Novel Association Strategy with Copy Number Variation for Identifying New Risk Loci of Human Diseases

Copy number variations (CNV) are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP) signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases

Genome-Wide Interaction-Based Association Analysis Identified Multiple New Susceptibility Loci for Common Diseases

Genome-wide interaction-based association (GWIBA) analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS). However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named “pair-wise interaction-based association mapping” (PIAM) for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P<0.05 (P = 0.039). This interaction was replicated with a pair of proxy linked loci (P = 0.013) on an independent dataset. Five other interactions had corrected P<0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09×10−7). Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P<0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future

Forest Canopy Can Efficiently Filter Trace Metals in Deposited Precipitation in a Subalpine Spruce Plantation

Trace metals can enter natural regions with low human disturbance through atmospheric circulation; however, little information is available regarding the filtering efficiency of trace metals by forest canopies. In this study, a representative subalpine spruce plantation was selected to investigate the net throughfall fluxes of eight trace metals (Fe, Mn, Cu, Zn, Al, Pb, Cd and Cr) under a closed canopy and gap-edge canopy from August 2015 to July 2016. Over the one-year observation, the annual fluxes of Al, Zn, Fe, Mn, Cu, Cd, Cr and Pb in the deposited precipitation were 7.29 kg&#183;ha&#8722;1, 2.30 kg&#183;ha&#8722;1, 7.02 kg&#183;ha&#8722;1, 0.16 kg&#183;ha&#8722;1, 0.19 kg&#183;ha&#8722;1, 0.06 kg&#183;ha&#8722;1, 0.56 kg&#183;ha&#8722;1 and 0.24 kg&#183;ha&#8722;1, respectively. The annual net throughfall fluxes of these trace metals were &#8722;1.73 kg&#183;ha&#8722;1, &#8722;0.90 kg&#183;ha&#8722;1, &#8722;1.68 kg&#183;ha&#8722;1, 0.03 kg&#183;ha&#8722;1, &#8722;0.03 kg&#183;ha&#8722;1, &#8722;0.02 kg&#183;ha&#8722;1, &#8722;0.09 kg&#183;ha&#8722;1 and &#8722;0.08 kg&#183;ha&#8722;1, respectively, under the gap-edge canopy and 1.59 kg&#183;ha&#8722;1, &#8722;1.13 kg&#183;ha&#8722;1, &#8722;1.65 kg&#183;ha&#8722;1, 0.10 kg&#183;ha&#8722;1, &#8722;0.04 kg&#183;ha&#8722;1, &#8722;0.03 kg&#183;ha&#8722;1, &#8722;0.26 kg&#183;ha&#8722;1 and &#8722;0.15 kg&#183;ha&#8722;1, respectively, under the closed canopy. The closed canopy displayed a greater filtering effect of the trace metals from precipitation than the gap-edge canopy in this subalpine forest. In the rainy season, the net filtering ratio of trace metals ranged from &#8722;66.01% to 89.05% for the closed canopy and from &#8722;52.32% to 33.09% for the gap-edge canopy. In contrast, the net filtering ratio of all trace metals exceeded 50.00% for the closed canopy in the snowy season. The results suggest that most of the trace metals moving through the forest canopy are filtered by canopy in the subalpine forest

Gelcasting of alumina ceramics using an egg white protein binder system

Egg white protein (EW) is a food ingredient commonly used for its gelling properties and has been applied in ceramic fabrication. In this work, EW was used as an environmentally-friendly binder for gelcasting alumina ceramics at elevated temperature (80°C). The gelling behavior was compared with the ambient temperature drying-induced gelation processing. The processing conditions and mechanical properties of the ceramics processed from two different processing variants were compared. The results indicate that the ceramics from heat-induced gelation showed improved mechanical properties and more uniform microstructure after sintering in comparison to the drying-induced ones. Dense and complex-shaped ceramic parts via computer numerical controlled (CNC) green machining have been produced from the EW gelcast ceramics

Forest Gaps Inhibit Foliar Litter Pb and Cd Release in Winter and Inhibit Pb and Cd Accumulation in Growing Season in an Alpine Forest

<div><p>Aims</p><p>The release of heavy metals (such as Pb and Cd) from foliar litter play an important role in element cycling in alpine forest ecosystems. Although natural forest gaps could play important roles in the release of heavy metals from foliar litter by affecting the snow cover during the winter and solar irradiation during the growing season, few studies have examined these potential roles. The objectives of this study were to document changes in Pb and Cd dynamics during litter decomposition in the center of gaps and under closed canopies and to investigate the factors that controlled these changes during the winter and growing seasons.</p><p>Methods</p><p>Senesced foliar litter from six dominant species, including Kangding willow (<i>Salix paraplesia</i>), Masters larch (<i>Larix mastersiana</i>), Mingjiang fir (<i>Abies faxoniana</i>), Alpine azalea (<i>Rhododendron lapponicum</i>), Red birch (<i>Betula albosinensis</i>) and Mourning cypress (<i>Sabina saltuaria</i>), was placed in litterbags and incubated between the gap center and closed canopy conditions in an alpine forest in the eastern region of the Tibetan Plateau. The litterbags were sampled at the snow formation stage, snow coverage stage, snow melt stage and during the growing season. The Pb and Cd concentrations in the sampled foliar litter were determined by acid digestion (HNO₃/HClO₄).</p><p>Important findings</p><p>Over one year of decomposition, Pb accumulation and Cd release from the foliar litter occurred, regardless of the foliar litter species. However, Pb and Cd were both released from the foliar litter during the winter and accumulated during the growing season. Compared with the gap center and the canopy gap edge, the extended gap edge and the closed canopy showed higher Pb and Cd release rates in winter and higher Pb and Cd accumulation rates during the growing season, respectively. Statistical analyses indicate that the dynamics of Pb were significantly influenced by frequent freeze–thaw cycles in winter and appropriate hydrothermal conditions during the growing season, the dynamics of Cd were strongly influenced by species and the presence of a forest gap at different decomposition stages. These results show that forest gaps could inhibit Pb and Cd release from foliar litter in the alpine forest of western Sichuan. In addition, a decrease in the snow depth in the winter warming scenario would promote the release of Pb during foliar litter decomposition. There exist some difference that may be influenced by litter quality, microenvironment and microtopography during litter decomposition.</p></div

Dynamics of heavy metals in the fine sediments from a subtropical forest headwater stream during a rainy season

Headwater streams, as the capillaries of rivers, largely control the functional integrity of the entire river network. Headwater stream sediments, especially fine sediments, are essential ecosystem components and dominant reservoirs for heavy metals, with these reservoirs significantly affecting their cycling in streams. However, the dynamics of heavy metals in headwater stream sediments are not well assessed in the literature. Here, we assessed the temporal and spatial storage dynamics of several common heavy metals (i.e., Mn, Zn, Cu, Cr, Cd, and Pb) in the fine sediments from a typical subtropical forest headwater stream during the rainy season of 2021 (Mar–Aug). We found that (1) the mean storage of fine sediment of heavy metals was ordered Mn (21.57 g m−2) > Pb (2.53 g m−2) > Zn (2.27 g m−2) > Cr (0.66 g m−2) > Cu (0.12 g m−2) > Cd (0.006 g m−2); (2) their storage had a transient increase during the rainy season, followed by a decrease, but storage of both Zn and Cr was unevenly distributed from stream source to mouth; and (3) the key factors controlling heavy metal storage were water alkalinity, temperature, and pH, as well as monthly precipitation. These findings suggest that forest headwater streams can store heavy metals, but the amounts vary across temporal and spatial scales. Our results help us better understand the role of headwater streams in storing and transferring materials in forest ecosystems.</p

Summary of two-way ANOVA on the effects of gap and species on Pb and Cd release/accumulation rates at different stages (<i>n = 72</i>).

<p>Significance level:</p><p>**, <i>p</i><0.01.</p><p>SF, snow formation stage; SC, snow coverage stage; SM, snow melt stage; FT, the freeze-thaw season; GS, growing season; 1 Yr, one year.</p><p>Summary of two-way ANOVA on the effects of gap and species on Pb and Cd release/accumulation rates at different stages (<i>n = 72</i>).</p