09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; ß = 0.1, SE = 0.02, P = 2.4 × 10-10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; ß = 0.16, SE = 0.03, P = 1.1 × 10-09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, ß = 0.79, SE = 0.14, P = 1.4 × 10-08, MAF = 0.006, sex-interaction P = 9.8 × 10-07) and chr11p.15.2 (rs192346166, ß = 0.94, SE = 0.17, P = 3.7 × 10-08, MAF = 0.004, sex-interaction P = 1.3 × 10-03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.

ZnO Nanoparticles Modified by Carbon Quantum Dots for the Photocatalytic Removal of Synthetic Pigment Pollutants.

Synthetic pigment pollutants caused by the rapid development of the modern food industry have become a serious threat to people's health and quality of life. Environmentally friendly ZnO-based photocatalytic degradation exhibits satisfactory efficiency, but some shortcomings of large band gap and rapid charge recombination reduce the removal of synthetic pigment pollutants. Here, carbon quantum dots (CQDs) with unique up-conversion luminescence were applied to decorate ZnO nanoparticles to effectively construct the CQDs/ZnO composites via a facile and efficient route. The ZnO nanoparticles with a spherical-like shape obtained from a zinc-based metal organic framework (zeolitic imidazolate framework-8, ZIF-8) were coated by uniformly dispersive quantum dots. Compared with single ZnO particles, the obtained CQDs/ZnO composites exhibit enhanced light absorption capacity, decreased photoluminescence (PL) intensity, and improved visible-light degradation for rhodamine B (RhB) with the large apparent rate constant (k app). The largest k app value in the CQDs/ZnO composite obtained from 75 mg of ZnO nanoparticles and 12.5 mL of the CQDs solution (∼1 mg·mL-1) was 2.6 times that in ZnO nanoparticles. This phenomenon may be attributed to the introduction of CQDs, leading to the narrowed band gap, an extended lifetime, and the charge separation. This work provides an economical and clean strategy to design visible-light-responsive ZnO-based photocatalysts, which is expected to be used for the removal of synthetic pigment pollutants in food industry.

NiO/g-C3N4 composite for enhanced photocatalytic properties in the wastewater treatment.

The massive discharge of colored wastewater has seriously harmed the environment and people's health. Photocatalysis technology is an effective method to purify colored wastewater and has been widely concerned in colored wastewater treatment. In this study, based on the obtained nickel oxide (NiO) nanospheres by solvothermal method and graphite phase carbon nitride (g-C3N4) nanosheets by thermal polymerization method, the p-n heterojunction composed of NiO nanospheres and g-C3N4 nanosheets was successfully constructed by heat treatment for the photocatalytic degradation of methyl orange (MO). The morphology, crystallinity, surface features, and optical properties of the NiO/g-C3N4 composites were investigated by various characterization methods such as scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FT-IR), X-ray photoelectron spectroscopy (XPS), UV-vis spectrophotometer, and fluorescence spectrometer (PL), which provided the evidence for the formation of the heterojunction between NiO and g-C3N4. Compared with the g-C3N4 nanosheets and NiO nanospheres, the NiO/g-C3N4 composites showed the improved photocatalytic activity for the degradation of MO under visible light irradiation. And the NiO/g-C3N4 composite with the mole ratio of NiO and g-C3N4 of 2:8 displayed the best photocatalytic activity of MO, and more than 90% of MO can be degraded under the illumination of 100 min. The high photocatalytic properties over the NiO/g-C3N4 composite may be due to high specific surface area, the perfect band matching, and the formation of the p-n heterojunction, which helps to promote interfacial charge transfer and hinder the recombination of photo-generated electrons and holes. Moreover, the NiO/g-C3N4 composite exhibits the universality and cyclic stability, which is expected to have broad application prospects in the treatment of colored wastewater.

Reduced binding activity of vaccine serum to omicron receptor-binding domain.

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

Rainstorm Disaster Risk Assessment and Influence Factors Analysis in the Yangtze River Delta, China.

Rainstorm disasters have had a serious impact on the sustainable development of society and the economy. However, due to the complexity of rainstorm disasters, it is difficult to measure the importance of each indicator. In this paper, the rainstorm disaster risk assessment framework was systematically proposed based on the disaster system theory and a system of corresponding indicators was established. Furthermore, the genetic algorithm optimized projection pursuit and XGBoost were coupled to assess the rainstorm disaster risk and to measure the relative importance of each indicator. Finally, the Yangtze River Delta was taken as the case study area. The results show that: the rainstorm disaster risk in the eastern and southeast is higher than those in the central and northwest of the Yangtze River Delta; the total precipitation from June to September and the top ten indicators contribute 9.34% and 74.20% to the rainstorm disaster risk assessment results, respectively. The results can provide references for decision makers and are helpful for the formulation of rainstorm adaptation strategies.

Boosted Inner Surface Charge Transfer in Perovskite Nanodots@Mesoporous Titania Frameworks for Efficient and Selective Photocatalytic CO2 Reduction to Methane.

Exploring high-efficiency and stable halide perovskite-based photocatalysts for the selective reduction of CO2 to methane is a challenge because of the intrinsic photo- and chemical instability of halide perovskites. In this study, halide perovskites (Cs3 Bi2 Br9 and Cs2 AgBiBr6 ) were grown in situ in mesoporous TiO2 frameworks for an efficient CO2 reduction. Benchmarked CH4 production rates of 32.9 and 24.2 µmol g-1 h-1 with selectivities of 88.7 % and 84.2 %, were achieved, respectively, which are better than most reported halide perovskite photocatalysts. Focused ion-beam sliced-imaging techniques were used to directly image the hyperdispersed perovskite nanodots confined in mesopores with tunable sizes ranging from 3.8 to 9.9 nm. In situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy showed that the built-in electric field between the perovskite nanodots and mesoporous titania channels efficiently promoted photo-induced charge transfer. Density functional theory calculations indicate that the high methane selectivity was attributed to the Bi-adsorption-mediated hydrogenation of *CO to *HCO that dominates CO desorption.

Development of fluorescence sensor and test paper based on molecularly imprinted carbon quantum dots for spiked detection of domoic acid in shellfish and lake water.

Excessive levels of domoic acid (DA) in edible shellfish and water can seriously threaten human health and even cause death. Herein, we have developed a fluorescence sensor and test paper based on molecularly imprinted carbon quantum dots (B-CDs@MIPs) for DA analysis. In this research, the prepared carbon quantum dots (B-CDs) with good optical properties were used as the sensitive fluorescent signal probes, and the molecularly imprinted polymers (MIPs) instead of biological antibodies were employed as the specific recognition components because of their high stability and low cost. Due to the shielding effect of imprinted silicon layer and the influence of modified groups introduced in the MIPs preparation process, the fluorescence signal of B-CDs in MIPs is inhibited. Interestingly, the DA can cause the partial recovery of the fluorescence intensity of B-CDs@MIPs by passivating the modified groups on the surface of B-CDs in MIPs. According to this principle, the designed fluorescence sensor reveals outstanding stability, super anti-interference ability, and excellent sensitivity, with the detection limit down to 10 nM. The sensor has been successfully applied to the rapid and accurate spiked analysis of DA in edible shellfish and lake water, providing excellent recoveries. More importantly, the designed inexpensive and easy-to-operate fluorescent test paper can realize preliminary qualitative analysis of DA on site by naked eye, indicating its promising application potential in food and environmental analysis.

Adsorption Behavior of Magnetic Carbon-Supported Metal Nickel for the Efficient Dye Removal from Water.

Magnetic carbon-supported metal nickel has been successfully synthesized by solvothermal method and heat treatment for highly effective adsorption of various reactive dyes. Structure characterization and composition analysis demonstrated that the metal nickel nanoparticles with the size of 1-2 nm were embedded into the pore of carbon spheres. It is helpful to prevent the agglomeration and falling off of metal nickel nanoparticles on the surface of carbon spheres. The adsorption performance of the carbon-supported metal nickel nanospheres for reactive brilliant yellow R-4GLN was studied by changing the pH value and initial concentration of the solution, adsorption time, adsorption temperature, and the amount of adsorbent. The carbon-supported metal nickel showed fast and efficient adsorption activity. After 5 min of adsorption, the removal efficiency of 10 mL 25 mg·mL-1 reactive brilliant yellow R-4GLN was close to 100%. The carbon-supported metal nickel composite was reused 20 times, and the removal efficiency of dye remained above 98%. It also showed good adsorption performance on various reactive dyes with wide universality, which has a certain adsorption effect on most dyes with a high utilization value in wastewater treatment.

On the Coupling and Coordination Development between Environment and Economy: A Case Study in the Yangtze River Delta of China.

The coupling and coordination development of the environment and economy (CC2E) is one of the most vital issues to sustainable development. This paper adopted the coupling coordination model, projection pursuit algorithm, and random forest model to explore the spatial-temporal evolution and influencing factors of the CC2E in the Yangtze River Delta from 2015 to 2019, respectively. The results showed that: (1) The degree of coupling coordination (DCC) of the CC2E in most cities of the Yangtze River Delta has risen from primary coordination to intermediate coordination. (2) In the spatial perspective, the distribution of DCC is correlated with geographical location. The value of DCC in the western region was significantly lower than that of the eastern cities. (3) The influencing factors results showed that the GDP in the economic subsystem and the annual average concentration of PM2.5 in the environmental subsystem were the most influencing factors of DCC in the Yangtze River Delta. The established index system of CC2E and the measurements of CC2E provide a new idea for how to achieve sustainable development. Meanwhile, this study can provide recommendations for formulating the environmental protection and economic development policy.

Rapid electrochemical detection of domoic acid based on polydopamine/reduced graphene oxide coupled with in-situ imprinted polyacrylamide.

Domoic acid, namely amnesic shellfish toxin, is a highly neurotoxic substance to marine animals and humankind. To reduce the incidence of poisoning accidents, the exploitation of specific and rapid detection method for domoic acid monitoring is highly required. Herein, an electrochemical molecularly imprinted polymer (MIP) sensor based on polydopamine-reduced graphene oxide/polyacrylamide composite (PDA-rGO/PAM) was constructed successfully to detect domoic acid. The domoic acid molecule could be recognized in imprinted cavities of PAM reversibly through hydrogen bonding. PDA-rGO promoted the loading capacity of PAM and improved the charge transfer rate, which amplified the electrical signal response of the MIP sensor. The screen-printed electrode (SPE) modified with PDA-rGO/PAM displayed satisfactory response toward toxin contaminated sample at a linear range from 1 to 600 nM and a low detection limit of 0.31 nM, demonstrating the prospective application of the transducer as a portable sensing platform for the on-site detection of hazardous marine biotoxin. Moreover, benefiting from the superior specificity and stability of MIP, the fabricated sensor could be utilized to detect the domoic acid content in mussel extracts directly without complex pretreatment operation.

Dual-Targeting Nanoprobe for Early Diagnosis of Pheochromocytoma Though Coinstantaneous Identification of Circulating Tumor Cells.

Circulating tumor cells (CTCs) play a pivotal role in the early diagnosis of pheochromocytoma (PCC). Herein, we fabricated a new dual-targeting nanoprobe for coinstantaneous identification of rare PCC-CTCs from peripheral blood via targeting the norepinephrine transporter (NET) and somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. Meta-iodobenzylguanidine (MIBG) functionalized magnetic Fe3O4 and octreotide (DOTA) decorated signal amplification Ag@SiO2 nanosphere were used to capture and detect PCC-CTCs by binding to NET and SSTR2. The proposed dual-targeting sensor achieved good reproducibility and high sensitivity for the monitoring of PC12 in the concentration range from 5 to 5 × 104 cells mL-1, with detection limits of 2 cell/mL. This strategy opens a new approach for simple, sensitive, and rapid determination of PCC biomarkers, which shows great potential in early diagnosis, prognosis, and therapeutic evaluation of PCC.

Assessing non-Mendelian inheritance in inherited axonopathies.

PURPOSE: Inherited axonopathies (IA) are rare, clinically and genetically heterogeneous diseases that lead to length-dependent degeneration of the long axons in central (hereditary spastic paraplegia [HSP]) and peripheral (Charcot-Marie-Tooth type 2 [CMT2]) nervous systems. Mendelian high-penetrance alleles in over 100 different genes have been shown to cause IA; however, about 50% of IA cases do not receive a genetic diagnosis. A more comprehensive spectrum of causative genes and alleles is warranted, including causative and risk alleles, as well as oligogenic multilocus inheritance. METHODS: Through international collaboration, IA exome studies are beginning to be sufficiently powered to perform a pilot rare variant burden analysis. After extensive quality control, our cohort contained 343 CMT cases, 515 HSP cases, and 935 non-neurological controls. We assessed the cumulative mutational burden across disease genes, explored the evidence for multilocus inheritance, and performed an exome-wide rare variant burden analysis. RESULTS: We replicated the previously described mutational burden in a much larger cohort of CMT cases, and observed the same effect in HSP cases. We identified a preliminary risk allele for CMT in the EXOC4 gene (p value= 6.9 × 10-6, odds ratio [OR] = 2.1) and explored the possibility of multilocus inheritance in IA. CONCLUSION: Our results support the continuing emergence of complex inheritance mechanisms in historically Mendelian disorders.

Facile fabrication of porous BiVO4 hollow spheres with improved visible-light photocatalytic properties.

Bismuth vanadate (BiVO4) hollow spheres with porous structure have been successfully fabricated by a one-step wet solution method with no surfactant and template. The structure, morphologies, and composition of the as-prepared products were studied with X-ray powder diffraction (XRD), transmission electron morphology (TEM), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS) and UV-vis spectroscopy. Based upon the time-dependent experimental results, BiVO4 nanospheres with hollow and solid structures can be controlled effectively through the reaction time, and a reasonable formation process was suggested in this work. Moreover, the experiment of degrading methyl orange (MO) under visible-light illumination was conducted to evaluate the photocatalytic performance of the obtained BiVO4 samples. The porous BiVO4 hollow spheres exhibit superior visible-light photocatalytic properties for MO degradation than other photocatalysts under irradiation, and could be reused for up to five times without significant reduction in the photocatalytic activity. In addition, based on active group trapping experiments, ˙OH radicals as the main active species from H2O2 molecules play a vital role in the photocatalytic degradation of MO, and a photocatalytic mechanism for the BiVO4 system was proposed. High photocatalytic activity, universality and stability suggest that the porous BiVO4 hollow spheres may have potential applications in wastewater treatment.

One-pot preparation of hierarchical Cu2O hollow spheres for improved visible-light photocatalytic properties.

As visible light photocatalysts, narrow bandgap semiconductors can effectively convert solar energy to chemical energy, exhibiting potential applications in alleviating energy shortage and environmental pollution. Cu2O hollow spheres with a narrow band gap and uniform hierarchical structures have been fabricated in a controlled way. The one-pot solvothermal method without any template is simple and facile. The morphologies, crystal structures, composition, specific surface areas, and optical and photoelectric properties of the products were analyzed by various techniques. The hollow and solid Cu2O spheres could be fabricated by controlling the reaction time, and a possible growth process of the Cu2O hollow spheres was revealed. The degradation of methyl orange (MO) was used to investigate the visible-light catalytic properties of the Cu2O samples. More than 90% of MO is degraded under visible light illumination of 20 min, exhibiting a quick catalytic reaction. The rate constant of the Cu2O hollow spheres was 2.54 times and 46.6 times larger than those of the Cu2O solid spheres and commercial Cu2O powder, respectively. The possible photocatalytic mechanism of MO was revealed over Cu2O hollow spheres through the detection of active species. The as-prepared Cu2O hollow spheres display improved visible-light catalytic activity and stability, indicating their potential application in wastewater treatment.

A Rapid and Nondestructive Method for Simultaneous Determination of Aflatoxigenic Fungus and Aflatoxin Contamination on Corn Kernels.

Conventional methods for detecting aflatoxigenic fungus and aflatoxin contamination are generally time-consuming, sample-destructive, and require skilled personnel to perform, making them impossible for large-scale nondestructive screening detection, real-time, and on-site analysis. Therefore, the potential of visible-near-infrared (Vis-NIR) spectroscopy over the 400-2500 nm spectral range was examined for determination of aflatoxigenic fungus infection and the corresponding aflatoxin contamination on corn kernels in a rapid and nondestructive manner. The two A. flavus strains, AF13 and AF38, were used to represent the aflatoxigenic fungus and nonaflatoxigenic fungus, respectively, for artificial inoculation on corn kernels. The partial least-squares discriminant analysis (PLS-DA) models based on different combinations of spectral range (I: 410-1070 nm; II: 1120-2470 nm), corn side (endosperm or germ side), spectral variable number (full spectra or selected variables), modeling approach (two-step or one-step), and classification threshold (20 or 100 ppb) were developed and their performances were compared. The first study focusing on detection of aflatoxigenic fungus-infected corn kernels showed that, in classifying the "control+AF38-inoculated" and AF13-inoculated corn kernels, the full spectral PLS-DA models using the preprocessed spectra over range II and one-step approach yielded more accurate prediction results than using the spectra over range I and the two-step approach. The advantage of the full spectral PLS-DA models established using one corn side than the other side were not consistent in the explored combination cases. The best full spectral PLS-DA model obtained was obtained using the germ-side spectra over range II with the one-step approach, which achieved an overall accuracy of 91.11%. The established CARS-PLSDA models performed better than the corresponding full-spectral PLS-DA models, with the better model achieved an overall accuracy of 97.78% in separating the AF13-inoculated corn kernels and the uninfected control and AF38-inoculated corn kernels. The second study focusing on the detection of aflatoxin-contaminated corn kernels showed that, based on the aflatoxin threshold of 20 and 100 ppb, the best overall accuracy in classifying the aflatoxin-contaminated and healthy corn kernels attained 86.67% and 84.44%, respectively, using the CARS-PLSDA models. The quantitative modeling results using partial least-squares regression (PLSR) obtained the correlation coefficient of prediction set ( RP) of 0.91, which indicated the possibility of using Vis-NIR spectroscopy to quantify aflatoxin concentration in aflatoxigenic fungus-infected corn kernels.

Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a uniform 1.5-Mb duplication on chromosome 17p, which includes the PMP22 gene. Patients often present the classic neuropathy phenotype, but also with high clinical variability. OBJECTIVE: We aimed to identify genetic variants that are potentially associated with specific clinical outcomes in CMT1A. METHODS: We genotyped over 600,000 genomic markers using DNA samples from 971 CMT1A patients and performed a case-only genome-wide association study (GWAS) to identify potential genetic association in a subset of 644 individuals of European ancestry. A total of 14 clinical outcomes were analyzed in this study. RESULTS: The analyses yielded suggestive association signals in four clinical outcomes: difficulty with eating utensils (lead SNP rs4713376, chr6 : 30773314, P = 9.91×10-7, odds ratio = 3.288), hearing loss (lead SNP rs7720606, chr5 : 126551732, P = 2.08×10-7, odds ratio = 3.439), decreased ability to feel (lead SNP rs17629990, chr4 : 171224046, P = 1.63×10-7, odds ratio = 0.336), and CMT neuropathy score (lead SNP rs12137595, chr1 : 4094068, P = 1.14×10-7, beta = 3.014). CONCLUSIONS: While the results require validation in future genetic and functional studies, the detected association signals may point to novel genetic modifiers in CMT1A.