ArticleHuman molecular genetics2015
A multiancestry study identifies novel genetic associations with CHRNA5 methylation in human brain and risk of nicotine dependence.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.Molecular psychiatry · 2018Pooled it
- MeQTL analysis of childhood obesity links epigenetics with a risk SNP rs17782313 near MC4R from meta-analysis.Oncotarget · 2017Pooled it
- A cross-ancestry genetic atlas of shared susceptibility between infectious diseases and cancer.Functional & integrative genomics · 2026Article
- A trans-omics gene-smoking interaction study of lung cancer based on consortium data.American journal of respiratory and critical care medicine · 2026Article
- Multiple trait association analysis revealed common genetic loci between lung cancer and heart failure.Cardio-oncology (London, England) · 2026Article
- Integrative analysis of genetics, epigenetics and RNA expression data reveal three susceptibility loci for smoking behavior in Chinese Han population.Molecular psychiatry · 2024Article
- Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.Scientific reports · 2024Article
- An in-depth association analysis of genetic variants within nicotine-related loci: Meeting in middle of GWAS and genetic fine-mapping.Molecular and cellular neurosciences · 2023Article
- Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.Addiction (Abingdon, England) · 2023Article
- Investigation of the genetic effect of 56 tobacco-smoking susceptibility genes on DNA methylation and RNA expression in human brain.Frontiers in psychiatry · 2022Article
- Genetic architecture of four smoking behaviors using partitioned SNP heritability.Addiction (Abingdon, England) · 2021Article
- Article
- Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence.Frontiers in genetics · 2019Article
- Association and cis-mQTL analysis of variants in serotonergic genes associated with nicotine dependence in Chinese Han smokers.Translational psychiatry · 2018Article
- Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.European journal of human genetics : EJHG · 2018Article
- Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population.Translational psychiatry · 2018Article
- Human Genetics of Addiction: New Insights and Future Directions.Current psychiatry reports · 2018Review
- Estimating and testing direct genetic effects in directed acyclic graphs using estimating equations.Genetic epidemiology · 2018Article
- Time to first cigarette and serum cholesterol levels.Social science & medicine (1982) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Nicotine dependence is influenced by chromosome 15q25.1 single nucleotide polymorphisms (SNPs), including the missense SNP rs16969968 that alters function of the α5 nicotinic acetylcholine receptor (CHRNA5) and noncoding SNPs that regulate CHRNA5 mRNA expression. We tested for cis-methylation quantitative trait loci (cis-meQTLs) using SNP genotypes and DNA methylation levels measured across the IREB2-HYKK-PSMA4-CHRNA5-CHRNA3-CHRNB4 genes on chromosome 15q25.1 in the BrainCloud and Brain QTL cohorts [total N = 175 European-Americans and 65 African-Americans (AAs)]. We identified eight SNPs that were significantly associated with CHRNA5 methylation in prefrontal cortex: P ranging from 6.0 × 10(-10) to 5.6 × 10(-5). These SNP-methylation associations were also significant in frontal cortex, temporal cortex and pons: P ranging from 4.8 × 10(-12) to 3.4 × 10(-3). Of the eight cis-meQTL SNPs, only the intronic CHRNB4 SNP rs11636753 was associated with CHRNA5 methylation independently of the known SNP effects in prefrontal cortex, and it was the most significantly associated SNP with nicotine dependence across five independent cohorts (total N = 7858 European ancestry and 3238 AA participants): P = 6.7 × 10(-4), odds ratio (OR) [95% confidence interval (CI)] = 1.11 (1.05-1.18). The rs11636753 major allele (G) was associated with lower CHRNA5 DNA methylation, lower CHRNA5 mRNA expression and increased nicotine dependence risk. Haplotype analyses showed that rs11636753-G and the functional rs16969968-A alleles together increased risk of nicotine dependence more than each variant alone: P = 3.1 × 10(-12), OR (95% CI) = 1.32 (1.22-1.43). Our findings identify a novel regulatory SNP association with nicotine dependence and connect, for the first time, previously observed differences in CHRNA5 mRNA expression and nicotine dependence risk to underlying DNA methylation differences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.