ArticleNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2019
An Exome-Wide Association Study Identifies New Susceptibility Loci for Age of Smoking Initiation in African- and European-American Populations.
Article in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Meta-analytic method reveal a significant association of theBDNF Val66Met variant with smoking persistence based on a large samples.The pharmacogenomics journal · 2020Pooled it
- Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.The Journal of pharmacology and experimental therapeutics · 2025Article
- Debiased lasso after sample splitting for estimation and inference in high-dimensional generalized linear models.The Canadian journal of statistics = Revue canadienne de statistique · 2025Article
- Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms.Frontiers in molecular neuroscience · 2022Article
- Prediction of Smoking Behavior From Single Nucleotide Polymorphisms With Machine Learning Approaches.Frontiers in psychiatry · 2020Article
- Tobacco Genomics: Complexity and Translational Challenges.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing an exome-wide association analysis.
methodsA total of 2510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels. After removal of those SNPs with a minor allele frequency (<0.01), 48091 and 34933 SNPs for AAs and EAs, respectively, were used to conduct a SNP-based association analysis. Gene-based analyses were then performed for all SNPs examined within each gene. Further, we estimated the proportion of variance explained by all common SNPs included in the analysis.
resultsThe strongest signals were detected for SNPs rs17849904 in the pitrilysin metallopeptidase 1 gene (PITRM1) in the AA sample (p = 9.02 × 10-7) and rs34722354 in the discoidin domain of the receptor tyrosine kinase 2 gene (DDR2) in the EA sample (p = 9.74 × 10-7). Both SNPs remained significant after Bonferroni correction for the number of SNPs tested. Subsequently, the gene-based association analysis revealed a significantly associated gene, DHRS7, in the AA sample (p = 5.00 × 10-6), a gene previously implicated in nicotine metabolism.
conclusionsOur study revealed two susceptibility loci for age of smoking initiation in the two ethnic samples, with the first being PITRM1 for AA smokers and the second DDR2 for EA smokers. In addition, we found DHRS7 to be a plausible candidate for ASI in the AA sample from our gene-based association analysis. IMPLICATIONS: PITRM1 and DHRS7 for African-American smokers and DDR2 for European-American smokers are new candidate genes for smoking initiation. These genes represent new additions to smoking initiation, an important but less studied phenotype in nicotine dependence research.
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