Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs
Open Access
- 3 April 2007
- journal article
- research article
- Published by Springer Nature in BMC Genomic Data
- Vol. 8 (1), 10
- https://doi.org/10.1186/1471-2156-8-10
Abstract
Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them.Keywords
This publication has 57 references indexed in Scilit:
- Novel genes identified in a high-density genome wide association study for nicotine dependenceHuman Molecular Genetics, 2006
- Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPsHuman Molecular Genetics, 2006
- Addiction molecular genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genesAmerican Journal Of Medical Genetics Part B-Neuropsychiatric Genetics, 2006
- Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholismAmerican Journal Of Medical Genetics Part B-Neuropsychiatric Genetics, 2006
- Molecular genetics of addiction vulnerabilityNeuroRX, 2006
- A genome‐wide screen for nicotine dependence susceptibility lociAmerican Journal Of Medical Genetics Part B-Neuropsychiatric Genetics, 2006
- Analysis of pooled DNA samples on high density arrays without prior knowledge of differential hybridization ratesNucleic Acids Research, 2006
- A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependenceAmerican Journal of Medical Genetics, 2003
- DNA Pooling: a tool for large-scale association studiesNature Reviews Genetics, 2002
- The Fagerström Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance QuestionnaireBritish Journal of Addiction, 1991