Biomedical subjects

Lang Wu

Publications and source records attributed to Lang Wu.

8 recordsLinked to original sources

PubMed2025

Proteome-wide association study of prostate cancer risk across populations.

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls of European population, 10,809 cases and 95,790 controls of Asian population, and 3931 cases and 26,405 controls of Hispanic/Latino population. We identify three, four, 15, and 73 PCa-associated proteins in African, Hispanic/Latino, Asian, and European populations, respectively, and 83 in trans-population meta-analysis. There are both pan-population and population-specific associations. Our findings provide valuable insights into etiology of PCa.

Humans↗

PubMed2025

Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse normalization by study and half-minimum imputation provide mostly similar results for pooled or meta-analysis. Following the practical analysis framework, we further performed a genome-wide association analysis on 1,135 selected metabolites using whole-genome sequencing data from 16,359 individuals passing the quality-control filters and discovered 1,775 independent loci associated with 667 metabolites. Among 160 unreported locus-metabolite pairs, we identified associations with loci locating within previously implicated metabolite-associated genes, as well as associations with loci locating in genes such as GAB3 and VSIG4 (located on the X chromosome) that may play a role in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, which were located in well-known metabolic genes such as FADS2, D2HGDH, SUGP1, and UGT2B17, strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.

Humans↗

PubMed2025

Slmsh1-induced heritable enhancement of traits for tomato breeding improvement.

Vegetable grafting is a horticultural technique employed to develop specialized plant varieties by effectively enhancing resistance to both biotic and abiotic stresses, as well as improving fruit quality and yield. However, these advantageous traits are generally non-heritable. The MSH1 gene induced heritable enhancement-through-grafting (HEG) effect on growth vigor, demonstrating promising application potential. In this study, we employed the msh1 mutant tomato as a rootstock to induce heritable superior traits and combined this approach with hybridization techniques to enhance tomato cultivars. Three Slmsh1 mutants were generated using CRISPR/Cas9 which exhibited a dwarf phenotype with whitened spots. By grafting several distinct inbred lines onto Slmsh1, we observed significant HEG, drought stress tolerance, and fruit quality. Under drought conditions, Slmsh1-grafted tomato seedlings exhibited increased biomass and enhanced drought tolerance through the regulation of antioxidant enzyme activities. Differential expression and methylation analyses of the graft progeny revealed that these heritable enhanced traits (HETs) are likely attributable to epigenetic modifications in the expression of ROS-scavenging- and hormone-related genes. Furthermore, to explore practical applications, we crossed inbred lines with HETs and evaluated the growth, yield, and fruit quality of the resulting hybrid combinations. The results indicated that these hybrid combinations improved fruit yield and quality, enhancing the total soluble solids, soluble sugar, and soluble protein content. These findings suggest that Slmsh1-grafted progenies enhanced plant biomass and drought resistance, while their hybrid combinations positively influenced root growth, yield, and fruit quality, providing new insights into the synergistic integration of genome editing and conventional breeding.

Solanum lycopersicum↗

PubMed2004

Simultaneous inference for longitudinal data with detection limits and covariates measured with errors, with application to AIDS studies.

In AIDS studies such as HIV viral dynamics, statistical inference is often complicated because the viral load measurements may be subject to left censoring due to a detection limit and time-varying covariates such as CD4 counts may be measured with substantial errors. Mixed-effects models are often used to model the response and the covariate processes in these studies. We propose a unified approach which addresses the censoring and measurement errors simultaneously. We estimate the model parameters by a Monte-Carlo EM algorithm via the Gibbs sampler. A simulation study is conducted to compare the proposed method with the usual two-step method and a naive method. We find that the proposed method produces approximately unbiased estimates with more reliable standard errors. A real data set from an AIDS study is analysed using the proposed method.

Acquired Immunodeficiency Syndrome↗

PubMed2004

A note on one-sided tests with multiple endpoints.

Testing problems with multivariate one-sided alternative hypotheses are common in clinical trials with multiple endpoints. In the case of comparing two treatments, treatment 1 is often preferred if it is superior for at least one of the endpoints and not biologically inferior for the remaining endpoints. Bloch et al. (2001, Biometrics57, 1039-1047) propose an intersection-union test (IUT) for this testing problem, but their test does not utilize the appropriate multivariate one-sided test. In this note we modify their test by an alternative IUT that does utilize the appropriate one-sided test. Empirical and graphical evidence show that the proposed test is more appropriate for this testing problem.

Biometry↗

PubMed2003

Bereaved parents' outcomes 4 to 60 months after their children's deaths by accident, suicide, or homicide: a comparative study demonstrating differences.

In this article, the authors revisit a controversial issue in the bereavement field: Does one violent cause of death of a child influence parents' outcomes more than another? To address this question, we observed 173 parents prospectively 4, 12, 24, and 60 months after their children's deaths by accident, suicide, or homicide. Quantitative and qualitative research methods were used to examine the influence of three types of a child's violent death and time since death upon 4 parent outcomes (mental distress, post-traumatic stress disorder [PTSD], acceptance of the child's death, and marital satisfaction). The results showed a significant interaction for the bereavement Group x Time effect for acceptance of death, a significant main effect for time for all four outcomes, and a significant main effect for group (homicide) for PTSD. Nearly 70% of the parents reported that it took either 3 or 4 years to put their children's death into perspective and continue with their own lives; however the child's cause of death did not significantly influence parents' sense of timing in this regard. Clinical and research implications of the findings are discussed.

Accidents↗

PubMed2002

Identification of significant host factors for HIV dynamics modelled by non-linear mixed-effects models.

Non-linear mixed-effects models are powerful tools for modelling HIV viral dynamics. In AIDS clinical trials, the viral load measurements for each subject are often sparse. In such cases, linearization procedures are usually used for inferences. Under such linearization procedures, however, standard covariate selection methods based on the approximate likelihood, such as the likelihood ratio test, may not be reliable. In order to identify significant host factors for HIV dynamics, in this paper we consider two alternative approaches for covariate selection: one is based on individual non-linear least square estimates and the other is based on individual empirical Bayes estimates. Our simulation study shows that, if the within-individual data are sparse and the between-individual variation is large, the two alternative covariate selection methods are more reliable than the likelihood ratio test, and the more powerful method based on individual empirical Bayes estimates is especially preferable. We also consider the missing data in covariates. The commonly used missing data methods may lead to misleading results. We recommend a multiple imputation method to handle missing covariates. A real data set from an AIDS clinical trial is analysed based on various covariate selection methods and missing data methods.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Flexible weighted log-rank tests optimal for detecting early and/or late survival differences.

At the present time, many AIDS clinical trials compare drug therapies by a time-to-event primary endpoint that measures the durability of suppression of HIV replication. For such studies, survival differences tend to occur early and/or late in the follow-up period due to drug differences in initial potency and/or durability of efficacy, and detecting these differences is of primary interest. We propose a weighted log-rank statistic that emphasizes early and/or late survival differences. We also consider some versatile tests that also emphasize these differences but are sensitive to a wider range of alternatives. The performances of the new tests are evaluated in numerical studies. For the alternatives of interest, the new tests show greater power and flexibility than commonly used weighted log-rank tests and related versatile tests. When the main interest is in detecting early and/or late survival differences, these tests may be preferable to the other versatile and weighted log-rank tests that have been studied.

Anti-HIV Agents↗