The association between COVID-19 and cognitive performance: A Mendelian randomization analysis.

INTRODUCTION: People with COVID-19 had poorer general cognitive functioning compared to people without COVID-19. The causal link between COVID-19 and cognitive impairment is still unknown. METHODS: Mendelian randomization (MR) is a statistical approach based on genome-wide association studies (GWAS) to construct instrumental variables (IVs) and can effectively bring down the confounding bias of environmental or other disease factors, because alleles are randomly assigned to offspring. RESULTS: There was consistent evidence that cognitive performance was causally associated with COVID-19; this suggests that people with better cognitive performance are less likely to be infected with COVID-19. The reverse MR analysis treating COVID-19 as the exposure and cognitive performance as the outcome demonstrated an insignificant association, indicating the unidirectionality of the relationship. DISCUSSION: Our study provided credible evidence that cognitive performance has an impact on COVID-19. Future research should focus on long-term impact of cognitive performance on COVID-19.

Effects of Composted Agricultural Organic Materials on Mercury Methylation in Paddy Soil and Mercury Enrichment in Rice.

Many studies have shown that returning fresh straw to the field can promote mercury accumulation in crops; therefore, it is necessary to find an appropriate way to use agricultural organic materials in mercury-contaminated farmlands. In this study, pot experiments were conducted to study the effects of composted agricultural organic materials on mercury bioaccumulation in the paddy field ecosystem by adding fresh rice straw (RS), composted rice straw (CRS), cow dung (CD) and composted cow dung (CCD) to the soils. Compared with RS and CD, the CRS and CCD amendments reduced dissolved organic matter (DOM) contents in soil, but increased the aromaticity and small molecule proportion of DOM, and also increased the tartaric acid contents in soil, as well as the methylation and release of mercury in soil. However, the increased available mercury and methylmercury in the soils in the CRS and CCD treatments were not effectively absorbed by rice plants. Overall, compared with fresh organic materials, composted organic materials amendments could reduce mercury accumulation in rice to a certain extent.

Remediation of Mercury-Polluted Farmland Soils: A Review.

Mercury (Hg) bioaccumulation in Hg-polluted farmlands poses high health risk for humans and wildlife, and remediation work is urgently needed. Here, we first summarize some specific findings related to the environmental process of Hg in Hg-polluted farmlands, and distinguish the main achievements and deficiencies of available remediation strategies in recent studies. Results demonstrate that farmland is a sensitive area with vibrant Hg biogeochemistry. Current remediation methods are relatively hysteretic whether in mechanism understanding or field application, and deficient for large-scale Hg-polluted farmlands in view of safety, efficiency, sustainability, and cost-effectiveness. New perspectives including environment-friendly functional materials, assisted phytoremediation and agronomic regulations are worthy of further study as their key roles in reducing Hg exposure risk and protecting agricultural sustainability.

Effects of fulvic acid and humic acid from different sources on Hg methylation in soil and accumulation in rice.

Humus is often used as an organic modifier to reduce the bioaccumulation of heavy metals in plants, but the effects of different humus components from different sources on the fate of mercury (Hg) in paddy fields are still unclear. Here, fulvic acid (FA) and humic acid (HA) extracted from composted straw (CS), composted cow dung (CCD), peat soil (PM) and lignite coal (LC) were used to understand their effects on the methylation and bioaccumulation of Hg in paddy soil by pot experiments. Amendments of both FA and HA largely increased the abundance of Hg-methylating microbes and low-molecular-weight organic matters (e.g, cysteine) in paddy soil. They were also found to change the aromaticity, molecular size and Chromophoric DOM concentration of DOM, and resulted in heterogeneous effects on migration and transformation of Hg. All the FA-amended treatments increased the mobility and methylation of Hg in soil and its absorption in roots. Nevertheless, FA from different sources have heterogeneous effects on transport of Hg between rice tissues. FA-CCD and FA-PM promoted the translocation of MeHg from roots to rice grains by 32.95% and 41.12%, while FA-CS and FA-LC significantly inhibited the translocation of inorganic Hg (IHg) by 52.65% and 66.06% and of MeHg by 46.65% and 36.23%, respectively. In contrast, all HA-amended treatments reduced the mobility of soil Hg, but promoted Hg methylation in soil. Among which, HA-CCD and HA-PM promoted the translocation of MeHg in rice tissues by 88.95% and 64.10%, while its accumulation in rice grains by 28.43% and 28.69%, respectively. In general, the application of some FA and HA as organic modifiers to reduce Hg bioaccumulation in rice is not feasible.

Three pleiotropic loci associated with bone mineral density and lean body mass.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10-8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10-8, replication p = 1.03 × 10-4), 16q12.2 (rs1421085, discovery p = 2.04 × 10-9, replication p = 6.47 × 10-14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10-8, replication p = 6.69 × 10-6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

Mercury Bioaccumulation in Freshwater Snails as Influenced by Soil Composition.

Soil properties largely control the fate of mercury (Hg), including the synthesis of neurovirulent methylmercury (MeHg). Here, the freshwater snail (Cipangopaludina cahayensis), a snail species commonly bred in flooded farmland, was used in a test of biotoxicity exposure to explore the effects of soil components on Hg bioavailability. The results show that snails incubated on the surface of slightly Hg-polluted flooded soil (2.0 mg/kg) have MeHg concentrations of 7.9 ± 1.5 mg/kg, which greatly exceed the limit of contaminants in food in China (0.5 mg/kg). The addition of ferrous disulfide can significantly increase the MeHg concentrations in soils while reducing the concentrations of total Hg (THg) and MeHg levels in snails by 59.1% and 64.3%, respectively. Peat-derived fulvic acid has the capacity to reduce the MeHg concentrations in soils and snails by 23.8% and 33.2%, respectively, whereas it increases the dissolved Hg levels in overlying water by 104.3%. Moreover, Fe-Mn oxides and humic acid can consistently reduce THg and MeHg concentrations in snails. Overall, freshwater snails bred in Hg-polluted areas may suffer from a high risk of Hg exposure, and importantly, some soil components such as ferrous disulfide and humic acid have strong inhibitory effects on Hg bioaccumulation in snails.

Four pleiotropic loci associated with fat mass and lean mass.

BACKGROUND: Fat mass and lean mass are two biggest components of body mass. Both fat mass and lean mass are under strong genetic determinants and are correlated. METHODS: We performed a bivariate genome-wide association meta-analysis of (lean adjusted) leg fat mass and (fat adjusted) leg lean mass in 12,517 subjects from 6 samples, and followed by in silico replication in large-scale UK biobank cohort sample (N = 370 097). RESULTS: We identified four loci that were significant at the genome-wide significance (GWS, α = 5.0 × 10-8) level at the discovery meta-analysis, and successfully replicated in the replication sample: 2q36.3 (rs1024137, pdiscovery = 3.32 × 10-8, preplication = 4.07 × 10-13), 5q13.1 (rs4976033, pdiscovery = 1.93 × 10-9, preplication = 6.35 × 10-7), 12q24.31 (rs4765528, pdiscovery = 7.19 × 10-12, preplication = 1.88 × 10-11) and 18q21.32 (rs371326986, pdiscovery = 9.04 × 10-9, preplication = 2.35 × 10-95). The above four pleiotropic loci may play a pleiotropic role for fat mass and lean mass development. CONCLUSIONS: Our findings further enhance the understanding of the genetic association between fat mass and lean mass and provide a new theoretical basis for their understanding.

Identification of a 1p21 independent functional variant for abdominal obesity.

OBJECTIVES: Aiming to uncover the genetic basis of abdominal obesity, we performed a genome-wide association study (GWAS) meta-analysis of trunk fat mass adjusted by trunk lean mass (TFMadj) and followed by a series of functional investigations. SUBJECTS: A total of 11,569 subjects from six samples were included into the GWAS meta-analysis. METHODS: Meta-analysis was performed by a weighted fixed-effects model. In silico replication analysis was performed in the UK-Biobank (UKB) sample (N = 331,093) and in the GIANT study (N up to 110,204). Cis-expression QTL (cis-eQTL) analysis, dual-luciferase reporter assay and electrophoresis mobility shift assay (EMSA) were conducted to examine the functional relevance of the identified SNPs. At last, differential gene expression analysis (DGEA) was performed. RESULTS: We identified an independent SNP rs12409479 at 1p21 (MAF = 0.07, p = 7.26 × 10-10), whose association was replicated by the analysis of TFM in the UKB sample (one-sided p = 3.39 × 10-3), and was cross-validated by the analyses of BMI (one-sided p = 0.03) and WHRadj (one-sided p = 0.04) in the GIANT study. Cis-eQTL analysis demonstrated that allele A at rs12409479 was positively associated with PTBP2 expression level in subcutaneous adipose tissue (N = 385, p = 4.15 × 10-3). Dual-luciferase reporter assay showed that the region repressed PTBP2 gene expression by downregulating PTBP2 promoter activity (p < 0.001), and allele A at rs12409479 induced higher luciferase activity than allele G did (p = 4.15 × 10-3). EMSA experiment implied that allele A was more capable of binding to unknown transcription factors than allele G. Lastly, DGEA showed that the level of PTBP2 expression was higher in individuals with obesity than in individuals without obesity (N = 20 and 11, p = 0.04 and 9.22 × 10-3), suggesting a regulatory role in obesity development. CONCLUSIONS: Taken together, we hypothesize a regulating path from rs12409479 to trunk fat mass development through its allelic specific regulation of PTBP2 gene expression, thus providing some novel insight into the genetic basis of abdominal obesity.

Meta-analysis of genome-wide association data identifies novel susceptibility loci for obesity.

Obesity is a major public health problem with strong genetic determination. Multiple genetic variants have been implicated for obesity by conducting genome-wide association (GWA) studies, primarily focused on body mass index (BMI). Fat body mass (FBM) is phenotypically more homogeneous than BMI and is more appropriate for obesity research; however, relatively few studies have been conducted on FBM. Aiming to identify variants associated with obesity, we carried out meta-analyses of seven GWA studies for BMI-related traits including FBM, and followed these analyses by de novo replication. The discovery cohorts consisted of 21 969 individuals from diverse ethnic populations and a total of over 4 million genotyped or imputed SNPs. The de novo replication cohorts consisted of 6663 subjects from two independent samples. To complement individual SNP-based association analyses, we also carried out gene-based GWA analyses in which all variations within a gene were considered jointly. Individual SNP-based association analyses identified a novel locus 1q21 [rs2230061, CTSS (Cathepsin S)] that was associated with FBM after the adjustment of lean body mass (LBM) (P = 3.57 × 10(-8)) at the genome-wide significance level. Gene-based association analyses identified a novel gene NLK (nemo-like kinase) in 17q11 that was significantly associated with FBM adjusted by LBM. In addition, we confirmed three previously reported obesity susceptibility loci: 16q12 [rs62033400, P = 1.97 × 10(-14), FTO (fat mass and obesity associated)], 18q22 [rs6567160, P = 8.09 × 10(-19), MC4R (melanocortin 4 receptor)] and 2p25 [rs939583, P = 1.07 × 10(-7), TMEM18 (transmembrane protein 18)]. We also found that rs6567160 may exert pleiotropic effects to both FBM and LBM. Our results provide additional insights into the molecular genetic basis of obesity and may provide future targets for effective prevention and therapeutic intervention.

Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

A new method for estimating effect size distribution and heritability from genome-wide association summary results.

Accurately estimating the distribution and heritability of SNP effects across the genome could help explain the mystery of missing heritability. In this study, we propose a novel statistical method for estimating the distribution and heritability of SNP effects from genome-wide association studies (GWASs), and compare its performance to several existing methods using both simulations and real data. Specifically, we study the full range of GWAS summary results and link observed p values and unobserved effect sizes by (non-central) Chi-square distribution. By modeling the observed full set of association signals using a multinomial distribution, we build a likelihood function of SNP effect sizes using parametric and non-parametric maximum likelihood frameworks. Simulation studies show that the proposed method can accurately estimate effect sizes and the number of associated SNPs. As real applications, we analyze publicly available GWAS summary results for height, body mass index (BMI), and bone mineral density (BMD). Our analyses show that there are over 10,000 SNPs that might be associated with height, and the total heritability attributable to these SNPs exceeds 70 %. The heritabilities for BMI and BMD are ~10 and ~15 %, respectively. The results indicate that the proposed method has the potential to improve the accuracy of estimates of heritability and effect size for common SNPs in large-scale GWAS meta-analyses. These improved estimates may contribute to an enhanced understanding of the genetic basis of complex traits.

Identification of LRRK2 gene related to sarcopenia and neuroticism using weighted gene co-expression network analysis.

BACKGROUND: Sarcopenia is reported to be associated with neuroticism, but the mechanisms are not fully understood. Thus, it's of vital importance to elucidate the molecular mechanism of sarcopenia and neuroticism and to explore the potential molecular target of medical therapies for sarcopenia and neuroticism. METHODS: The expression datasets (sarcopenia: GSE111006 and neuroticism: GSE60491) were downloaded from the Gene Expression Omnibus. Weighted gene co-expression network analysis (WGCNA) was used to build the gene co-expression network, screen important modules, and filter the hub genes. Genes with significance over 0.2 and a module membership over 0.8 were hub genes. The overlapped hub genes between sarcopenia and neuroticism were defined as key genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the genes in modules with clinical interest. RESULTS: In this study, we identified 28 gene modules for sarcopenia and 7 for neuroticism by WGCNA. The key modules of sarcopenia and neuroticism were the tan and turquoise modules, respectively. Hub genes of sarcopenia and neuroticism were 20 genes and 107 genes, respectively. The function enrichment found that apoptosis was the common pathway for sarcopenia and neuroticism. Finally, LRRK2 was identified as key genes. LIMITATIONS: The sarcopenia dataset contained fewer samples. CONCLUSION: Based on WGCNA, our study identified apoptosis pathway and LRRK2 that acted as essential components in the etiology of sarcopenia and neuroticism, which may enhance our fundamental knowledge of the molecular mechanisms underlying the disease.

The Effects of Different Soil Component Couplings on the Methylation and Bioavailability of Mercury in Soil.

Soil composition can influence the chemical forms and bioavailability of soil mercury (Hg). However, previous studies have predominantly focused on the influence of individual components on the biogeochemical behavior of soil Hg, while the influence of various component interactions among several individual factors remain unclear. In this study, artificial soil was prepared by precisely regulating its components, and a controlled potted experiment was conducted to investigate the influence of various organic and inorganic constituents, as well as different soil textures resulting from their coupling, on soil Hg methylation and its bioavailability. Our findings show that inorganic components in the soils primarily exhibit adsorption and fixation effects on Hg, thereby reducing the accumulation of total mercury (THg) and methylmercury (MeHg) in plants. It is noteworthy that iron sulfide simultaneously resulted in an increase in soil MeHg concentration (277%). Concentrations of THg and MeHg in soil with peat were lower in rice but greater in spinach. A correlation analysis indicated that the size of soil particles was a crucial factor affecting the accumulation of Hg in plants. Consequently, even though fulvic acid activated soil Hg, it significantly increased the proportion of soil particles smaller than 100.8 µm, thus inhibiting the accumulation of Hg in plants, particularly reducing the concentration of THg (93%) and MeHg (85%) in water spinach. These results demonstrate that the interaction of organic and inorganic components can influence the biogeochemical behavior of soil Hg not only through their chemical properties, but also by altering the soil texture.

Mercury and methylmercury in Hg-contaminated paddy soil and their uptake in rice as regulated by DOM from different agricultural sources.

In this study, from the perspectives of structural and compositional variations of soil-dissolved organic matter (DOM), we explored the effects of agricultural DOM inputs on methylmercury (MeHg) accumulation in the soil and mercury (Hg) bioaccumulation in rice grains. Pot experiments with the addition of DOMs from maize straw (MaS), rape straw (RaS), rice straw (RiS), composted rice straw (CRiS), cow dung (CD), and composted cow dung (CCD) were then conducted. Results showed that, relative to the control, the DOM amendment from each agricultural source elevated MeHg concentrations in the soil, with an increase of 18-227%, but only parts of DOMs elevated total dissolved Hg (DHg) and MeHg (DMeHg) concentrations in pore water. Among all DOM species, RiS, CRiS, and CCD significantly increased total Hg (THg) and MeHg contents in rice grains by 34-64% and 32-118%, respectively. Compared with RiS, THg and MeHg contents in rice grains in the CRiS treatment decreased slightly, which was consistent with the distributions of DHg and DMeHg concentrations in pore water and the aromaticity variation of soil DOM. In contrast, the CCD input significantly enhanced the enrichment of THg and MeHg in rice grains relative to CD because it significantly reduced the humification of soil DOM at all rice-growing stages while increasing the low-molecular-weight fractions in soil DOM. The THg and MeHg contents in the rice grains were significantly lower treated by RaS than those by MaS and RiS, which may be related to the higher sulfur-containing compounds such as sulfate and cysteine in rape straw or its DOM solution. Overall, DOM amendment from different agricultural sources resulted in significantly discriminative effects on the MeHg accumulation in soil and Hg enrichment in rice in the Hg-contaminated paddy field by shaping soil DOM properties.