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学者姓名：杨铁林
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| GB/T 7714 | Du, Mingfei , Wang, Yang , Gao, Wei -Hua et al. ASSOCIATION OF SERUM UROMODULIN AND GENETIC VARIANTS WITH BLOOD PRESSURE CHANGES, AND HYPERTENSION IN CHINESE ADULTS: RESULTS FROM TWO PROSPECTIVE COHORTS [J]. | JOURNAL OF HYPERTENSION , 2021 , 39 : E112-E112 . |
| MLA | Du, Mingfei et al. "ASSOCIATION OF SERUM UROMODULIN AND GENETIC VARIANTS WITH BLOOD PRESSURE CHANGES, AND HYPERTENSION IN CHINESE ADULTS: RESULTS FROM TWO PROSPECTIVE COHORTS" . | JOURNAL OF HYPERTENSION 39 (2021) : E112-E112 . |
| APA | Du, Mingfei , Wang, Yang , Gao, Wei -Hua , Sun, Yue , Zhang, Xiao -Yu , Zou, Ting et al. ASSOCIATION OF SERUM UROMODULIN AND GENETIC VARIANTS WITH BLOOD PRESSURE CHANGES, AND HYPERTENSION IN CHINESE ADULTS: RESULTS FROM TWO PROSPECTIVE COHORTS . | JOURNAL OF HYPERTENSION , 2021 , 39 , E112-E112 . |
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Genome-wide association studies (GWAS) have reproducibly associated the single nucleotide polymorphism (SNP) rs12454712 with waist-to-hip ratio adjusted for BMI (WHRadjBMI), but the functional role underlying this intronic variant is unknown. Integrative genomic and epigenomic analyses supported rs12454712 as a functional independent variant. We further demonstrated that rs12454712 acted as an allele-specific enhancer regulating expression of its located gene BCL2 by using dual-luciferase reporter assays and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Specifically, the rs12454712-C allele can bind transcription factor ZNF329, which efficiently elevates the enhancer activity and increases BCL2 expression. Knocking down Bcl2 in 3T3-L1 cells led to the downregulation of adipogenic differentiation marker genes and increased cell apoptosis. A significant negative correlation between BCL2 expression in subcutaneous adipose tissues and obesity was observed. Our findings illustrate the molecular mechanisms behind the intronic SNP rs12454712 for central obesity, which would be a potential and promising target for developing appropriate therapies.
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| GB/T 7714 | Dong, Shan-Shan , Zhu, Dong-Li , Zhou, Xiao-Rong et al. An Intronic Risk SNP rs12454712 for Central Obesity Acts As an Allele-Specific Enhancer To Regulate BCL2 Expression [J]. | DIABETES , 2021 , 70 (8) : 1679-1688 . |
| MLA | Dong, Shan-Shan et al. "An Intronic Risk SNP rs12454712 for Central Obesity Acts As an Allele-Specific Enhancer To Regulate BCL2 Expression" . | DIABETES 70 . 8 (2021) : 1679-1688 . |
| APA | Dong, Shan-Shan , Zhu, Dong-Li , Zhou, Xiao-Rong , Rong, Yu , Zeng, Mengqi , Chen, Jia-Bin et al. An Intronic Risk SNP rs12454712 for Central Obesity Acts As an Allele-Specific Enhancer To Regulate BCL2 Expression . | DIABETES , 2021 , 70 (8) , 1679-1688 . |
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Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 +/- 4.5 vs. 54.9 +/- 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 +/- 6.7 vs. 157.2 +/- 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
Keyword ：
gene polymorphism hypertension salt salt sensitivity uromodulin
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| GB/T 7714 | Du, Ming-Fei , Yao, Shi , Zou, Ting et al. Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions [J]. | JOURNAL OF CLINICAL HYPERTENSION , 2021 , 23 (10) : 1897-1906 . |
| MLA | Du, Ming-Fei et al. "Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions" . | JOURNAL OF CLINICAL HYPERTENSION 23 . 10 (2021) : 1897-1906 . |
| APA | Du, Ming-Fei , Yao, Shi , Zou, Ting , Mu, Jian-Jun , Zhang, Xiao-Yu , Hu, Gui-Lin et al. Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions . | JOURNAL OF CLINICAL HYPERTENSION , 2021 , 23 (10) , 1897-1906 . |
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The triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming. Here, we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from variant call format files. It is time and memory saving. In a test dataset with 100 SNPs from 60 000 subjects, it was at least 10.60 times faster and used only 0.03-13.33% of physical memory as compared with other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g. association P-values) and genomic region annotations. It can also compress the SVG files with a large number of SNPs and support subgroup analysis. This fast and convenient tool will facilitate the visualization of LD and haplotype blocks for geneticists.
Keyword ：
haplotype block linkage disequilibrium VCF files visualization
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| GB/T 7714 | Dong Shan-Shan , He Wei-Ming , Ji Jing-Jing et al. LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files. [J]. | Briefings in bioinformatics , 2021 , 22 (4) . |
| MLA | Dong Shan-Shan et al. "LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files." . | Briefings in bioinformatics 22 . 4 (2021) . |
| APA | Dong Shan-Shan , He Wei-Ming , Ji Jing-Jing , Zhang Chi , Guo Yan , Yang Tie-Lin . LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files. . | Briefings in bioinformatics , 2021 , 22 (4) . |
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BackgroundChildhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR).MethodsAfter data filtering, 263 adult traits genetically correlated with childhood BMI (P<0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI.ResultsWe identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (=-0.10, 95% CI -0.13 to -0.07, P=6.26x10(-11)). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR=1.09, 95% CI 1.06 to 1.11, P=4.28x10(-11)), essential hypertension (OR=1.12, 95% CI 1.08 to 1.16, P=1.27x10(-11)), type 2 diabetes (OR=1.36, 95% CI 1.30 to 1.43, P=1.57x10(-34)), and arthrosis (OR=1.09, 95% CI 1.06 to 1.12, P=8.80x10(-9)). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P>0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population.ConclusionsIn summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.
Keyword ：
Adult outcome Causal Childhood BMI Mendelian randomization
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| GB/T 7714 | Dong, Shan-Shan , Zhang, Kun , Guo, Yan et al. Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study [J]. | GENOME MEDICINE , 2021 , 13 (1) . |
| MLA | Dong, Shan-Shan et al. "Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study" . | GENOME MEDICINE 13 . 1 (2021) . |
| APA | Dong, Shan-Shan , Zhang, Kun , Guo, Yan , Ding, Jing-Miao , Rong, Yu , Feng, Jun-Cheng et al. Phenome-wide investigation of the causal associations between childhood BMI and adult trait outcomes: a two-sample Mendelian randomization study . | GENOME MEDICINE , 2021 , 13 (1) . |
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Abstract ：
Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH-dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics.
Keyword ：
dehydrogenase 6 (ND6) DNA methyltransferase 1 (DNMT1) insulin resistance mitochondrial dysfunction mitochondrial NADH‐ obesity and type 2 diabetes mellitus (T2DM)
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| GB/T 7714 | Cao, Ke , Lv, Weiqiang , Wang, Xueqiang et al. Hypermethylation of Hepatic Mitochondrial ND6 Provokes Systemic Insulin Resistance [J]. | ADVANCED SCIENCE , 2021 , 8 (11) . |
| MLA | Cao, Ke et al. "Hypermethylation of Hepatic Mitochondrial ND6 Provokes Systemic Insulin Resistance" . | ADVANCED SCIENCE 8 . 11 (2021) . |
| APA | Cao, Ke , Lv, Weiqiang , Wang, Xueqiang , Dong, Shanshan , Liu, Xuyun , Yang, Tielin et al. Hypermethylation of Hepatic Mitochondrial ND6 Provokes Systemic Insulin Resistance . | ADVANCED SCIENCE , 2021 , 8 (11) . |
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Corin, a transmembrane serine protease that can cleave pro-atrial natriuretic peptide (Pro-ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt-Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7-day low salt diet (3 g/day) and a 7-day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low-salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low-salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high-salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow-up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene-based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8-year follow-up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.
Keyword ：
blood pressure corin gene polymorphism salt salt sensitivity
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| GB/T 7714 | Zou, Ting , Yao, Shi , Du, Ming-Fei et al. Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults [J]. | JOURNAL OF CLINICAL HYPERTENSION , 2021 , 23 (12) : 2115-2123 . |
| MLA | Zou, Ting et al. "Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults" . | JOURNAL OF CLINICAL HYPERTENSION 23 . 12 (2021) : 2115-2123 . |
| APA | Zou, Ting , Yao, Shi , Du, Ming-Fei , Mu, Jian-Jun , Chu, Chao , Hu, Gui-Lin et al. Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults . | JOURNAL OF CLINICAL HYPERTENSION , 2021 , 23 (12) , 2115-2123 . |
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Aberrant telomerase reverse transcriptase (TERT) expression is crucial for tumor survival and cancer cells escaping apoptosis. Multiple TERT-locus variants at 5p15 have been discovered in association with cancer risk, yet the underlying mechanisms and clinical impacts remain unclear. Here, our association studies showed that the TERT promoter variant rs2853669 confers a risk of prostate cancer (PCa) in different ethnic groups. Further functional investigation revealed that the allele-specific binding of MYC and E2F1 at TERT promoter variant rs2853669 associates with elevated level of TERT in PCa. Mechanistically, androgen stimulations promoted the binding of MYC to allele T of rs2853669, thereby activating TERT, whereas hormone deprivations enhanced E2F1 binding at allele C of rs2853669, thus upregulating TERT expression. Notably, E2F1 could cooperate with AR signaling to regulate MYC expression. Clinical data demonstrated synergistic effects of MYC/E2F1/TERT expression or with the TT and CC genotype of rs2853669 on PCa prognosis and severity. Strikingly, single-nucleotide editing assays showed that the CC genotype of rs2853669 obviously promotes epithelial-mesenchymal transition (EMT) and the development of castration-resistant PCa (CRPC), confirmed by unbiased global transcriptome profiling. Our findings thus provided compelling evidence for understanding the roles of noncoding variations coordinated with androgen signaling and oncogenic transcription factors in mis-regulating TERT expression and driving PCa.
Keyword ：
AR signaling crpc E2F1 EMT MYC prostate cancer rs2853669 TERT
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| GB/T 7714 | Dong Xiaoming , Zhang Qin , Hao Jinglan et al. Large Multicohort Study Reveals a Prostate Cancer Susceptibility Allele at 5p15 Regulating TERT via Androgen Signaling-Orchestrated Chromatin Binding of E2F1 and MYC. [J]. | Frontiers in oncology , 2021 , 11 : 754206 . |
| MLA | Dong Xiaoming et al. "Large Multicohort Study Reveals a Prostate Cancer Susceptibility Allele at 5p15 Regulating TERT via Androgen Signaling-Orchestrated Chromatin Binding of E2F1 and MYC." . | Frontiers in oncology 11 (2021) : 754206 . |
| APA | Dong Xiaoming , Zhang Qin , Hao Jinglan , Xie Qianwen , Xu Binbing , Zhang Peng et al. Large Multicohort Study Reveals a Prostate Cancer Susceptibility Allele at 5p15 Regulating TERT via Androgen Signaling-Orchestrated Chromatin Binding of E2F1 and MYC. . | Frontiers in oncology , 2021 , 11 , 754206 . |
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Objective: Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. Methods: Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. Results: The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. Conclusions: This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.
Keyword ：
blood pressure gene polymorphism pregnancy-associated plasma protein-A2 salt salt sensitivity
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| GB/T 7714 | Wang, Yang , Jia, Hao , Gao, Wei-Hua et al. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults [J]. | JOURNAL OF HYPERTENSION , 2021 , 39 (9) : 1817-1825 . |
| MLA | Wang, Yang et al. "Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults" . | JOURNAL OF HYPERTENSION 39 . 9 (2021) : 1817-1825 . |
| APA | Wang, Yang , Jia, Hao , Gao, Wei-Hua , Zou, Ting , Yao, Shi , Du, Ming-Fei et al. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults . | JOURNAL OF HYPERTENSION , 2021 , 39 (9) , 1817-1825 . |
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Abstract ：
Since the bipolar disorder (BD) signals identified by genome-wide association study (GWAS) often reside in the non-coding regions, understanding the biological relevance of these genetic loci has proven to be complicated. Transcriptome-wide association studies (TWAS) providing a powerful approach to identify novel disease risk genes and uncover possible causal genes at loci identified previously by GWAS. However, these methods did not consider the importance of epigenetic regulation in gene expression. Here, we developed a novel epigenetic element-based transcriptome-wide association study (ETWAS) that tested the effects of genetic variants on gene expression levels with the epigenetic features as prior and further mediated the association between predicted expression and BD. We conducted an ETWAS consisting of 20 352 cases and 31 358 controls and identified 44 transcriptome-wide significant hits. We found 14 conditionally independent genes, and 10 genes that did not previously implicate with BD were regarded as novel candidate genes, such as ASB16 in the cerebellar hemisphere (P = 9.29 x 10(-8)). We demonstrated that several genome-wide significant signals from the BD GWAS driven by genetically regulated expression, and NEK4 explained 90.1% of the GWAS signal. Additionally, ETWAS identified genes could explain heritability beyond that explained by GWAS-associated SNPs (P = 5.60 x 10(-66)). By querying the SNPs in the final models of identified genes in phenome databases, we identified several phenotypes previously associated with BD, such as schizophrenia and depression. In conclusion, ETWAS is a powerful method, and we identified several novel candidate genes associated with BD.
Keyword ：
bipolar disorder candidate gene epigenetic regulation gene expression prediction missing heritability
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| GB/T 7714 | Yao, Shi , Wu, Hao , Liu, Tong-Tong et al. Epigenetic Element-Based Transcriptome-Wide Association Study Identifies Novel Genes for Bipolar Disorder [J]. | SCHIZOPHRENIA BULLETIN , 2021 , 47 (6) : 1642-1652 . |
| MLA | Yao, Shi et al. "Epigenetic Element-Based Transcriptome-Wide Association Study Identifies Novel Genes for Bipolar Disorder" . | SCHIZOPHRENIA BULLETIN 47 . 6 (2021) : 1642-1652 . |
| APA | Yao, Shi , Wu, Hao , Liu, Tong-Tong , Wang, Jia-Hao , Ding, Jing-Miao , Guo, Jing et al. Epigenetic Element-Based Transcriptome-Wide Association Study Identifies Novel Genes for Bipolar Disorder . | SCHIZOPHRENIA BULLETIN , 2021 , 47 (6) , 1642-1652 . |
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