ORCID Profile
0000-0002-8052-9320
Current Organisations
Harvard Medical School
,
Brigham and Women's Hospital
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Publisher: Springer Science and Business Media LLC
Date: 07-02-2022
DOI: 10.1038/S41467-022-28252-5
Abstract: Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 in iduals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.
Publisher: Cold Spring Harbor Laboratory
Date: 09-2012
Abstract: Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
Publisher: Wiley
Date: 12-06-2017
Abstract: Nanofabrication using a "bottom-up" approach of hybrid electrode materials into a well-defined architecture is essential for next-generation miniaturized energy storage devices. This paper describes the design and fabrication of reduced graphene oxide (rGO) olyoxometalate (POM)-based hybrid electrode materials and their successful exploitation for asymmetric supercapacitors. First, redox active nanoclusters of POMs [phosphomolybdic acid (PMo
Publisher: Springer Science and Business Media LLC
Date: 09-2012
DOI: 10.1038/NATURE11247
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-2017
Abstract: High expression of the α-synuclein gene ( SNCA ) is a risk factor for Parkinson's disease (PD), but certain drugs may mitigate this risk. Mittal et al. ran a small-molecule screen to identify compounds that regulate levels of SNCA expression and found that several β2-adrenoreceptor (β2AR) agonists reduced them (see the Perspective by Snyder). These compounds modulated epigenetic marks at the SNCA gene, effectively suppressing SNCA transcription. The authors looked at the pharmaceutical history of more than 4 million Norwegians over an 11-year period and found a reduced risk of PD among those that were taking one of the β2AR agonists for other medical problems. Science , this issue p. 891 see also p. 869
Publisher: Cold Spring Harbor Laboratory
Date: 23-04-2020
DOI: 10.1101/2020.04.20.20073247
Abstract: Observational studies have identified correlations between environmental and lifestyle factors and Parkinson’s disease (PD). However, the causal direction of many of these relationships remains unclear. To infer causal relationships between smoking and alcohol intake and PD. We use a two-s le Mendelian randomization (MR) experimental design to infer causal relationships between smoking ( initiation, age of initiation, heaviness , and cessation ) and alcohol ( drinks per week ) consumption as exposure variables and PD as the health outcome. We also conduct sensitivity analyses, including testing for pleiotropic effects MR-Egger and MR-PRESSO, and multivariable MR to jointly model the effects of drinking and smoking behavior on PD risk. Both alcohol intake (OR = 0.69 95% CI 0.56-0.86 p=0.001). and smoking cessation (comparing current vs. former smokers ) (IVW OR = 0.39 95% CI 0.22 to 0.69 p=0.001) were causally associated with a reduced risk of PD. In addition, our multivariable MR results provide additional assurance that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior. Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers . Increased alcohol intake also had a protective effect over PD risk, and the alcohol dehydrogenase 1B ( ADH1B ) locus is a candidate for further investigating the mechanisms underlying this association.
Publisher: Public Library of Science (PLoS)
Date: 19-04-2011
Publisher: Springer Science and Business Media LLC
Date: 17-09-2018
Publisher: Oxford University Press (OUP)
Date: 16-12-2022
Abstract: Despite its association with severe health conditions, the etiology of sleep apnea (SA) remains understudied. This study sought to identify genetic variants robustly associated with SA risk. We performed a genome-wide association study (GWAS) meta-analysis of SA across five cohorts (NTotal = 523 366), followed by a multi-trait analysis of GWAS (multi-trait analysis of genome-wide association summary statistics [MTAG]) to boost power, leveraging the high genetic correlation between SA and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional and joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal = 1 477 352 Ncases = 175 522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. Our SA meta-analysis identified five independent variants with evidence of association beyond genome-wide significance. After adjustment for BMI, only one genome-wide significant variant was identified. MTAG analyses uncovered 49 significant independent loci associated with SA risk. Twenty-nine variants were replicated in the 23andMe GWAS adjusting for BMI. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. Our study uncovered multiple genetic loci associated with SA risk, thus increasing our understanding of the etiology of this condition and its relationship with other complex traits.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2018
DOI: 10.1038/S41593-018-0277-Z
Abstract: In the version of this article initially published, the legends for Supplementary Figs. 4-8 and 10-14 contained errors. The Supplementary Figure legends have been corrected in the HTML and PDF versions of the article.
Publisher: Cold Spring Harbor Laboratory
Date: 30-09-2020
DOI: 10.1101/2020.09.29.20199893
Abstract: Sleep apnoea is characterised by periods of halted breathing during sleep. Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied, and previous genetic analyses have not identified many robustly associated genetic risk variants. We performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (N Total =523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (N Total =1,477,352 N cases =175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method. Our MTAG analysis uncovered 49 significant independent loci associated with sleep apnoea risk. Twenty-nine variants were replicated in the 23andMe cohort. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions. Our study uncovered multiple genetic loci associated with sleep apnoea risk, thus increasing our understanding of the aetiology of this condition and its relationship with other complex traits.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1038/S41588-023-01428-5
Abstract: Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total s le size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach, which increased the number of independent risk loci to 312, with the vast majority replicating in a large independent cohort from 23andMe, Inc. (total s le size over 2.8 million 296 loci replicated at P 0.05, 240 after Bonferroni correction). Leveraging multiomics datasets, we identified many potential druggable genes, including neuro-protection targets likely to act via the optic nerve, a key advance for glaucoma because all existing drugs only target intraocular pressure. We further used Mendelian randomization and genetic correlation-based approaches to identify novel links to other complex traits, including immune-related diseases such as multiple sclerosis and systemic lupus erythematosus.
Location: United States of America
No related grants have been discovered for Xianjun Dong.