Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

ABSTRACT: Cigarette smoking is one of the largest causes of preventable death worldwide. Smoking behaviors, including age at smoking initiation (ASI), smoking dependence (SD), and smoking cessation (SC), are all complex phenotypes determined by both genetic and environmental factors as well as their interactions. To identify susceptibility loci for each smoking phenotype, numerous studies have been conducted, with approaches including genome-wide linkage scans, candidate gene-based association analysis, and genome-wide association study (GWAS). Therefore, we conducted an exome-wide association study to identify new susceptibility loci for the risk of nicotine dependence in European-American populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148812 | GEO | 2020/04/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in African-American Populations

Project description:Cigarette smoking is one of the largest causes of preventable death worldwide. Smoking behaviors, including age at smoking initiation (ASI), smoking dependence (SD), and smoking cessation (SC), are all complex phenotypes determined by both genetic and environmental factors as well as their interactions. To identify susceptibility loci for each smoking phenotype, numerous studies have been conducted, with approaches including genome-wide linkage scans, candidate gene-based association analysis, and genome-wide association study (GWAS). Therefore, we conducted an exome-wide association study to identify new susceptibility loci for the risk of nicotine dependence in African-American populations.

2020-04-10 | GSE148375 | GEO

Genome-wide DNA methylation differences in nucleus accumbens of smokers vs. nonsmokers

Project description:Cigarette smoking remains the leading cause of preventable death worldwide. Cigarette smoking behaviors (e.g., initiation, nicotine dependence, cessation) are heritable, and many genetic risk loci have been identified. However, the neurobiological mechanisms underlying the genetic risk loci along the trajectory of smoking are largely unknown. DNA methylation (DNAm) differences between smokers and nonsmokers can provide insight into mechanisms that predispose to smoking behaviors and consequences of the smoking exposure itself. Differential DNAm by smoking has been found at many CpG sites in blood, but because of the tissue specificity of gene regulation, differential DNAm that can only be detected in brain may have been missed. Here, we provide Illumina HumanMethylationEPIC array data generated in nucleus accumbens, an addiction-relevant brain tissue, from 221 deceased individuals: 53 current cigarette smokers, 168 nonsmokers. From these data, we have conducted an epigenome-wide association study (EWAS) and identified several CpG associations with smoking. A subset of the identified CpGs map to genes that were previously indicated as blood-based smoking DNAm biomarkers, but the other CpGs map to genes that were previously undetected in blood and may reflect brain-specific processes related to smoking.

2020-05-01 | GSE147040 | GEO

Genome-wide RNA-sequencing differences in nucleus accumbens of smokers vs. nonsmokers

Project description:Cigarette smoking remains the leading cause of preventable death worldwide. Cigarette smoking behaviors (e.g., initiation, nicotine dependence, cessation) are heritable, and many genetic risk loci have been identified. However, the neurobiological mechanisms underlying the genetic risk loci along the trajectory of smoking are largely unknown. RNA-sequencing (RNA-seq) differences between smokers and nonsmokers can provide insight into mechanisms that predispose to smoking behaviors and consequences of the smoking exposure itself. Here, we provide RNA-seq data generated in nucleus accumbens, an addiction-relevant brain tissue, from 223 deceased individuals: 50 current cigarette smokers, 171 nonsmokers, and 2 individuals with undetermined smoking status. DNA methylation data on the Illumina HumanMethylationEPIC array are also available on most of these individuals and made available (GEO accession number GSE147040).

2021-04-14 | GSE171936 | GEO

deCODE Genetics study on genes contributing to nicotine dependence in humans

Project description:A genome-wide association study on smoking behavior and nicotine dependence in Icelandic smokers, assessed by the number of cigarettes smoked per day, smoking initiation and degree of dependence on nicotine. The number of cigarettes smoked per day was ascertained through questionnaires given to individuals participating in multiple disease projects at deCODE Genetics (n=16,483). Smoking initiation was analyzed by comparing those that have ever smoked (n=16,483) versus those that have never smoked (n=21,667). The nicotine dependence analysis included 3,435 nicotine dependent cases (score 4 or higher on Fagerstrom Test for Nicotine Dependence (FTND) or endorsement of at least three of the seven Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria) and 3,344 low-quantity smokers as controls.

| phs000393.v1.p1 | EGA

An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

Project description:An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in European-American Populations

| PRJNA625893 | ENA

An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in African-American Populations

Project description:An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in African-American Populations

| PRJNA624118 | ENA

Expression data from monozygotic twins discordant for nicotine metabolism

Project description:The Nicotine Metabolic Ratio (NMR), the ratio of two stable metabolites of nicotine, cotinine and trans-3’hydroxycotinin, is a determinant of the number of cigarettes smoked per day (CPD), of smoking topography, responsiveness to treatment via transdermal nicotine for smoking cessation, and carcinogen activation and level. The predominant gene involved in nicotine metabolism is CYP2A6, a highly polymorphic locus located in a cluster of P450 cytochrome protein loci on chr19q13. A recent study comprehensively modeling CYP2A6 genetic variation at seven polymorphisms and a related Nicotine Metabolic Ratio, the cotinine: cotinine+nicotine ratio, explains 72% of NMRC/C+N variation. These results suggest that additional genes may be contributing to nicotine and cotinine metabolism directly or via interaction with CYP2A6 or other genes. To identify additional genes that may influence the NMR, we conducted a genome-wide gene expression analysis of lymphoblastoid cell line (LCL) gene expression in a sample of monozygotic twins discordant for the NMR.

2015-09-30 | GSE51284 | GEO

Nicotine Dependence GWAS Meta-Analysis

Project description:Nicotine dependence reduces the likelihood of quitting smoking and predicts withdrawal severity, treatment response, and smoking-related health outcomes. Nicotine dependence is a heritable trait (heritability estimates up to 75%), and prior genome-wide association study (GWAS) analyses have firmly established associations with DNA sequence variants in nicotine acetylcholine receptor genes on chromosome 15q25 and at other loci. In this GWAS meta-analysis, 15 independent studies were assembled for a total of 38,602 regular smokers (28,677 Europeans/European Americans and 9,925 African Americans) with nicotine dependence defined by the Fagerström Test for Nicotine Dependence (FTND). FTND scores, which range from 0 (no dependence) to 10 (highest dependence level), were used to categorize nicotine dependence as mild (scores 0-3), moderate (scores 4-6), or severe (scores 7-10). Two of the 15 studies additionally included low-intensity smokers who reported cigarettes per day as <10 but had no data available on the other FTND items and were defined as mildly dependent, given the high concordance rates between these FTND and CPD categories and minimal phenotype misclassification. The cross-ancestry GWAS meta-analysis tested nearly 18 million genotyped and 1000 Genomes-imputed SNPs/indels for association with mild/moderate/severe dependence. The well-known chromosome 15q25 locus was reconfirmed, and a novel chromosome 20q11 locus spanning the DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) gene was identified at genome-wide significance. Genome-wide results for the cross-ancestry and ancestry-specific GWAS meta-analyses are provided.

| phs001532 | dbGaP

Context-aware single-cell multiomics approach identifies cell-type specific lung cancer susceptibility genes

Project description:Genome-wide association studies (GWAS) identified over fifty genomic loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared multiome (transcriptome and chromatin accessibility map) of 117,911 human lung cells from ever- and never-smokers to profile context-specific gene regulation. We observed that most of differentially expressed genes based on smoking status (smoking-responsive genes) were cell-type specific, and inter-cellular communication strength for Major Histocompatibility Complex-I and -II pathways were inverted between ever- and never-smokers. Accessible chromatin peak detection identified candidate cis-regulatory elements (cCREs) from each lung cell type, and 37% of them were cell-type specific. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs prioritized the variants for 68% of the GWAS loci, a subset of which was also supported by transcription factor footprinting. cCRE colocalization and single-cell based trait relevance score nominated epithelial and immune cells as the main cell groups contributing to lung cancer susceptibility. Notably, cCREs of rare epithelial cell types, including AT2-proliferating (0.13%) and basal cells (1.8%), overlapped with CCVs from multiple GWAS loci. A multi-level cCRE-gene linking system identified candidate susceptibility genes from 57% of lung cancer loci, including smoking-responsive genes. Our multiome dataset identified lung cancer susceptibility genes that were not detected in previous tissue- or cell-line-based approaches and further revealed the cell types and contexts where the susceptibility genes are functional, including the interplay of epithelial and immune cell types even in a single locus.

2024-08-14 | GSE241468 | GEO

Cigarette Smoking Reduces DNA Methylation Levels at Multiple Genomic Loci but the Effect is Partially Reversible upon Cessation

Project description:DNA methylation is an epigenetic event whose pattern is altered frequently in a wide variety of human diseases. Smoking affects DNA methylation possibly leading to abnormal expression of a broad spectrum of genes which in turn may result to the various side effects and diseases associated with smoking. The long term effects of smoking have been widely studied but the mechanism(s) by which those effects may be reversible by smoking cessation are not clearly understood. Here, we conducted an epigenome-wide association study in peripheral-blood DNA in 464 individuals who were current, former and never-smokers. We identified 15 distinct loci (10 of which were novel) where DNA methylation was reduced in smokers and was reversed (but did not reach non-smoking levels) upon smoking cessation within 12 weeks. Although the functional impact of this reversal of DNA methylation is still not understood, this study illustrates the potential of epigenomics to provide insights into mechanisms of environmental and lifestyle exposures, and to suggest new avenues for clinical intervention

2014-11-25 | GSE50660 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data