Using Integrative Analysis of DNA Methylation and Gene Expression Data in Multiple Tissue Types to Prioritize Candidate Genes for Drug Development in Obesity.

Abstract:

:Obesity has become a major public health issue which is caused by a combination of genetic and environmental factors. Genome-wide DNA methylation studies have identified that DNA methylation at Cytosine-phosphate-Guanine (CpG) sites are associated with obesity. However, subsequent functional validation of the results from these studies has been challenging given the high number of reported associations. In this study, we applied an integrative analysis approach, aiming to prioritize the drug development candidate genes from many associated CpGs. Association data was collected from previous genome-wide DNA methylation studies and combined using a sample-size-weighted strategy. Gene expression data in adipose tissues and enriched pathways of the affiliated genes were overlapped, to shortlist the associated CpGs. The CpGs with the most overlapping evidence were indicated as the most appropriate CpGs for future studies. Our results revealed that 119 CpGs were associated with obesity (p ≤ 1.03 × 10-7). Of the affiliated genes, SOCS3 was the only gene involved in all enriched pathways and was differentially expressed in both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). In conclusion, our integrative analysis is an effective approach in highlighting the DNA methylation with the highest drug development relevance. SOCS3 may serve as a target for drug development of obesity and its complications.

journal_name

Front Genet

journal_title

Frontiers in genetics

authors

Guo Q,Zheng R,Huang J,He M,Wang Y,Guo Z,Sun L,Chen P

doi

10.3389/fgene.2018.00663

subject

Has Abstract

pub_date

2018-12-19 00:00:00

pages

663

issn

1664-8021

journal_volume

9

pub_type

杂志文章
  • Bayesian, Likelihood-Free Modelling of Phenotypic Plasticity and Variability in Individuals and Populations.

    abstract::There is a paradigm shift from the traditional focus on the "average" individual towards the definition and analysis of trait variation within individual life-history and among individuals in populations. This is a result of increasing availability of individual phenotypic data. The shift allows the use of genetic and...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00727

    authors: Filipe JAN,Kyriazakis I

    更新日期:2019-09-20 00:00:00

  • Revealing the Genetic Impact of the Ottoman Occupation on Ethnic Groups of East-Central Europe and on the Roma Population of the Area.

    abstract::History of East-Central Europe has been intertwined with the history of Turks in the past. A significant part of this region of Europe has been fallen under Ottoman control during the 150 years of Ottoman occupation in the 16-17th centuries. The presence of the Ottoman Empire affected this area not only culturally but...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00558

    authors: Bánfai Z,Melegh BI,Sümegi K,Hadzsiev K,Miseta A,Kásler M,Melegh B

    更新日期:2019-06-13 00:00:00

  • Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers.

    abstract::Thousands of DNA lesions are estimated to occur in each cell every day and almost all are recognized and repaired. DNA repair is an essential system that prevents accumulation of mutations which can lead to serious cellular malfunctions. Phenotypic evaluation of DNA repair activity of individuals is a relatively new a...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2014.00116

    authors: Slyskova J,Langie SA,Collins AR,Vodicka P

    更新日期:2014-05-23 00:00:00

  • Human migration, diversity and disease association: a convergent role of established and emerging DNA markers.

    abstract::With the gradual development of intelligence, human got curious to know his origin and evolutionary background. Historical statements and anthropological findings were his primary tool for solving the puzzles of his own origin, until came the golden era of molecular markers which took no time to prove it's excellence ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2013.00155

    authors: Guha P,Srivastava SK,Bhattacharjee S,Chaudhuri TK

    更新日期:2013-08-09 00:00:00

  • Little evidence of systemic and adipose tissue inflammation in overweight individuals(†).

    abstract:CONTEXT:The effect of weight loss by diet alone or diet in conjunction with exercise on low-grade inflammation in non-obese (overweight) individuals is not known. OBJECTIVE:Test the hypothesis that 24 weeks of moderate calorie restriction (CR; 25%) by diet only or with aerobic exercise would reduce markers of systemic...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2012.00058

    authors: Tam CS,Covington JD,Ravussin E,Redman LM,Pennington CALERIE Team.

    更新日期:2012-04-19 00:00:00

  • The Impact of CYP3A4*22 on Tacrolimus Pharmacokinetics and Outcome in Clinical Practice at a Single Kidney Transplant Center.

    abstract::Background: Although there is evidence that the CYP3A4*22 variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. Methods: In a cohort of 121 kidney transplant recipients, we analyzed the CYP3A4*1B, CYP3A4*22, and CYP3A5*3 allele...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00871

    authors: Abdel-Kahaar E,Winter S,Tremmel R,Schaeffeler E,Olbricht CJ,Wieland E,Schwab M,Shipkova M,Jaeger SU

    更新日期:2019-09-26 00:00:00

  • Six-lncRNA Immune Prognostic Signature for Cervical Cancer.

    abstract:Background:This study searched for immune-related long noncoding RNAs (lncRNAs) to predict the prognosis of patients with cervical cancer. Method:We obtained immunologically relevant lncRNA expression profiles and clinical follow-up data from cervical cancer patients from The Cancer Genome Atlas database and the Molec...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.533628

    authors: Chen Q,Hu L,Huang D,Chen K,Qiu X,Qiu B

    更新日期:2020-10-14 00:00:00

  • Phenome-wide association studies demonstrating pleiotropy of genetic variants within FTO with and without adjustment for body mass index.

    abstract::Phenome-wide association studies (PheWAS) have demonstrated utility in validating genetic associations derived from traditional genetic studies as well as identifying novel genetic associations. Here we used an electronic health record (EHR)-based PheWAS to explore pleiotropy of genetic variants in the fat mass and ob...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2014.00250

    authors: Cronin RM,Field JR,Bradford Y,Shaffer CM,Carroll RJ,Mosley JD,Bastarache L,Edwards TL,Hebbring SJ,Lin S,Hindorff LA,Crane PK,Pendergrass SA,Ritchie MD,Crawford DC,Pathak J,Bielinski SJ,Carrell DS,Crosslin DR,Ledbett

    更新日期:2014-08-05 00:00:00

  • Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel-Lindau Disease.

    abstract::Von Hippel-Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00867

    authors: Hong B,Ma K,Zhou J,Zhang J,Wang J,Liu S,Zhang Z,Cai L,Zhang N,Gong K

    更新日期:2019-09-18 00:00:00

  • Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis.

    abstract::Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important f...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2020.603552

    authors: Zhuang J,Huo Q,Yang F,Xie N

    更新日期:2020-10-29 00:00:00

  • Modeling the Metabolism of Arabidopsis thaliana: Application of Network Decomposition and Network Reduction in the Context of Petri Nets.

    abstract::Motivation:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpre...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2017.00085

    authors: Koch I,Nöthen J,Schleiff E

    更新日期:2017-06-30 00:00:00

  • Comprehensive RNA-Seq Data Analysis Identifies Key mRNAs and lncRNAs in Atrial Fibrillation.

    abstract::Long non-coding RNAs (lncRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression. However, the association between lncRNAs and atrial fibrillation (AF) is still not fully understood. In this study, we used RNA sequencing data to identify and quantify the both protein codi...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00908

    authors: Wu DM,Zhou ZK,Fan SH,Zheng ZH,Wen X,Han XR,Wang S,Wang YJ,Zhang ZF,Shan Q,Li MQ,Hu B,Lu J,Chen GQ,Hong XW,Zheng YL

    更新日期:2019-10-02 00:00:00

  • Predicting lncRNA-miRNA Interaction via Graph Convolution Auto-Encoder.

    abstract::The interaction of miRNA and lncRNA is known to be important for gene regulations. However, the number of known lncRNA-miRNA interactions is still very limited and there are limited computational tools available for predicting new ones. Considering that lncRNAs and miRNAs share internal patterns in the partnership bet...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00758

    authors: Huang YA,Huang ZA,You ZH,Zhu Z,Huang WZ,Guo JX,Yu CQ

    更新日期:2019-08-29 00:00:00

  • Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model.

    abstract::Binge drinking is a widespread problem linked to increased risk for alcohol-related complications, including development of alcohol use disorders. In the last decade, binge drinking has increased significantly, specifically in women. Clinically, sexually dimorphic effects of alcohol are well-characterized, however, th...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00567

    authors: Rhinehart EM,Nentwig TB,Wilson DE,Leonard KT,Chaney BN,Grisel JE

    更新日期:2018-11-29 00:00:00

  • GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation.

    abstract::Long non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insigh...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00488

    authors: Abou Alezz M,Celli L,Belotti G,Lisa A,Bione S

    更新日期:2020-05-15 00:00:00

  • Mediterranean Diet and Particulate Matter Exposure Are Associated With LINE-1 Methylation: Results From a Cross-Sectional Study in Women.

    abstract::Emerging evidence suggests that air pollution increases the risk of cardiovascular disease (CVD) and metabolic disorders, adding to the global burden of disease attributable to lifestyle and behavioral factors. Although long interspersed nucleotide elements 1 (LINE-1) methylation has been associated with these disorde...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00514

    authors: Barchitta M,Maugeri A,Quattrocchi A,Barone G,Mazzoleni P,Catalfo A,De Guidi G,Iemmolo MG,Crimi N,Agodi A

    更新日期:2018-10-30 00:00:00

  • IntAssoPlot: An R Package for Integrated Visualization of Genome-Wide Association Study Results With Gene Structure and Linkage Disequilibrium Matrix.

    abstract::Genome-wide association study (GWAS), exploring the historical and evolutionary recombinations at the population level, is a major method adopted to identify quantitative trait loci (QTL) for complex traits. However, to summarize GWAS results, gene structure, and linkage disequilibrium (LD) in a single view, multiple ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00260

    authors: He F,Ding S,Wang H,Qin F

    更新日期:2020-03-20 00:00:00

  • Estimation of Gene Expression at Isoform Level from mRNA-Seq Data by Bayesian Hierarchical Modeling.

    abstract::mRNA-Seq is a precise and highly reproducible technique for measurement of transcripts levels and yields sequence information of a transcriptome at a single nucleotide base-level thus enabling us to determine splice junctions and alternative splicing events with high confidence. Often analysis of mRNA-Seq data does no...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2012.00239

    authors: Bhattacharjee M,Gupta R,Davuluri RV

    更新日期:2012-11-27 00:00:00

  • Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry.

    abstract::Brugada syndrome (BrS) is a heritable disease that results in sudden cardiac death. In the exome/genomic era, certain reported pathogenic variants in some genetic diseases have been reclassified as benign owing to their high frequency in some ancestries. In the present study, we comprehensively reassessed all previous...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00680

    authors: Chen CJ,Lu TP,Lin LY,Liu YB,Ho LT,Huang HC,Lai LP,Hwang JJ,Yeh SS,Wu CK,Juang JJ,Antzelevitch C

    更新日期:2019-01-04 00:00:00

  • Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication.

    abstract::Cardiovascular diseases are a leading cause of morbidity and mortality in Western societies. It is now well established that microRNAs (miRNAs) are determinant regulators in various medical conditions including cardiovascular diseases. The recent discovery that miRNAs, while associated with different carriers, can be ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章,评审

    doi:10.3389/fgene.2013.00214

    authors: Kinet V,Halkein J,Dirkx E,Windt LJ

    更新日期:2013-11-12 00:00:00

  • Pan-Cancer Analysis Reveals the Functional Importance of Protein Lysine Modification in Cancer Development.

    abstract::Large-scale tumor genome sequencing projects have revealed a complex landscape of genomic mutations in multiple cancer types. A major goal of these projects is to characterize somatic mutations and discover cancer drivers, thereby providing important clues to uncover diagnostic or therapeutic targets for clinical trea...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00254

    authors: Chen L,Miao Y,Liu M,Zeng Y,Gao Z,Peng D,Hu B,Li X,Zheng Y,Xue Y,Zuo Z,Xie Y,Ren J

    更新日期:2018-07-17 00:00:00

  • Transcriptomes Divergence of Ricotia lunaria Between the Two Micro-Climatic Divergent Slopes at "Evolution Canyon" I, Israel.

    abstract::As one of the hotspot regions for sympatric speciation studies, Evolution Canyon (EC) became an ideal place for its high level of microclimatic divergence interslopes. In this study, to highlight the genetic mechanisms of sympatric speciation, phenotypic variation on flowering time and transcriptomic divergence were i...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00506

    authors: Qian C,Yan X,Yin H,Fan X,Yin X,Sun P,Li Z,Nevo E,Ma XF

    更新日期:2018-11-14 00:00:00

  • Detecting Diagnostic Biomarkers of Alzheimer's Disease by Integrating Gene Expression Data in Six Brain Regions.

    abstract::Alzheimer's disease (AD) is a neurodegenerative and progressive disease, which often causes irreversible damages to the cerebrum. The pathogenesis of AD is far from being fully understood, while there are some popular hypotheses. So far, the diagnosis of AD relies only on clinical screening in the form of imaging tech...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2019.00157

    authors: Wang L,Liu ZP

    更新日期:2019-03-12 00:00:00

  • Comparing Genomic Signatures of Selection Between the Abbassa Strain and Eight Wild Populations of Nile Tilapia (Oreochromis niloticus) in Egypt.

    abstract::Domestication to captive rearing conditions, along with targeted selective breeding have genetic consequences that vary from those in wild environments. Nile tilapia (Oreochromis niloticus) is one of the most translocated and farmed aquaculture species globally, farmed throughout Asia, North and South America, and its...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.567969

    authors: Nayfa MG,Jones DB,Benzie JAH,Jerry DR,Zenger KR

    更新日期:2020-10-15 00:00:00

  • Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities.

    abstract::Background: Milroy disease (MD) is rare and autosomal dominant resulting from mutations of the vascular endothelial growth factor receptor-3 (VEGFR-3 or FLT4), which leads to dysgenesis of the lymphatic system. Methods: Here we report a Chinese MD family with 2 affected members of two generations. We identified the mu...

    journal_title:Frontiers in genetics

    pub_type:

    doi:10.3389/fgene.2019.00206

    authors: Zhang S,Chen X,Yuan L,Wang S,Moli D,Liu S,Wu Y

    更新日期:2019-03-19 00:00:00

  • Characterization of Two Satellite DNA Families in the Genome of the Oomycete Plant Pathogen Phytophthora parasitica.

    abstract::Satellite DNA is a class of repetitive sequences that are organized in long arrays of tandemly repeated units in most eukaryotes. Long considered as selfish DNA, satellite sequences are now proposed to contribute to genome integrity. Despite their potential impact on the architecture and evolution of the genome, satel...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00557

    authors: Panabières F,Rancurel C,da Rocha M,Kuhn ML

    更新日期:2020-06-05 00:00:00

  • First High-Density Linkage Map and Single Nucleotide Polymorphisms Significantly Associated With Traits of Economic Importance in Yellowtail Kingfish Seriola lalandi.

    abstract::The genetic resources available for the commercially important fish species Yellowtail kingfish (YTK) (Seriola lalandi) are relative sparse. To overcome this, we aimed (1) to develop a linkage map for this species, and (2) to identify markers/variants associated with economically important traits in kingfish (with an ...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2018.00127

    authors: Nguyen NH,Rastas PMA,Premachandra HKA,Knibb W

    更新日期:2018-04-17 00:00:00

  • The Active Constituent From Gynostemma Pentaphyllum Prevents Liver Fibrosis Through Regulation of the TGF-β1/NDRG2/MAPK Axis.

    abstract::Liver fibrosis resulting from chronic liver damage constitutes a major health care burden worldwide; however, no antifibrogenic agents are currently available. Our previous study reported that the small molecule NPLC0393 extracted from the herb Gynostemma pentaphyllum exerts efficient antifibrotic effects both in vivo...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.594824

    authors: Huang H,Wang K,Liu Q,Ji F,Zhou H,Fang S,Zhu J

    更新日期:2020-11-04 00:00:00

  • PIANO: A Web Server for Pseudouridine-Site (Ψ) Identification and Functional Annotation.

    abstract::Known as the "fifth RNA nucleotide", pseudouridine (Ψ or psi) is the first-discovered and most abundant RNA modification occurring at the Uridine site, and it plays a prominent role in a number of biological processes. Thousands of Ψ sites have been identified within different biological contexts thanks to the advance...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00088

    authors: Song B,Tang Y,Wei Z,Liu G,Su J,Meng J,Chen K

    更新日期:2020-03-12 00:00:00

  • Exome Sequencing Analysis Identifies Rare Variants in ATM and RPL8 That Are Associated With Shorter Telomere Length.

    abstract::Telomeres are important for maintaining genomic stability. Telomere length has been associated with aging, disease, and mortality and is highly heritable (∼82%). In this study, we aimed to identify rare genetic variants associated with telomere length using whole-exome sequence data. We studied 1,303 participants of t...

    journal_title:Frontiers in genetics

    pub_type: 杂志文章

    doi:10.3389/fgene.2020.00337

    authors: van der Spek A,Warner SC,Broer L,Nelson CP,Vojinovic D,Ahmad S,Arp PP,Brouwer RWW,Denniff M,van den Hout MCGN,van Rooij JGJ,Kraaij R,van IJcken WFJ,Samani NJ,Ikram MA,Uitterlinden AG,Codd V,Amin N,van Duijn CM

    更新日期:2020-04-30 00:00:00