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Weihua Zhang

Publications and source records attributed to Weihua Zhang.

At least 19 recordsLinked to original sources
PubMed2025

Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.

Female↗
PubMed2007

Diagnosis of gastric cancer using decision tree classification of mass spectral data.

Although gastric cancer is the second leading cause of cancer death worldwide, specific and sensitive biomarkers that can be used for its diagnosis are still unavailable. Attempting to improve on current approaches to the serological diagnosis of gastric cancer, we subjected serum samples from 245 individuals (including 127 gastric cancer patients, 100 age- and sex-matched healthy individuals, nine benign gastric lesion patients and nine colorectal cancer patients) for analysis by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. Peaks were detected with Ciphergen SELDI software version 3.1.1 and analyzed with Biomarker Patterns' software 5.0. We developed a classifier for separating the gastric cancer groups from the healthy groups. Three protein masses with 1468, 3935 and 7560 m/z were selected as a potential 'fingerprint' for the detection of gastric cancer. It was able to distinguish the gastric cancer patients from the health volunteers with a sensitivity of 95.6% and a specificity of 92.0% in the training set. In the blinding set, it was capable of differentiating the gastric cancer samples from the others with a specificity of 88.0%, a sensitivity of 85.3%, and an accuracy of 86.4%. These values were all higher than those achieved in a parallel analysis by measuring serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 together. Therefore, the decision tree analysis of serum proteomic patterns has the potential to be used in gastric cancer diagnosis.

Adolescent↗
PubMed2006

Genome scanning by composite likelihood.

Ambitious programs have recently been advocated or launched to create genomewide databases for meta-analysis of association between DNA markers and phenotypes of medical and/or social concern. A necessary but not sufficient condition for success in association mapping is that the data give accurate estimates of both genomic location and its standard error, which are provided for multifactorial phenotypes by composite likelihood. That class includes the Malecot model, which we here apply with an illustrative example. This preliminary analysis leads to five inferences: permutation of cases and controls provides a test of association free of autocorrelation; two hypotheses give similar estimates, but one is consistently more accurate; estimation of the false-discovery rate is extended to causal genes in a small proportion of regions; the minimal data for successful meta-analysis are inferred; and power is robust for all genomic factors except minor-allele frequency. An extension to meta-analysis is proposed. Other approaches to genome scanning and meta-analysis should, if possible, be similarly extended so that their operating characteristics can be compared.

Chromosome Mapping↗
PubMed2006

Removal of Pb and MDF from contaminated soils by EDTA- and SDS-enhanced washing.

Heavy metal- and organic-contaminated sites are ubiquitous, but few studies have been conducted to address such an issue. EDTA- and SDS-enhanced washing was studied for remediation of Pb- and/or marine diesel fuel (MDF)-contaminated soils. The feasibility of recovery and reuse of EDTA and SDS, as well as the physicochemical interactions among the chemical agents, contaminants and soils were extensively investigated using batch experiments. The optimal washing sequence was then determined. The experimental results showed that EDTA could be recovered and reused for four cycles without significant loss of its chelating capacity, while the extraction capability of SDS was noticeably reduced after each reuse cycle. The free phase of marine diesel fuel (MDF) in soils physically isolated the sorbed Pb on soils and thus reducing its extraction by EDTA. The presence of SDS alone or together with low concentration of EDTA was found to enhance Pb removal probably via electrostatic interaction and dissolution of soil organic matter. However, it hindered Pb extraction by high concentration of EDTA, because of the potential formation of complexes between some strongly-bound Pb and SDS, that are more resistant to desorption. Therefore, EDTA washing followed by SDS achieved the highest Pb removal efficiency. On the other hand, MDF removal by SDS was significantly hindered by coexisting Pb in soils, probably because the formation of Pb-dodecyl sulfate (DS) complex would decrease the effective amount of SDS available for forming micelles in solution and enhance MDF sorption. EDTA alone or together with SDS could enhance MDF removal, but the residual MDF after EDTA-washing became more resistant to SDS removal. Consequently, SDS washing followed by EDTA is considered as the optimal washing sequence for MDF removal.

Chromatography, High Pressure Liquid↗
PubMed2006

Rapid and complete dechlorination of PCP in aqueous solution using Ni-Fe nanoparticles under assistance of ultrasound.

The Ni-Fe bimetallic particles have been laboratory prepared using sodium borohydride (NaBH4) as the reductant to reduce Ni2+ and Fe2+ in aqueous solution simultaneously, and characterized by TEM, XRD, BET and XPS. The particles were proved to be nanoscale amorphous alloy with an average diameter of about 30 nm and a BET surface area of 20.9 m2 g(-1). Experiments for dechlorination of pentachlorophenol (PCP) by the Ni-Fe bimetallic nanoscale particles in aqueous solutions were carried out under the enhancement of ultrasound. Major factors that influence the dechlorination efficiency, such as initial pH value, Ni content in the Ni-Fe particles, and output power of ultrasonic irradiation, were investigated. The results indicated that Ni-Fe nanoscale bimetallic particles were very effective for the dechlorination of PCP. Dechlorination efficiency was 46% in 30 min under the optimal condition without assistance of ultrasound, whereas it increased to 96% when ultrasonic irradiation was present. Initial pH value showed apparent effect on the dechlorination. As the pH varied from acidic condition to neutral condition, the dechlorination efficiency decreased dramatically. In addition, the dechlorination efficiency was improved with increased Ni/Fe ratio and ultrasonic output power. Less chlorinated phenols including tetrachlorophenol, trichlorophenol, dichlorophenol, monochlorophenol were formed during the initial reaction, and phenol was determined by GC-MS as sole product in the end of reaction.

Environmental Pollutants↗
PubMed2006

Investigation of disulfonamide ligands derived from o-phenylenediamine and their Pb(II) complexes by electrospray ionization mass spectrometry.

An electrospray ionization mass spectrometry (ESI-MS) method, in both positive and negative ion modes, was developed for characterization of disulfonamide ligands derived from o-phenylenediamine and their Pb(II) complexes. For the ligands, negative ion mode ESI-MS in methanolic solutions gave simple and easily interpretable mass spectra. However, the spectra of Pb complexes were not readily interpretable under the same conditions. Protonated ligands and their Pb(II) complexes were observed in methanolic solutions by ESI-MS in positive ion mode. The formation of Na(+), K(+), or NH(4) (+) adducts was also observed, complicating the mass spectra and decreasing the signal intensity. In order to optimize the detection of the ligands and the Pb complexes, a method was developed by adding NaOAc in the solutions. The presence of 0.2 mM NaOAc simplified the mass spectra of the ligands and the Pb complexes, and significantly increased sensitivity in both negative and positive ion modes. This modification makes ESI-MS in both modes suitable for characterization of sulfonamide ligands and their Pb complexes, thus providing a potentially powerful tool for evaluating formation of metal complexes and screening combinatorial ligand libraries.

Lead↗
PubMed2006

Enhancement of Raman signals with silver-coated tips.

Silver coated SiN and SiO(2) tips have been fabricated for use with a bottom-illumination tip-enhanced Raman spectroscopy (TERS) setup with a 488 nm laser excitation. SiN tips with 50-60 nm of deposited Ag give the best TERS enhancements for brilliant cresyl blue test analyte spin-coated on a glass slide. Ag nanoparticles on SiN or SiO(2) rather than Si tips are better for TERS because of the proximity of the wavelengths of their surface plasmon resonance to 488 nm. Adjustments of tilt angle of the metallized tip with respect to the surface plane is shown to considerably raise the intensities of the TERS signals, even from tips that initially appear to be rather non-enhancing. This work helps to enable the more frequent use of the 488 nm laser for nanoscale chemical analysis with both TERS and fluorescence imaging in the same setup.

Microscopy, Scanning Probe↗
PubMed2006

Loss of adhesion in the circulation converts amelanotic metastatic melanoma cells to melanotic by inhibition of AKT.

Direct injection of murine K-1735 melanoma cells into the subcutis, lung, or brain of syngeneic mice produces amelanotic tumors, whereas intravenous injection into the lateral tail vein or internal carotid artery produces both amelanotic and melanotic foci in the lung and the brain respectively. We hypothesized that loss of adhesion in the circulation may contribute to the melanogenic phenotypes of cells. To test this, we used enforced suspension culture of K-1735 cells by consistent rotating culture of K-1735 cells. We found that the expression of the microphthalmia transcription factor (MITF) and melanin-stimulating hormone receptor (MSHR) were upregulated in cells growing in suspension and were accompanied by inhibitions of AKT and ERK, which were reversed in cells upon regrowth as an adherent monolayer. Inhibition of the AKT pathway was responsible for MITF induction by suspension culture. Stable expression of constitutively active AKT significantly repressed the melanogenesis of K-1735 cells injected via circulation. An amelanotic clone of K-1735 cells was resistant to suspension culture-induced MITF, although the inhibition of AKT pathway was intact. Collectively, these data suggest that the inhibition of AKT pathway due to loss of adhesion within the circulation renders a subpopulation of K-1735 cells to produce melanin.

Animals↗
PubMed2005

Cosmopolitan linkage disequilibrium maps.

Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD) and maps of single nucleotide polymorphisms (SNPs), it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection), the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

Chromosome Mapping↗
PubMed2004

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences.

Alleles↗
PubMed2004

Arsenic complexes in the arsenic hyperaccumulator Pteris vittata (Chinese brake fern).

Pteris vittata (Chinese brake fern), the first reported arsenic (As) hyperaccumulating plant, can be potentially applied in the phytoremediation As-contaminated sites. Understanding the mechanisms of As tolerance and detoxification in this plant is critical to further enhance its capability of As hyperaccumulation. In this study, an unknown As species, other than arsenite (AsIII) or arsenate (AsV) was found in leaflets by using anion-exchange chromatography-hydride generation-atomic fluorescence spectroscopy and size-exclusion chromatography-atomic fluorescence spectrometry. The chromatographic behavior of this unknown As species and its stability suggest that it is likely an As complex. Although phytochelatin with two subunits (PC2) was the only major thiol in P. vittata under As exposure, this unknown As complex was unlikely to be an AsIII-PC2 complex by comparison of their chromatographic behaviors, stability at different pHs and charge states. The complex is sensitive to temperature and metal ions, but relatively insensitive to pH. In buffer solution of pH 5.9, it is present in a neutral form.

Arsenicals↗
PubMed2004

Does haplotype diversity predict power for association mapping of disease susceptibility?

Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of "haplotype-tagging" single-nucleotide polymorphisms (SNPs) that identify the most common haplotypes. These studies are motivated by the assumption that retention of haplotype diversity assures retention of power for mapping disease susceptibility by allelic association. Using two bodies of real data, three proposed measures of diversity, and regression-based methods for association mapping, we found no scenario for which this assumption was tenable. We compared the chi-square for composite likelihood and the maximum chi-square for single SNPs in diplotypes, excluding the marker designated as causal. All haplotype-tagging methods conserve haplotype diversity by selecting common SNPs. When the causal marker has a range of allele frequencies as in real data, chi-square decreases faster than under random selection as the haplotype-tagging set diminishes. Selecting SNPs by maximizing haplotype diversity is inefficient when their frequency is much different from the unknown frequency of the causal variant. Loss of power is minimized when the difference between minor allele frequencies of the causal SNP and a closely associated marker SNP is small, which is unlikely in ignorance of the frequency of the causal SNP unless dense markers are used. Therefore retention of haplotype diversity in simulations that do not mirror genomic allele frequencies has no relevance to power for association mapping. TagSNPs that are assigned to bins instead of haplotype blocks also lose power compared with random SNPs. This evidence favours a multi-stage design in which both models and density change adaptively.

Gene Frequency↗
PubMed2004

Positional cloning by linkage disequilibrium.

Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for positional cloning by LD within a composite likelihood framework and investigate the operating characteristics of maps in physical units (kb) and LDU for two bodies of data (Daly et al. 2001; Jeffreys et al. 2001) on which current ideas of blocks are based. False-negative indications of a disease locus (type II error) were examined by selecting one single-nucleotide polymorphism (SNP) at a time as causal and taking its allelic count (0, 1, or 2, for the three genotypes) as a pseudophenotype, Y. By use of regression and correlation, association between every pseudophenotype and the allelic count of each SNP locus (X) was based on an adaptation of the Malecot model, which includes a parameter for location of the putative gene. By expressing locations in kb or LDU, greater power for localization was observed when the LDU map was fitted. The efficiency of the kb map, relative to the LDU map, to describe LD varied from a maximum of 0.87 to a minimum of 0.36, with a mean of 0.62. False-positive indications of a disease locus (type I error) were examined by simulating an unlinked causal SNP and the allele count was used as a pseudophenotype. The type I error was in good agreement with Wald's likelihood theorem for both metrics and all models that were tested. Unlike tests that select only the most significant marker, haplotype, or haploset, these methods are robust to large numbers of markers in a candidate region. Contrary to predictions from tagging SNPs that retain haplotype diversity, the sample with smaller size but greater SNP density gave less error. The locations of causal SNPs were estimated with the same precision in blocks and steps, suggesting that block definition may be less useful than anticipated for mapping a causal SNP. These results provide a guide to efficient positional cloning by SNPs and a benchmark against which the power of positional cloning by haplotype-based alternatives may be measured.

Alleles↗
PubMed2004

Thiol synthesis and arsenic hyperaccumulation in Pteris vittata (Chinese brake fern).

Pteris vittata (Chinese brake fern) has potential for phytoremediation of As-contaminated sites. In this study, the synthesis of total thiols and acid-soluble thiols in P. vittata was investigated under arsenic exposure. The strong and positive correlation between As concentration and acid-soluble thiols in plant leaflets suggests that acid-soluble thiols may play a role in As detoxification. A major As-induced thiol was purified and characterized. A molecular ion (M + 1) of 540 m/z suggests that the thiol was a phytochelatin (PC) with two base units (PC(2)). However, the ratios of acid-soluble thiols to As in leaflets exposed to As ranged from 0.012 to 0.026, suggesting that only a very small part of As is complexed by PC(2). PCs could play a minor detoxification role in this hyperaccumulator. A PC-independent mechanism appears to be mainly involved in As tolerance, while PC-dependent detoxification seems to be a supplement.

Arsenic↗
PubMed2003

Purification and characterization of thiols in an arsenic hyperaccumulator under arsenic exposure.

Pteris vittata (Chinese brake fern) is the first reported arsenic hyperaccumulator. To investigate the arsenic tolerance mechanism in this plant, reversed-phase HPLC with postcolumn derivatization was used to analyze the thiols induced under arsenic exposure. A major thiol in the plant leaflets was found to be responsive to arsenic exposure. The arsenic-induced compound was purified on a large scale by combining covalent chromatography and preparative reversed-phase HPLC. About 2 mg of this compound was isolated from 1 kg of fresh leaflets. The purified arsenic-induced compound was characterized using electrospray ionization mass spectrometry. A molecular ion (M + 1) of 540 and fragments were obtained, which indicated that the arsenic-induced thiol was a phytochelatin with two subunits (PC(2)). Compared to the classical methods for purification of phytochelatins, this new method is more specific, simple, and rapid and is suitable for purification of PCs in a large scale as well as sample preparation for mass spectrometry analysis.

Journal Article↗
PubMed2003

Linkage disequilibrium in human populations.

Whereas the human linkage map appears on limited evidence to be constant over populations, maps of linkage disequilibrium (LD) vary among populations that differ in gene history. The greatest difference is between populations of sub-Saharan origin and populations remotely derived from Africa after a major bottleneck that reduced their heterozygosity and altered their Malecot parameters, increasing the intercept M that reflects association in founders and decreasing the exponential decline epsilon. Variation among populations within this ethnic dichotomy is much smaller. These observations validate use of a cosmopolitan LD map based on a sizeable sample representing a large population reliably typed for markers at high density. Then an LD map for a region or isolate within an ethnic group may be created by fitting the sample LD to the cosmopolitan map, estimating Malecot parameters simultaneously. The cosmopolitan map scaled by epsilon recovers 95% of the information that a local map at the same density gives and therefore more than the information in a low-resolution local map. Relative to a Eurasian cosmopolitan map the scaling factors are estimated to be 0.82 for isolates of European descent, 1.53 for Yorubans, and 1.74 for African Americans. These observations are consistent with a common bottleneck (perhaps but not necessarily speciation) approximately 173,500 years ago, if the bottleneck associated with migration out of Africa was 100,000 years ago. Eurasian populations (especially isolates with numerous cases) are efficient for genome scans, and populations of recent African origin (such as African Americans) are efficient for identification of causal polymorphisms within a candidate sequence.

Chromosome Mapping↗