ORCID Profile
0000-0002-6137-3391
Current Organisation
University of Queensland
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Publisher: Cold Spring Harbor Laboratory
Date: 06-12-2019
DOI: 10.1101/860767
Abstract: Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identified 143 independent loci in 112 1-Mb regions providing new insights into the physiology of vitamin D and implicating genes involved in (a) lipid and lipoprotein metabolism, (b) dermal tissue properties, and (c) the sulphonation and glucuronidation of 25OHD. Mendelian randomization models found no robust evidence that 25OHD concentration had causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes had (direct or indirect) causal effects on 25OHD concentration, clarifying the relationship between 25OHD status and health.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-08-2019
Abstract: We show that genotype-by-environment interaction can be inferred from an analysis without environmental data in a large s le.
Publisher: University of Queensland Library
Date: 2021
DOI: 10.14264/A4F8CEB
Publisher: Springer Science and Business Media LLC
Date: 08-11-2019
DOI: 10.1038/S41467-019-12653-0
Abstract: Accurate prediction of an in idual’s phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful in idual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. In simulation and cross-validation using 12 real traits and 1.1 million variants on 350,000 in iduals from the UK Biobank, SBayesR improves prediction accuracy relative to commonly used state-of-the-art summary statistics methods at a fraction of the computational resources. Furthermore, using summary statistics for variants from the largest GWAS meta-analysis ( n ≈ 700, 000) on height and BMI, we show that on average across traits and two independent data sets that SBayesR improves prediction R 2 by 5.2% relative to LDpred and by 26.5% relative to clumping and p value thresholding.
Publisher: American Society of Hematology
Date: 14-01-2016
DOI: 10.1182/BLOOD-2015-03-626671
Abstract: Wild-type AML1 and AML1/ETO form a complex on chromatin via binding to adjacent different motifs and interacting through the runt homology domain. The relative binding signals of AML1/ETO and AML1 and AP-1 recruitment determine whether AML1/ETO activates or represses its targets.
Publisher: Proceedings of the National Academy of Sciences
Date: 19-03-2013
Abstract: Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34 + cells, especially the LSC-enriched CD34 + CD38 − subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34 + cells but not those from normal CD34 + cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-κB and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide–down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.
Publisher: Cold Spring Harbor Laboratory
Date: 14-01-2019
DOI: 10.1101/519538
Abstract: Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large s le without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated in iduals of European ancestry for 13 quantitative traits in the UK Biobank, and identified 75 significant vQTLs with P .0×10 −9 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2020
DOI: 10.1038/S41467-020-15421-7
Abstract: Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identify 143 independent loci in 112 1-Mb regions, providing insights into the physiology of vitamin D and implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Mendelian randomization models find no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2021
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
DOI: 10.1038/S41467-021-21446-3
Abstract: Understanding how natural selection has shaped genetic architecture of complex traits is of importance in medical and evolutionary genetics. Bayesian methods have been developed using in idual-level GWAS data to estimate multiple genetic architecture parameters including selection signature. Here, we present a method (SBayesS) that only requires GWAS summary statistics. We analyse data for 155 complex traits (n = 27k–547k) and project the estimates onto those obtained from evolutionary simulations. We estimate that, on average across traits, about 1% of human genome sequence are mutational targets with a mean selection coefficient of ~0.001. Common diseases, on average, show a smaller number of mutational targets and have been under stronger selection, compared to other traits. SBayesS analyses incorporating functional annotations reveal that selection signatures vary across genomic regions, among which coding regions have the strongest selection signature and are enriched for both the number of associated variants and the magnitude of effect sizes.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2020
DOI: 10.1038/S41467-020-15587-0
Abstract: Promoter-anchored chromatin interactions (PAIs) play a pivotal role in transcriptional regulation. Current high-throughput technologies for detecting PAIs, such as promoter capture Hi-C, are not scalable to large cohorts. Here, we present an analytical approach that uses summary-level data from cohort-based DNA methylation (DNAm) quantitative trait locus (mQTL) studies to predict PAIs. Using mQTL data from human peripheral blood ( $$n = 1980$$ n = 1980 ), we predict 34,797 PAIs which show strong overlap with the chromatin contacts identified by previous experimental assays. The promoter-interacting DNAm sites are enriched in enhancers or near expression QTLs. Genes whose promoters are involved in PAIs are more actively expressed, and gene pairs with promoter-promoter interactions are enriched for co-expression. Integration of the predicted PAIs with GWAS data highlight interactions among 601 DNAm sites associated with 15 complex traits. This study demonstrates the use of mQTL data to predict PAIs and provides insights into the role of PAIs in complex trait variation.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2023
Location: Australia
No related grants have been discovered for Huanwei Wang.